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15 Important Questions and Answers About Dementia and Cognitive Impairment

Estimated reading time: 21 minutes

Dementia is a collective term for a decline in mental ability affecting memory, thinking, behavior, and emotion severely enough to interfere with daily life. 

Dementia represents a cluster of symptoms and should not, as such be, considered a disease.

 

One of the main challenges facing health professionals diagnosing and treating patients with dementia is to define the underlying cause or disease responsible for the patient’s symptoms. In fact, more than one hundred conditions may cause dementia. Alzheimer’s disease is the most common cause accounting for 60-70% of all cases.

Dementia ranges in severity. The mildest stage may be recognized by slight changes in thinking, remembering, and reasoning. In contrast, in the most severe stage, the patient must depend on others’ help for basic activities of living.

Although dementia becomes more common as people age, it should not be considered a normal part of aging. Many people live into their 90s and beyond without any signs of dementia (1).

Due to the aging of the population, the burden of dementia is increasing worldwide.

1. How Common Is Dementia?

Today, more people than before live longer and healthier lives. Hence, the world population has a higher proportion of older people. The fastest growth in the elderly population is taking place in China, India, and the southwestern part of Asia (2).

Worldwide, around 50 million people have dementia. Every year, there are nearly 10 million new cases.

The estimated proportion of the general population aged 60 and over with dementia is between 5-8% (2).

The total number of people with dementia is estimated to reach 82 million in 2030 and 152 million in 2050. Much of this increase is attributable to the increasing numbers of people with dementia living in low- and middle-income countries. Currently, 58% of people with dementia live in these countries. By 2050 this number will have risen to 68%.

Worldwide, around 50 million people have dementia. This number is estimated to reach 82 million in 2030 and 152 million in 2050. Much of this increase is attributable to the increasing numbers of people with dementia living in low- and middle-income countries.

2. What Are the Most Common Dementia Symptoms?

Dementia affects people differently, causing a considerable variation in symptoms between individuals.

Because of the gradual onset of symptoms, the early stage of dementia is often overlooked. Declining memory, especially short-term memory, is the most common early symptom. Other common symptoms include difficulties completing familiar tasks, losing track of time, and becoming lost in familiar places.

Interestingly, most patients with dementia do not by themselves complain of memory loss. It is often a spouse or another close relative who raises a concern (3).

During the next stage, the middle stage, forgetfulness becomes more pronounced. The patient may not remember recent events, and finding his way at home can become more difficult. A person may put things in unusual places, such as glasses in the fridge or a wristwatch in the sugar bowl. There may also be difficulties with communication. Wandering and repeated questioning becomes more prevalent. At this stage, the patient may need help with personal care.

Often there are difficulties with language, and finding the right words may become difficult.

During the late stage of dementia, memory loss usually worsens further. The patient may become unaware of time and place and can have difficulties recognizing relatives and friends. Behavior changes, including aggression, often become more pronounced. The patient may become anxious, suspicious, irritable, and agitated. Some patients may even become depressed or apathetic.

Sometimes passiveness is pronounced. The patient may sit in front of the television for hours, sleep more than usual, or appear to lose interest in hobbies.

3. What Are the Most Common Types of Dementia?

There are many different types of dementia. Alzheimer’s disease is the most common form of dementia and may contribute to 60–70% of cases.

Other major forms include vascular dementia, dementia with Lewy bodies (abnormal aggregates of protein that develop inside nerve cells), and a group of diseases that contribute to frontotemporal dementia (degeneration of the frontal lobe of the brain).

The boundaries between different forms of dementia are often unclear, and mixed forms exist. The term mixed dementia used to describe a combination of two or more types of dementia.

4. What Is Alzheimer’s Disease?

The science of Alzheimer’s disease has come a long way since 1906, when a German neurologist and psychiatrist named Dr. Alois Alzheimer first described the key features of the disease. Dr. Alzheimer noticed abnormal deposits in the brain of a 51-year old woman who had dementia.

Alzheimer’s disease is defined as a neurodegenerative disorder of uncertain cause that primarily affects older adults. It is the most common cause of dementia.

One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid plaques in the brain. Amyloid is a protein fragment that the body usually produces. In a healthy brain, these protein fragments are broken down and eliminated.

In Alzheimer’s disease, the amyloid fragments, particularly beta amyloid, accumulate to form hard, insoluble plaques.

Selective memory impairment is usually the earliest clinical manifestation of the disease. 

The diagnosis of is based on the patient’s history and tests of memory, problem-solving, attention, and language. Standard medical workup is necessary to assess the general health of the patient and to exclude other causes for Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) may be performed to support the diagnosis. 

Family history often plays a role. There is a higher risk of Alzheimer’s if a close family member has the disease. Having the ApoE4 genetic variant is one of the most significant risk factors for developing the disease (4).

Most cases of Alzheimer’s develop late in life, and most patients with the disease are 65 or older.

The risk of developing Alzheimer’s disease appears to be increased by many factors that affect the heart and blood vessels. These include high blood pressure, atherosclerotic heart disease, stroke, diabetes, and elevated cholesterol.  

So, although there’s no definitive way to prevent the disease, not smoking, keeping blood pressure and cholesterol at healthy levels,  regular exercise, maintaining a healthy weight, and eating healthy are all sensible measures.

Alzheimer’s disease is a progressive disorder, where dementia symptoms gradually worsen over several years. In its early stages, memory loss is mild, but with late-stage Alzheimer’s disease, individuals lose the ability to carry on a conversation and respond to their environment.

There is no cure available for Alzheimer’s disease. Although current treatments cannot stop the disease from progressing, they can temporarily slow the worsening of dementia symptoms and improve quality of life for those affected and their caregivers.

5. What Is Vascular Dementia?

Vascular dementia, also called vascular cognitive impairment (VCI), refers to any dementia that is primarily caused by cerebrovascular disease or impaired blood flow to the brain (5). It is the second most common cause of dementia, only exceeded by Alzheimer’s disease (6).

The symptoms of vascular dementia can vary widely, depending on the area of the brain affected by vascular injury. As in Alzheimer’s disease, memory loss is often pronounced.

Symptoms typical of cerebrovascular disease may often be present. Examples are difficulties with speech or walking and numbness or paralysis of one side of the face or body.

In many cases, a clinically diagnosed stroke appears to initiate the onset of symptoms. Hence the term poststroke dementia.

Multiple small strokes or vascular brain injuries may cause symptoms to occur more gradually. 

The risk factors for vascular dementia are the same as those for stroke. Not smoking, keeping blood pressure, blood sugar, and cholesterol within normal limits, healthy eating, exercise, and limiting alcohol consumption are examples of measures that may reduce the risk of vascular dementia.

6. What Is Dementia with Lewy Bodies (DLB)?

Dementia with Lewy bodies (DLB) may account for 10-15 percent of all cases of dementia (7). Hence it is a common type of dementia.

The disease is associated with abnormal deposits of a protein called alpha-synuclein in the brain. These deposits, called Lewy bodies, affect chemicals in the brain leading to dementia characterized by problems with thinking, movement, behavior, and mood (8). 

Lewy bodies are also found in the brains of patients with Parkinson’s disease.

In Parkinson’s disease, Lewy bodies are mainly found at the base of the brain, whereas in DLB, they tend to be found in the outer layers of the brain.

Diagnosing DLB may be challenging. Initially, the disease is often mistaken for Alzheimer’s disease. However, as the disease progresses, the patients usually develop symptoms typical of Parkinson’s disease. 

Parkinson’s disease is usually associated with tremor, stooped posture, slow movement, and shuffling gait.

Furthermore, patients with Parkinson’s disease often develop dementia. Hence, the term Parkinson’s disease dementia.

Dementia with Lewy bodies (DLB) may account for 10-15 percent of all cases of dementia. The disease is associated with abnormal protein deposits in the brain called Lewy bodies. Patients with DLB usually also develop symptoms typical of Parkinson’s disease.

 

7. What Is Frontotemporal Dementia (FTD)?

Frontotemporal dementia (FTD) occurs when nerve cells in the frontal and temporal lobes of the brain die, leading to shrinking of these parts of the brain.

Formerly known as Pick’s disease, the name, and classification of FTD has been a topic of discussion for decades (9). 

In fact, FTD is a group of heterogeneous neurodegenerative disorders characterized by noticeable changes in social behavior and personality or problems with language accompanied by degeneration of the frontal and/or temporal lobes (10).

Frontotemporal dementia (FTD) occurs when nerve cells in the frontal and temporal lobes of the brain die, leading to shrinking of these parts of the brain. FTD is a significant cause of dementia in younger people and is most often diagnosed between the ages of 45 and 65.

FTD is a significant cause of dementia in younger people and is is most often diagnosed between the ages of 45 and 65. 

The most common type of FTD is the behavioral variant, which is characterized by changes in personality and behavior.

Patients with the behavioral variant of FTD often lose their inhibitions and behave in socially inappropriate ways. They often lose interest and motivation and may show less sympathy or empathy. Their behavior may become repetitive, compulsive, and ritualized (11).

There may even be altered food preferences, such as carbohydrate cravings, particularly for sweet foods, and binge eating. Increased consumption of alcohol or tobacco may occur.

Primary progressive aphasia (PPA) is another clinical subtype of FTD.  In PPA, the early symptoms are dominated by difficulties with language that progressively get worse. These are manifested by deficits in word-finding, word usage, word comprehension, or sentence construction (12).

Three variants of PPA have been described based on the type of language impairment: nonfluent, semantic, and logopenic (13).

As FTD progresses, brain damage bends to become more widespread. As a result, the symptoms are often similar to those of the later stages of Alzheimer’s disease.

FTD is highly heritable. An autosomal dominant pattern of inheritance is observed in the families of approximately 10 to 25 percent of patients (12). An additional 40 percent of patients report a family history of dementia or psychiatric conditions.

8. How Is the Cause of Dementia Identified?

The first step when evaluating patients with suspected dementia is determining whether it is present or not. Several disorders may cause symptoms that mimic dementia, and these have to be excluded. Hence, a thorough medical evaluation of the patient should be performed at the first visit.

Cognitive and behavioral testing is the first step to assess if dementia is present. These tests can be divided into three levels of rigor: screening tools such as the Mini Mental State Examination (MMSE), an extended mental status examination, and formal neuropsychological testing (3).

However, although these tests help to assess the quantity of impairment, a detailed patient history, including an interview with a spouse or another close relative, is of crucial importance. 

Drug history is particularly important as many drugs can impair cognition.

All patients should be screened for depression. Cognitive impairment may sometimes be a key feature of depression. Furthermore, depression may often worsen cognitive impairment in patients with dementia.

Screening for B12 deficiency and hypothyroidism should be performed.

Neuroimaging with computed tomography (CT) or magnetic resonance (MR) may be helpful. In most cases, MRI is preferred over CT.

The use of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is an area of ongoing evaluation.

Symptoms of Parkinson disease may suggest dementia with Lewy bodies (DLB). Behavioral abnormalities and personality change in a relatively young patient may suggest the behavioral subtype of frontotemporal dementia (FTD). Language difficulties out of proportion to memory impairment suggest primary progressive aphasia (PPA).

9. What Conditions May Mimic Dementia?

Aging is associated with cognitive decline, usually consisting of mild changes in memory and the rate of information processing.

Most of us get more forgetful as we get older. We may sometimes struggle to remember names or put a signature to a face, and it may take a bit longer to find the right word. We may get distracted more easily or struggle to multi-task as well as we once did. 

These changes are normal, but they can be a nuisance and at times, frustrating. Many people worry that these things are an early sign of dementia

However, these deficits do not tend to be rapidly progressive, nor do they affect daily function as they would if dementia was present.

Nutritional deficiencies, side-effects from medications, and emotional distress can all produce symptoms that can be mistaken as early signs of dementia. These may include memory impairment and behavioral changes.

Patients with depression often show signs of cognitive impairment that may mimic dementia. Memory loss and an inability to focus or concentrate may be pronounced. Working memory, fluency, and planning and problem-solving abilities may be impaired (14).

Some drugs may interfere with cognitive function and cause symptoms that may mimic dementia.

10. Can Drugs Cause Cognitive Impairment Mimicking Dementia?

Yes, they can.

Anticholinergic drugs, in particular,  may negatively affect cognitive function. These include medications such as tolterodine, often used to treat urinary incontinence, some antidepressants,  antipsychotics, some heart medications, antispasmodics, antivertigo medications, and antiparkinsonian medications (15).

A recent study even showed that exposure to several types of potent anticholinergic drugs is associated with an increased risk of dementia (16).

Benzodiazepines, a class of medications used to treat anxiety or insomnia, comprise another group that has been linked with cognitive difficulties.

The frequently used cholesterol-lowering statins have been suspected of creating memory difficulties and mental slowing in some people. However, there is still divided in opinion on this issue. 

Cognitive changes associated with chemotherapeutic agents used to treat cancer have been documented. The condition is commonly called “chemo brain” or “chemo fog,” even though chemotherapy is unlikely the sole cause of these cognitive problems (17). The duration of chemo brain can vary from a few weeks to several years.

Pain killers, opioids, in particular, may negatively affect short-term memory.

11. What Is Mild Cognitive Impairment (MCI)?

Mild cognitive impairment (MCI) refers to cognitive impairment that is not severe enough to meet the criteria for dementia.

MCI is not an established diagnosis but refers to the transitional zone between normal aging and dementia (16). Although individuals with MCI have impaired cognitive function in specific domains, it is not severe enough to interfere with daily life.

However, it may be quite challenging to make the distinction between impairments that are normal for an adult and those that do represent MCI or dementia. What constitutes impairment in daily living is different for each individual (17).

MCI is relatively common. One study showed the following numbers for the prevalence of MCI (17):

  • 6.7% for ages 60-64,
  • 8.4% for 65-69,
  • 10.1% for 70-74,
  • 14.8% for 75-79,
  • 25.2% for 80-84.

The risk of developing dementia in individuals with MCI older than  65 years followed for 2 years was 14.9%. Thus it appears that people with MCI have an increased risk of developing dementia compared to the average population.

Amnestic MCI is the most common subtype of MICI and refers to individuals with significantly impaired memory who do not meet the criteria for dementia (18). Otherwise, cognitive function is preserved, and activities of daily living are intact.

Amnestic MCI is often regarded as a precursor to Alzheimer disease (19)

Nonamnestic MCI may affect a single domain or multiple domains other than memory. Examples of such domains are executive functioning, language, or visual-spatial skills. 

Low physical, mental and social activity appears to be associated with an increased risk of dementia

12. What Are the Risk Factors For Dementia?

Age is the strongest risk factor for dementia. The risk of Alzheimer disease increases rapidly after the age of 60 years. Overall, approximately 85 percent of dementia cases are in adults 75 years of age and older (20). 

Genetic factors play an important role in Alzheimer’s disease. Parental history of dementia is associated with a twofold increase in the risk of dementia. Risk estimates gradually decline with advancing parental age at diagnosis of dementia (21).

APOE genotype status is a powerful risk factor for subsequent risk of dementia (4).

Cardiovascular risk factors are linked to increased risk of dementia. One large study showed that midlife diabetes, hypertension, and smoking are associated with an increased risk of dementia (22).

In the same study, total cholesterol level was not associated with an increased hazard of dementia. Other lipid fractions were tested in separate models and were not related to the risk of dementia.

Stroke is a risk factor for dementia. Approximately 10 percent of patients develop new-onset dementia after a first stroke, and up to one-third of patients develop dementia after recurrent stroke (23).

Mild cognitive impairment (MCI) may be considered a risk factor for dementia because it often progresses to dementia.

Diabetes is associated with an approximately 1.5- to 2-fold increase in the relative risk of cognitive decline and dementia later in life (23).

Studies indicate that midlife obesity increases the risk of dementia later in life (23).

Obstructive sleep apnea (OSA) has been associated with an increased risk for MCI and dementia. A very large pooled analysis showed that those with sleep-disordered breathing were 26 percent more likely to develop clinically relevant cognitive decline or dementia (24).

Low physical, mental, and social activity appears to be associated with an increased risk of dementia. Because these are all are modifiable factors, they may present options for decreasing the risk of cognitive decline and dementia.

Lower levels of education are associated with an increased risk of dementia (25).

Alcohol abuse is associated with increased risk of cognitive decline and dementia.

13. How Is Dementia Treated?

It is true for almost all of the diseases causing dementia that they cannot be cured.

Non-drug treatments of dementia mainly play a supportive role. 

Cognitive rehabilitation aims to help patients in the early stages of dementia to maintain memory and cognitive function. 

There is promising evidence that exercise programs may improve the ability to perform activities of daily life in people with dementia (26). 

Other popular activities include music, singing, or art. It is vital that people with dementia stay as active as they can, physically, mentally, and socially. Taking part in meaningful activities is enjoyable and leads to increased confidence and self-esteem (27).

There are drugs available that may reduce the symptoms of dementia and possibly halt progression for a while. Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine are frequently used for this purpose. These drugs appear to provide modest symptomatic benefit in some patients with dementia (28).

Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The drug which may protect brain cells and appears to have modest benefits in patients with moderate to severe Alzheimer’s disease. (28). There is little, if any, evidence that patients with milder disease derive benefit from the drug.

14. What Is the Prognosis of Patients With Dementia?

Dementia shortens life expectancy. Irrespective of the underlying cause, dementia is a progressive disorder.

The rate of progression for Alzheimer’s disease varies widely. The average life expectancy after the disease is diagnosed  has been reported to be between 8 and 10 years but may range from 3 to 20 years (29). The degree of impairment at diagnosis will affect life expectancy.

The average life expectancy after a the disease is diagnosed has been reported to be between 8 and 10 years but may range from 3 to 20 years.

Older age of onset Alzheime’s symptoms is associated with a slower rate of decline compared with younger patients (30).

Like all other types of degenerative dementia, dementia with Lewy bodies (DLB) is a progressive disorder and associated with a shortened lifespan. Cognitive impairment and Parkinson symptoms both tend to worsen over time.

In general, the prognosis of DLB is similar to Alzheimer’s disease. However, in some patients, symptoms may progress faster and slower in others (31). 

Early survival analyses showed median survival from diagnosis of frontotemporal dementia (FTD) to be 7–13 years in clinic cohorts (32). The behavioral type and primary progressive aphasia (PPA show comparable survival times. Survival is usually worse if concomitant motor neuron disease is present.

15. How Can dementia Be Prevented?

Seven modifiable risk factors have been associated with increased risk of Alzheimer’s disease (33).

  • Diabetes
  • Midlife hypertension
  • Midlife obesity
  • Depression
  • Physical inactivity
  • Smoking
  • Cognitive inactivity or low educational attainment

It has been estimated that up to half of cases are potentially attributable to these modifiable risk factors.

Avoiding these factors may markedly reduce the risk of dementia.

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Why and How To Lower Triglycerides in People at Risk of Heart Disease

Estimated reading time: 11 minutes

Triglycerides are important organic compounds. Most of the fat we consume in our diet is triglyceride and so is most of the fat we store in our body.

Fatty acids contained in triglycerides are an essential source of energy for human cells.

Triglyceride concentration can be measured in blood and may provide valuable information about metabolism and general health. High levels may reflect underlying metabolic disorders and evidence shows that high blood triglycerides are associated with increased risk of heart disease (1,2,3).

However, association only means that there is a correlation between two or more variables. In this case, the higher the blood triglycerides, the higher the risk of developing heart disease.

Hence, discovering an association between variables does not prove a causative relationship. Here, a correlation between triglyceride levels and the risk of heart disease does not prove that triglycerides cause heart disease. Nor does it prove that lowering them will prevent disease.

Interestingly, when it comes to assessing the risk of cardiovascular disease, triglycerides have always played second fiddle to cholesterol.

As a result, dietary advice for people with heart disease usually aims at lowering blood cholesterol, particularly LDL-cholesterol. Targeting LDL- cholesterol has become common practice.

Therefore, replacing saturated fat with polyunsaturated and monounsaturated fats, and increasing the intake of food products rich in fiber and complex carbohydrates such as whole grains, is usually recommended.

Interestingly, it may be tricky to address triglycerides at the same time as LDL cholesterol. The reason is that a diet that lowers LDL cholesterol may raise triglycerides and vice versa. For example, low-fat diets may lower LDL cholesterol but are less effective in lowering triglycerides compared to low-carbohydrate diets (4).

Another reason why main stream medicine has tended to ignore triglycerides is that the pharmaceutical industry has shown limited interest in developing drugs that influence triglycerides. However, this may have changed recently with the publication of the highly important REDUCE-IT trial (5).

Triglyceride-Rich Lipoproteins

High blood levels of triglycerides are most often associated with high levels of the two most important triglyceride-rich lipoproteins; chylomicrons and very low density lipoproten (VLDL).

The main role of these lipoproteins is to transport triglycerides and other types of lipids, such as cholesterol, in the circulation.

Triglycerides are composed of three molecules of fatty acids attached to a glycerol molecule.

Chylomicrons are formed in the intestine after a meal. They contain triglycerides and small amounts of cholesterol.

Chylomicrons are subsequently broken down by an enzyme called lipoprotein lipase into free fatty acids that are utilized for energy production by the heart and skeletal muscles or stored in fat (adipose) tissue.

The chylomicron remnants are then removed from the circulation by liver cells.

VLDL is produced by liver cells. It transports both triglycerides and cholesterol. Once in the circulation, VLDL is broken down by lipoprotein lipase in capillary beds, releasing triglycerides for energy utilization by cells or storage in adipose tissue.

The composition of VLDL changes when triglycerides have been released. VLDL then becomes becomes intermediate-density lipoprotein (IDL). Later, when the amount of cholesterol increases, IDL becomes low-density lipoprotein (LDL).

Triglyceride-Rich Lipoproteins Are Associated With Inflammation and Atherosclerosis

Triglyceride rich lipoproteins are associated with inflammation and increased atherosclerosis (6).

High levels of chylomicrons increase the risk of acute pancreatitis, an inflammation of the pancreas. Chylomicron and VLDL remnants increase inflammation of the endothelium (the innermost layer of the artery).

Chylomicron remnants and VLDL remnants have been shown to rapidly penetrate the arterial wall and promote atherosclerosis (7).

Recent data suggests that VLDL cholesterol or remnant cholesterol is a stronger promoter of atherosclerosis than LDL cholesterol (8).

Definition of Normal and High Levels of Triglycerides

Blood levels of triglycerides are stratified according to population data and their associated risk of coronary artery disease.

In the USA, triglycerides are measured in mg/dL but in Australia, Canada, and most European countries they are measured in mmol/L.

To convert from mg/dL to mmol/L, divide by 88.5

Here is how triglyceride levels are looked at in terms of cardiovascular risk:

Normal: <150 mg/dL (1.7 mmol/L)

Borderline high: 150 to 199 mg/dL (1.7 to 2.2 mmol/L)

High: 200 to 499 mg/dL (2.3 to 5.6 mmol/L)

Very high: ≥500 mg/dL (≥5.7 mmol/L)

The term hypertriglyceridemia is used to describe high blood levels of triglycerides.

Hypertriglyceridemia is a relatively common disorder. In the United States, 33 percent of adults have triglyceride levels above 150 mg/dl (1.7 mmol/L) and 18 percent have levels above 200 mg/dl (2.3 mmol/L)(9).

Fasting and Non-Fasting Levels of Triglycerides

Following a fatty meal, blood levels of triglycerides will rise. Hence, raised blood triglycerides following a meal (postprandial hypertriglyceridemia) are caused by chylomicrons produced in the intestine.

Chylomicrons disappear from the circulation soon after the triglycerides have been delivered to the tissues.

Moderate fasting hypertriglyceridemia is usually due to increased VLDL production by the liver. This is often a result of excessive carbohydrate intake.

Triglycerides may also become elevated with obesity, physical inactivity, smoking, diseases such as diabetes and renal failure, drugs such as estrogen, tamoxifen and corticosteroids, and genetic disorders (familial hypertriglyceridemia, familial combined hyperlipidemia, and familial dysbetalipoproteinemia).

There are several types of familial hypertriglyceridemia. These disorders are associated with increased risk of coronary artery disease (10) which appears independent of cholesterol levels (11).

Serum triglyceride values above 1000 mg/dL (11 mmol/L) are rare (less than 1/5000 individuals). The serum in these patients is opalescent due to an increase in VLDL or milky due to elevated chylomicrons.

Triglycerides and Cardiovascular Disease

Despite evidence that chylomicron and VLDL remnants promote atherosclerosis, the importance of lowering triglycerides has so far not been considered a priority for patients with coronary heart disease.

However, several conditions associated with high triglycerides, such as insulin resistance, a preponderance of small LDL particles, and low HDL- cholesterol, may play an important role in the development of atherosclerosis.

Reduced activity of lipoprotein lipase, which is common in insulin resistance, may slow the clearance of triglyceride-rich lipoproteins from the circulation.

VLDL remnants may enter the vessel wall or be converted to small LDL particles. Small LDL particles tend to circulate for a longer duration where they become susceptible to oxidation, glycation, and glyco-oxidation leading to increased risk of atherosclerosis.

Small dense LDL particles appear more strongly associated with the risk of cardiovascular events than larger particles (12,13). 

In the so-called SCRIP trial, high triglyceride levels were associated small, dense particles in 90 percent of subjects whereas lower triglyceride levels were associated with larger buoyant particles in 90 percent of subjects (14).

Recent genetic studies have addressed the relationship between triglyceride-rich lipoproteins and the risk of cardiovascular events. The results of one of these studies imply that the elevated cholesterol content of triglyceride-rich lipoprotein particles may cause coronary heart disease (15).

Another study found that a genetic mutation associated with low blood levels of triglycerides was associated with less risk of cardiovascular disease (16).

These studies strongly support the hypothesis that high blood levels of triglycerides may increase the risk of cardiovascular disease and that low levels may be protective.

The REDUCE-IT Trial – A Landmark Cardiovascular Study

The results of the REDUCE-IT trial were recently published in the New England Journal of Medicine and The Journal of the American College of Cardiology) (5,17).

The study randomized 8,179 statin-treated patients with triglycerides ≥135 and <500 mg/dL and LDL-cholesterol >40 and ≤100 mg/dL , and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4g/day or placebo.

Icosapent ethyl is a highly purified and stable EPA ethyl ester that has been shown to lower triglyceride levels.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two most common long chain n-3 polyunsaturated fatty acids (PUFAs) in fish oil. Both are omega-3 fatty acids.

The primary cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or unstable angina, for icosapent ethyl vs. placebo, was 17.2% vs. 22.0%. The absolute risk reduction of 4.8% is highly significant.

Triglyceride levels were lowered at one year by 39.0 mg/dl vs. 4.5 mg/dl on on icosapent ethyl vs. placebo. LDL cholesterol was lowered by 2 mg/dl vs. 7 mg/dl.

The rate of cardiovascular death was 9.6% vs 12.4 % on icosapent ethyl vs. placebo which is statistically significant. All-cause mortality was 6.7% vs. 7.6%, which is not statistically significant.

The risk of atrial fibrillation/flutter was 5.3% vs 3.9% and the risk of serious adverse bleeding was 2.7% vs. 2.1% on icosapent ethyl vs. placebo

Why Is the REDUCE-IT Trial so Important?

The large number of important ischemic events averted with icosapent ethyl, including a significant reduction in fatal and nonfatal stroke (28%), cardiac arrest (48%), sudden death (31%), and cardiovascular death (20%), is indicative of a very favorable risk- benefit profile

Although several mechanisms may explain the efficacy of the drug it has to be assumed that the lowering of blood triglycerides is the most important.

The study results are in stark contrast to cardiovascular outcome studies with other agents that lower triglyceride levels and with low-dose omega-3 fatty acid mixtures, where cardiovascular outcome benefit has not been consistently observed in statin-treated patients (17).

The distinction of the cardiovascular benefits observed in REDUCE-IT from the lack of cardiovascular benefits observed in statin-treated populations with add-on omega-3 fatty acid mixtures may likely be due to the high EPA levels.

EPA has unique lipid and lipoprotein, anti-inflammatory, anti-platelet, anti-thrombotic, and cellular modifying effects.

REDUCE-IT is the first trial to show that lowering triglycerides without affecting LDL-cholesterol significantly improves clinical outcome in high risk patients.

With the rapidly increasing prevalence of central obesity and metabolic syndrome , targeting triglycerides me even become more important in the near future.

Whether targeting triglycerides by dietary measures will improve cardiac outcome remains to be proven.

However, it would be naive to believe that dietary measures that tend to lower triglycerides are less important than those intended to lower LDL-cholesterol.

The Management of High Triglycerides

Non-Pharmacological Therapy

Lifestyle modification is the first-line therapy for people with elevated triglycerides.

Many individuals with high triglycerides have insulin resistance and metabolic syndrome. In these cases, hypertriglyceridemia is often associated with visceral obesity low levels of HDL cholesterol, high blood pressure and type 2 diabetes.

In mild to moderate hypertriglyceridemia, losing weight and reducing carbohydrate intake (especially high glycemic index foods and high fructose foods) can lower VLDL and triglycerides.

For these patients, weight loss, regular physical exercise, and avoidance of added sugars (18) are all important. Other risk factors such as smoking and high blood pressure should also be addressed (19).

Fatty acids used by the liver to produce VLDL are derived mainly from two sources.

Firstly, during conditions such as obesity, diabetes, and insulin resistance, there is increased fatty acid flux from adipose tissue to the liver. Secondly, there is an increased de novo synthesis of fatty acids in the liver mainly from carbohydrates.

For this reason, in mild to moderate hypertriglyceridemia, losing weight and reducing carbohydrate intake (especially high glycemic index foods and high fructose foods) can lower VLDL and triglycerides.

Dietary fat is not a significant source of liver triglyceride (20), and high fat diets usually don’t raise fasting triglycerides.

The situation may be different in more severe hypertriglyceridemia (above 500 to 1000 mg/dL (5.6 to 11.3 mmol/L)), where the clearance of chylomicrons becomes very slow. Under these circumstances, it is crucial to reduce dietary fat intake to lower triglycerides.

It is necessary for patients with severe hypertriglyceridemia to avoid alcohol abuse as it can cause substantial increases in triglyceride levels and cause acute pancreatitis.

Pharmacological Therapy

Several drugs are used for the management of hypertriglyceridemia.

Although statins are not very effective for lowering triglycerides per se, they are often used to reduce the risk of cardiovascular events in patients with hypertriglyceridemia.

One of the most commonly used drug to lower triglycerides is gemfibrozil (21).

Gemfibrozil belongs to a group of drugs called fibrates which lower triglycerides by increasing the synthesis of lipoprotein lipase which increases the clearance of triglycerides. 

Fibrate therapy with either fenofibrate or gemfibrozil can reduce triglyceride levels by 20 to 50 percent. In severe hypertriglyceridemia, gemfibrozil may lower triglycerides as much as 70 percent (22).

In the Helsinki Heart Study, a clinical benefit of gemfibrozil therapy was found in the group with a triglyceride level >201 mg/dL (2.3 mmol/L) and an LDL-C/HDL-C ratio >5.0 (23).

The VA-HIT trial assessed the efficacy of gemfibrozil in patients with low HDL cholesterol, relatively low LDL cholesterol, and mild to moderate hypertriglyceridemia (24). Gemfibrozil raised HDL cholesterol by 6 percent, lowered triglycerides by 31 percent, but had no significant effect on LDL cholesterol. At five years, there was an absolute risk reduction of 4.4 percent with gemfibrozil.

In the ACCORD Lipid trial, fenofibrate improved outcomes in type 2 diabetes in a subset of patients with elevated triglyceride levels and low HDL cholesterol (25).

Nicotinic acid at doses of 1500 to 2000 mg daily can reduce triglyceride levels by 15 to 25 percent (26). However, studies supporting a clinical efficacy of nicotinic acid are lacking. There is data suggesting worsening of glycemic control when nicotinic acid is administered to patients with type 2 diabetes (27).

The AIM-HIGH trial studied the addition of nicotinic acid to statin therapy in patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg/dL (1.81 mmol/L)(28). 

There was no incremental clinical benefit from the addition of nicotinic acid during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.

Intake of fish oil (29) can lower blood triglycerides by as much as 50 percent (30). Relatively high doses of omega-3 fatty acids (EPA + DHA) are needed to achieve this effect (up to 3-4 g/day).

Lovasa (Omecor) and icosapent ethyl (Vascepa) are commercial preparations of omega-3 fatty acids that can lower blood triglycerides by as much as 45 percent (31,32).

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Air Travel and Venous Thromboembolism (VTE) – Who’s at Risk and What Can Be Done?

One of the most feared adverse health effects of civil aviation is the formation of blood clots in the deep veins of the lower limb, usually called deep vein thrombosis (DVT).

A part of the clot can break off and travel through the bloodstream to the lungs, causing pulmonary embolism (PE) which is a serious medical condition. Venous thromboembolism (VTE) refers to DVT, PE, or both (1)

In general, the chances of developing DVT are about 1 in 1000 per year. The cumulative chance of developing DVT over a lifetime ranges from 2 to 5 percent (2).

But what about air travel? Is it true that flying long distance can increase the risk of VTE? And, if true, what measures can be taken to reduce the risk?

Civil aviation has seen a steady increase in the number of air travelers during the last decade.

There are about 5.000 aircraft in the sky at any given time, and the number of average daily scheduled passenger flights worldwide is approximately 26.500. In 2016, the number of scheduled passenger flights was 9.7 million (3).

More than 2.5 million domestic and international passengers fly every day. The estimated number of air travelers in 2016 was 3.6 billion. That’s about 800 million more than in 2011 (4).

The term ‘economy class syndrome’ refers to the occurrence of thrombotic events during long-haul flights, mainly in economy class passengers (5).

With the aging of the population, and the increasing number of travelers with acute or chronic illnesses we might see an increase in flight-related VTE in the next few years.

What is Venous Thromboembolism (VTE)?

VTE refers to a blood clot that starts in a vein. It is the third leading vascular diagnosis, secondary to heart attack and stroke, affecting between 300,000 to 600,000 Americans each year (6).

Two clinical entities are associated with VTE; deep vein thrombosis (DVT) and pulmonary embolism (PE)

DVT is a blood clot in a deep vein, usually in the leg.

PE occurs when a DVT clot breaks free from a vein wall, travels to the lungs and then blocks some or all of the blood supply.

VTE can affect anyone but this risk is higher if certain risk factors are present.

The factors that increase the risk of VTE include a history of a recent major general or orthopedic surgery, recent fracture of the pelvis, hip bones or long bones of the lower limb, multiple trauma and lower-extremity paralysis due to spinal cord injury.

The presence of cancer increases the risk of VTE. Chemotherapy and surgery for cancer further increase the risk (7).

Other factors associated with increased risk of VTE include age, prior history of VTE, obesity, prolonged immobility, the use of oral contraceptives or estrogen treatment for menopause symptoms, and genetic conditions that affect blood clotting.

VTE refers to a blood clot that starts in a vein. Two clinical entities are associated with VTE; deep vein thrombosis (DVT) and pulmonary embolism (PE). Certain risk groups are at increased risk of VTE.

What’s the Difference Between Venous Thromboembolism (VTE) and Arterial Thrombosis?

It is very important to differentiate between VTE and arterial thrombosis.

Arterial thrombosis is a blood clot that develops in an artery. It can obstruct or stop the flow of blood to major organs, such as the heart or brain.

If a blood clot blocks a coronary artery (the arterlies supplying the heart muscle with blood), it will cause a heart attack. If it blocks an artery in the brain, it will cause a stroke.

Hence, symptoms depend on where the blood clot has formed.

An arterial embolism is a blood clot that has broken free and traveled through the arteries and become stuck. An arterial embolus can block or restrict blood flow to an organ or a limb.

There is no evidence that flying increases the risk of arterial thrombosis or arterial embolism. Hence, it has not bee shown that flying increases the risk of heart attack or stroke.

Arterial thrombosis is a blood clot that develops in an artery. Hence, it is a different phenomenon than VTE. It has not been shown that flying increases the risk of arterial thrombosis.

Does Flying Increase the Risk of Venous Thromboembolism (VTE)?

It is difficult to analyze the relationship between VTE and air travel. The main reason is that symptoms may not occur for several days after flying. Hence, a cause-and-effect relationship may be hard to establish.

However, there does appear to be a relationship between flight duration and the subsequent occurrence of VTE (8). The risk is greatest within the first two weeks but may be present for up to eight weeks after travel (9).

It has been estimated that the risk of VTE is approximately 2- to 4-fold increased after air travel (10). It rises with increasing flight exposure and in certain high-risk groups.

One study reported that the incidence of symptomatic VTE is 0.5 percent (one in every 4.500 flights) for flights longer than 12 hours (11).

The absolute risk is much higher if asymptomatic DVT is included and one study suggests that symptomless DVT might occur in up to 10% of long-haul airline travelers (12).

The risk of VTE is approximately 2- to 4-fold increased after air travel. It rises with increasing flight exposure and in certain high-risk groups.

What Factors Increase the Risk of Developing Flight-Related Venous Thromboembolism (VTE)?

The Multiple Environmental and Genetic Assessment (MEGA) study analyzed the risk factors for VTE associated with various modes of travel (13).

The risk flight-related VTE was similar to the risk associated with traveling by car, bus, or train, and was highest in the first week after traveling.

The study found that women on oral contraceptives have up to a 40 times greater chance of developing VTE on long-haul flights.

Overweight and obese passengers were also at increased risk for VTE on long-haul flights.

The risk of flight related VTE increases almost 20 times among passengers who have recently undergone surgery (14).

The risk is also increased among pregnant women and patients with cancer. A prior history of VTE is also a risk factor.

Tall individuals (> 6.2 feet or 190 cm) also appear to be at increased risk.

Having a particular mutation (known as factor V Leiden) in a gene involved in blood clotting increases the risk of VTE.

Pregnant women, women on oral contraceptives, overweight and obese passengers, tall individuals, and patients with cancer are at increased risk of flight-related VTE. Genetic factors also play a role.

Why Do Long-Haul Flights Increase the Risk of Venous Thromboembolism (VTE)?

The increased risk of VTE during air travel may be due do several factors.

Flight atmospheric pressure inside commercial aircraft is usually maintained at levels similar to that found at altitudes of 6 – 8.000 feet (1.800 – 2400 meters) above sea level. At such heights, the partial oxygen pressure of air is 20-30 percent lower than at sea level leading to a fall in the oxygen saturation of the blood during flight.

Prolonged deficiency in the amount of oxygen reaching the tissues (hypoxia) during long flights may activate coagulation pathways in blood, increasing the risk of blood clotting.

Interestingly, long-distance travel, by both air or land, is associated with a slightly increased risk of VTE (9).

Lack of movement of venous blood in the lower limbs (venous stasis) provoked be seated positions maintained in small space for long periods appears to be an important trigger for VTE. Such circumstances are commonly encountered on long-distance travel by air or land.

Dehydration is another important factor that may contribute to VTE.

The humidity onboard commercial aircraft ranges from 6-18% depending on the compartment (15). Optimal humidity varies between 40-70%. Hence, cabin air very dry.

Drinks that are known to increase urination, such as alcoholic beverages, coffee and tea, may increase the risk of dehydration.

There is a clear relationship between the length of flight and the risk for VTE.

Overall, the risk of VTE is increased twofold in long-distance flights (>8 h). The risk is 26% higher for each 2-hour increase in travel duration (16).

Long-haul flights are associated with an increased risk of VTE. The risk increases with the length of travel.

Economy Class Syndrome and Window Seating. Does it Matter Where One Sits?

Despite the term ‘economy class syndrome’ being used frequently to describe flight-related VTE, there appears to be a small difference between passengers traveling on economy and business class.

One study found that passengers who travel in a window seat are at double risk of DVT compared to passengers traveling in aisle seats (17).

Overweight subjects with a window seat seem to be at particularly high risk.

Being anxious or sleeping during the flight also appears to icreas risk.

There may be a slightly lower risk of VTE among patients flying business class compared to economy class. Passengers who travel in window seats appear to be at higher risk than passengers traveling in aisle seats.

Limited mobility increases the risk of flight related venous thromboembolism (VTE)

Are Commercial Airline Pilots and Flight Attendants at Increased Risk of Venous Thromboembolism (VTE)?

Because of the increased risk of flight-related VTE, commercial airline pilots and cabin crew may be at increased risk.

It has even be suggested that pilots may be at higher risk than cabin crew because they undertake less physical activity during flight.

In Dutch study of 2.630 airline pilots, the rate of VTE was 0.3 per 1.000 each year. This incidence rate is slightly lower than in the general population (18).

The risk did not increase with number of flight-hours per year and was not associated with the ranks of the pilots.

A review of the database of the Civil Aviation Authority for 1990–2000 shows 27 cases of VTE. The mean population at risk over the whole period was 9775, which yields an approximate incidence of 0·2 per 1000 each year which is lower than in the general population (19).

A large study from Harvard University published 2018 aimed at estimating the health consequences of flight attendant work relative to the general population (20).

The study showed that flight attendants had a higher prevalence of fatigue, depression, anxiety, sleep disorders, and all cancers. However, the risk of VTE was not increased compared to the general population.

It has not been shown that commercial airline pilots and flight attendants are at increased risk of VTE.

What General Measures May Help Prevent Flight-Related Venous Thromboembolism (VTE)?

Several underlying factors may be responsible for the increased risk of VTE during long-haul flights.

Immobility appears to be an important factor. Hypoxia and dehydration may also contribute.

Alcohol consumption may theoretically promote both immobility and dehydration.

Preventive measures are not necessary for most travelers. However, in individuals at risk on flights of six hours or more, preventive measures may be recommended.

Individuals at risk for flight-related VTE may benefit from simple measures such as frequent ambulation, calf muscle stretching, sitting in an aisle seat if possible, or the use of below-knee graduated compression stockings (21).

Avoidance of dehydration, alcohol or other sedatives is recommended. Water is preferred rather than beverages containing caffein (sucha s coffee or tea) which may promote diuresis.

Below-knee graduated compression stockings (15 to 30 mmHg pressure at the ankle) may help reduce the risk of VTE (22).

For long-distance travelers who are not at increased risk for VTE, the current guidelines suggest against the use of below-knee graduated compression stockings (20).

Individuals at risk for flight-related VTE may benefit from simple measures such as frequent ambulation, calf muscle stretching, sitting in an aisle seat if possible, or the use of below-knee graduated compression stockings. Avoidance of dehydration, alcohol or other sedatives is recommended.

Can Pharmacologic Prophylaxis Help Prevent Flight-Related Venous Thromboemboslism (VTE)?

Data are insufficient when it comes to the administration of routine pharmacologic measures.

Recently there has been a tendency in health care to administer pharmacologic VTE prevention for every patient, regardless of risk. As a result, many patients may receive unnecessary therapies that provide little benefit and could have adverse effects.

Current guidelines do not recommend the use of aspirin or anticoagulant therapy to prevent VTE in long-distance travelers (21).

For travelers who are considered to be at particularly high risk for VTE, the use of antithrombotic agents should be considered on an individual basis because the adverse effects may outweigh the benefits.

In patients who are already receiving anticoagulation (blood thinning drugs), no additional measures to prevent VTE are needed (9).

Platelet inhibitors such as aspirin have not been shown to prevent flight related VTE (8).

Some studies suggest that low molecular weight heparin (LMWH) may help prevent flight-related VTE. For example, enoxaparin at a dosage of 1 mg/kg, via subcutaneous injection, 2-4 hours before departure appears to significantly reduce the risk of VTE on long-haul flights (8).

The used of Direct Oral Anticoagulants (DOACSs) such a as dabigatran rivaroxaban, apixapan, edoxaban) for the treatment and prevention of VTE has increased in recent years.

Although these drugs appear promising, studies have not been conducted to confirm their efficacy and safety for preventing flight-related VTE. (23)

Current guidelines do not recommend the use of aspirin or anticoagulant therapy to prevent VTE in long-distance travelers. For travelers who are considered to be at particularly high risk for VTE, the use of antithrombotic agents should be considered on an individual basis because the adverse effects may outweigh the benefits.

The Bottom Line

VTE refers to a blood clot that starts in a vein. Two clinical entities are associated with VTE; deep vein thrombosis (DVT) and pulmonary embolism (PE).

The risk of VTE is approximately 2- to 4-fold increased after air travel. It rises with increasing flight exposure and in certain high-risk groups.

Long-haul flights in particular are associated with an increased risk of VTE. The risk increases with the length of travel.

Pregnant women, women on oral contraceptives, overweight and obese passengers, tall individuals, and patients with cancer are at increased risk of flight-related VTE. Genetic factors also play a role.

There may be a slightly lower risk of VTE among patients flying business class compared to economy class. Passengers who travel in window seats appear to be at higher risk than passengers traveling in aisle seats.

Commercial airline pilots and flight attendants do not appear to be at increased risk of VTE.

Individuals at risk for flight-related VTE may benefit from simple measures such as frequent ambulation, calf muscle stretching, sitting in an aisle seat if possible, or the use of below-knee graduated compression stockings.

Avoidance of dehydration, alcohol or other sedatives is recommended.

Current guidelines suggest against the use of aspirin or anticoagulant therapy to prevent VTE in long-distance travelers.

However, for travelers who are considered to be at particularly high risk for VTE, the use of antithrombotic agents should be considered on an individual basis because the adverse effects may outweigh the benefits.

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LDL-Cholesterol – The “Bad” Cholesterol Explained

Estimated reading time: 11 minutes

There are several reasons why we should be interested in the amount of cholesterol circulating in our bloodstream. However, to interpret our cholesterol numbers, we have to know certain things about cholesterol and its role in health and disease.

What Is Cholesterol?

Cholesterol is classified as a sterol (a combination of steroid and alcohol) and belongs to a group of substances called lipids.  It is a major structural component of cell membranes. Many essential hormones and vitamins are synthesized from cholesterol.

Dietary cholesterol is only found in foods of animal origin.

Although cholesterol is necessary for the human body, we don’t have to consume it. The liver can synthesize cholesterol. Therefore, it is not needed in the diet.

If our nutritional status is otherwise sufficient, we can live on a cholesterol-free diet because the body will produce the cholesterol needed.

How Is Cholesterol Transported in Blood?

Lipids are insoluble in water and can, therefore, not be transported in blood on its own.

To make lipids soluble in blood, the body straps lipids to specific proteins that function as transport vehicles.

These proteins carry different types of fats, such as cholesterol, triglycerides (TG), and phospholipids (1). These combinations of fats and protein are termed lipoproteins.

Lipoproteins

There are five major types of lipoproteins; chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) (2,3).

LDL is called low-density lipoprotein because LDL particles tend to be less dense than other cholesterol particles.

The function of LDL is to deliver cholesterol to cells.

Excess cholesterol from cells is brought back to the liver by HDL in a process known as reverse cholesterol transport.

The liver is responsible for the production and clearance of lipoproteins.

LDL vs. HDL- Cholesterol – What’s the Difference?

LDL-cholesterol (LDL-C) is often called the “bad” cholesterol, whereas HDL-cholesterol (HDL-C) is termed the “good” cholesterol.

This is because high levels of LDL-C are associated with increased risk of heart disease, whereas high HDL-C is associated with less risk.

Of course, it is the same cholesterol. The difference is the lipoproteins.

Many studies have shown a strong correlation between LDL-C and the risk of coronary heart disease (4). 

However, some studies have suggested that low LDL-C may be associated with increased mortality in older adults (5).

Much available evidence suggests that lowering blood levels of LDL-C reduces the risk of heart disease (6).

However, not all people with high levels of LDL-C develop heart disease. Furthermore, many patients who develop heart disease do not have high LDL-C.

Some studies show that the number of LDL particles (LDL-P) may be a better predictor of risk than LDL-C (7,8).

LDL particle size may also be important when assessing risk. Thus, having small LDL particles is associated with higher risk (9).

Familial Hypercholesterolemia

There are specialized receptors on cell surfaces that bind LDL-C. These are called LDL-receptors.

A lack of LDL-receptors may reduce the uptake of cholesterol by the cells, forcing it to remain in the circulation, thereby raising blood levels.

Familial hypercholesterolemia is a genetic disorder where the LDL-receptors don’t function correctly (10). Consequently, LDL cannot be removed from the blood, leading to high LDL-C levels in the blood, which may severely increase the risk of heart disease, even at a young age.

How Is LDL-Cholesterol Calculated?

Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood in the US. Canada and most European countries measure cholesterol in millimoles (mmol) per liter (L) of blood.

Although blood tests typically report LDL-C, these numbers are usually not based on measurements but a calculation using the so-called Friedewald equation (11).

Direct LDL-C measurements are available but are less often done due to higher costs.

The Friedewald equation includes total cholesterol, HDL-C, and triglycerides. This equation assumes that the ratio of triglyceride to cholesterol is constant, which is not always the case (12).

Thus, LDL-C calculations may have limitations when blood triglyceride levels are either high or low. 

 

If mg/dl is your unit, like in the US, the formula looks like this:

LDL cholesterol = [Total cholesterol] – [HDL cholesterol] – [TG]:5

 

If mmol/l is your unit like in Australia, Canada, and Europe, the formula looks like this:

LDL cholesterol = [Total cholesterol] – [HDL cholesterol] – [TG]:2.2

 

 

LDL-Cholesterol Range

It is considered essential to keep cholesterol levels, especially LDL-C, within certain limits.

If other risk factors are present, such as high blood pressure, diabetes, or smoking, keeping LDL-C low becomes even more critical. Hence, when considering the “normal” range for LDL-C, other risk factors have to be considered.

Here is how LDL-C levels are interpreted:

 

– above 190 mg/dL (4.9 mmol/L) is considered very high

– 160 – 189 mg/dL (4.1 – 4.9 mmol/L) is considered high

– 130 – 159 mg/dL (3.4 – 4.1 mmol/L) is considered borderline high

– 100 – 129 mg/dL (2.6 – 3.3 mmol/L) is considered near ideal

– below 100 mg/dL (below 2.6 mmol/L) is considered ideal for people at risk of heart disease

– below 70 mg/dL (below 1.8 mmol/L) is considered ideal for people at very high risk of heart disease

How To Lower LDL-Cholesterol

For many individuals, reducing LDL-C may lower the risk of heart disease.

If LDL-C is high, most doctors will probably suggest lifestyle changes.

Quitting smoking will be helpful, and so may eating whole grain, oatmeal, olive oil, beans, fruit, and vegetables.

Most doctors will recommend eating less saturated fat, found primarily in meat and dairy products.

Trans fats should be avoided. These fats are found in fried foods and many commercial products, such as cookies, crackers, and snack cakes.

However, keep in mind that food products labeled “trans-fat-free” may still contain some trans fat. In the US, if a food is labeled “trans-fat-free” if it contains less than 0.5 grams of trans fat in a serving.

Soluble fiber may help lower LDL-C. It is found in oats and oat bran, fruits, beans, lentils, and vegetables.

Some studies show that low-carbohydrate diets may positively affect LDL particle size and number (13).

Weight loss in overweight or obese people is usually recommended.

If lifestyle changes don’t help, your doctor may suggest medications that lower cholesterol. So-called statins are the most commonly used drugs for lowering cholesterol.

Studies have shown that statins improve prognosis among patients with established cardiovascular disease.

Their role for treatment of raised LDL-C in healthy people (primary prevention) is less clear (14). 

The decision to give statins in primary prevention is usually based on other risk factors as well as the LDL-C value itself (15).

 

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Dizziness – 20 Questions and Answers About Dizziness, Vertigo, and Presyncope

Estimated reading time: 18 minutes

Dizziness is a term that is used to describe a feeling of wooziness, lightheadedness or being off balance. Sometimes it is also used to describe a spinning sensation or a sensation of movement although in such cases the term vertigo will fit better.

In Alfred Hitchcock’s masterpiece, Vertigo, James Stewart plays ex-cop Scottie, invalided out of the police due to vertigo brought on by a traumatic and shaming calamity during a rooftop chase.

Dizziness is a nonspecific symptom that often means different things to different people. As the symptoms are usually quite vague and can be caused by a wide range of disorders, the underlying cause may often be difficult to define.

Dizziness accounts for an estimated 5 percent of primary care clinic visits. A final diagnosis is not obtained in about 20 percent of cases (1).

Usually, dizziness alone is not a sign of a severe underlying disease, especially if it passes after a few minutes.

Dizziness can occur in people of any age but is more common among older adults. It commonly leads to falls and sometimes injuries among the elderly. Often, the fear of dizziness may cause older adults to limit their activities.

1. How Does the Vestibular System Work?

In the majority of cases, the cause of dizziness may be traced to the vestibular system.

The vestibular system is a sensory system responsible for providing the brain with information about motion, head position, and spatial orientation.

The two main components of the vestibular system are the peripheral vestibular component and the central vestibular component.

The vestibular system is a sensory system responsible for providing the brain with information about motion, head position, and spatial orientation. The main components of the vestibular system are found in the inner ear.

The peripheral portion of the vestibular system is a part of the inner ear and is composed of three semicircular canals, two otolithic organs (the utricle and the saccule), and the vestibulocochlear nerve. 

The purpose of the semicircular canals is to detect rotational movements of the head. For example, the semicircular canals are activated when we turn our head left and right or when we tilt our head up and down (2).

Rotational head movements cause the fluid in the semicircular canals to move. The fluid movement causes hair cells in the semicircular canals to bend leading to stimulation of the vestibulocochlear nerve.

The purpose of the vestibular nerve is to transmit balance-related information from the semicircular canals and the otolithic organs to the central portion of the vestibular system which is located in the brainstem, cerebellum, and other parts of the brain (2).

Hence, the peripheral vestibular system acts as a miniaturized accelerometer and inertial guidance device, continually reporting information about the motions and position of the head and body to the brain (3).

The central portion of the vestibular system is composed of the vestibular nuclei in the brain and its ascending and descending tracts.

The role of the vestibular nuclei is to process the balance-related information from the peripheral vestibular system along with visual information from the eyes and somatosensory information from the muscles.

Once the brain has made sense of all of the incoming information, it transmits outgoing signals to control the movement of the eyes and muscles of the body.

The eyes are primarily stabilized through the vestibulo-ocular reflex (VOR), and the body is stabilized mainly through the vestibulospinal reflex (VSR). 

2. What Are the Most Common Causes of Dizziness?

A few disorders are lumped under the term dizziness. The most common are vertigo, nonspecific dizziness, disequilibrium, and presyncope (1,4). Fitting the patient onto one of these categories is practical.

It has been estimated that approximately 40% of dizziness is caused by a dysfunction of the balance organs of the inner ear (4). This is called peripheral vestibular dysfunction.

The three most frequent forms of peripheral vestibular disorders are – in the order of their frequency – benign paroxysmal positioning vertigo (BPPV), Menière’s disease, and vestibular neuritis (5).

Approximately 10 percent of patients with dizziness have a central brainstem vestibular lesion; 15% have a psychiatric disorder; and 25 percent have other problems, such as presyncope and disequilibrium (4).

Elderly patients are more likely than younger people to have a central brainstem vestibular lesion as a cause of their dizziness. This is most often due to stroke.

3. How Is the Cause of Dizziness Identified?

The patient’s description is critical for finding the cause of dizziness.

The history taking should focus on the nature of the symptoms, the duration, and triggering or alleviating factors.

It may be helpful to ask the patient to use other words than “dizzy.” The rationale for this is that patients may use “dizzy” nonspecifically to describe vertigo, unsteadiness, generalized weakness, syncope, presyncope, or falling (6).

A simple way of distinguishing between ear-related dizziness and dizziness due to other causes is to determine whether it occurs only when the patient is upright or also when he/she is lying down. Dizziness that occurs only in the upright position is unlikely to be related to the ear.

The patient should be asked if there is any hearing loss, tinnitus or drainage from the ear. 

The general examination of the patient includes an assessment of vital signs, supine and standing blood pressure measurements, and evaluation of the cardiovascular and neurologic systems. 

The ears should be inspected for signs of infection or inflammation of the external or middle ear. 

It is essential to distinguish vertigo, which is a subtype of dizziness, from other types of dizziness.

Testing for nystagmus is of key importance. The presence of nystagmus suggests that dizziness is vertigo (4).

4. What Is Vertigo?

Like dizziness, vertigo is a symptom, not a diagnosis. Vertigo is only one type of dizziness.

Vertigo is an illusion of movement most often caused by an asymmetric input to the vestibular system.

Most people have experienced vertigo as the spinning sensation experienced after turning around rapidly several times.

Although the most common perception is a spinning sensation, terms like “whirling,” “tilting” or “moving” are often used (4).

It is important to distinguish vertigo from other types of dizziness. Although the spinning component is characteristic of vertigo, many patients have difficulty in putting their experience into words.

The time course and knowledge of provoking and aggravating factors may help determine the underlying cause. 

The presence of nystagmus suggests that dizziness is vertigo.

The Time Course of Vertigo

Vertigo is never continuous for more than a few weeks (4). 

However, patients may have repeated spontaneous attacks. These may be caused by Meniere disease, vestibular migraine or benign paroxysmal positional vertigo.

Episodic vertigo that lasts for days with nausea and no other ear or central nervous symptoms is usually due to vestibular neuritis (6). This type of vertigo may also be caused by multiple sclerosis or stroke.

Vestibular neuritis often occurs following a viral illness.

Episodic vertigo that lasts for seconds and is associated with head or body position changes is probably due to benign paroxysmal positional vertigo (BPPV) (7).

Vertigo that lasts for hours may be caused by Meniere disease

Vertigo of sudden onset that lasts for minutes may be due to migraine or cerebrovascular disease (6).

Constant dizziness lasting months may often be psychogenic.

Provoking and Aggravating Factors

When distinguishing vertigo from other types of dizziness, it is practical to remember that all vertigo is made worse by moving the head.

If the head motion does not make symptoms worse, the patient probably does not have vertigo but suffers from another type of dizziness.

5. What Is Nystagmus?

Nystagmus refers to rapid involuntary movements that may cause one or both eyes to move from side to side, up and down or around in circles.

The presence of nystagmus is tested by having the patient follow the examiner’s finger up and down and left an right.

Lateral gaze is tested with the examiner’s finger placed >60 degrees from midline.

The presence of nystagmus suggests that dizziness is vertigo. However, there are many types of nystagmus.

In a patient with acute vertigo, nystagmus may be found with the patient looking straight ahead.

The absence of nystagmus suggests that vertigo is unlikely. Hence, other types of dizziness should be considered.

Some types of nystagmus are only seen after a provocative maneuver like the Dix-Hallpike maneuver.

6. What Is the Dix-Hallpike Test?

In 1952, Dix and Hallpike performed the provocative positional testing named in their honor.

The Dix-Hallpike maneuver is used to provoke vertigo and elicit nystagmus in patients with dizziness that is not present at rest. It is commonly used to diagnose benign paroxysmal positional vertigo (BPPV) (8).

The patient is positioned sitting upright in bed, such that when supine the head will hang over the edge. Next, the head is turned 45°to one side. The patient is then placed supine rapidly so that the head hangs over the edge of the bed. The presence of nystagmus is observed for 30 seconds.

The Dix-Hallpike maneuver is used to provoke vertigo and elicit nystagmus in patients with dizziness that is not present at rest. It is commonly used to diagnose benign paroxysmal positional vertigo (BPPV)

The test is then repeated with the head turned in the other direction.

If the Dix Hallpike test is positive, the patient will experience vertigo and nystagmus will be observed. Position the patient sitting upright on the bed, such that when supine their head will hang over the edge.

7. What Is Benign Paroxysmal Positional Vertigo (BPPV)?

Benign paroxysmal positional vertigo (BPPV) is probably the most common cause of vertigo in the United States. It has been estimated that at least 20% of patients who present to the physician with vertigo have BPPV (7).

BPPV is defined as an abnormal sensation of motion that is elicited by certain provocative positions. These provocative positions usually trigger nystagmus.

Apart from dizziness and vertigo the signs and symptoms of BPPV may include a loss of balance, nausea and vomiting.

The signs and symptoms of BPPV can come and go, with symptoms commonly lasting less than one minute. Episodes of benign paroxysmal positional vertigo can disappear for some time and then recur (9).

Activities that bring about the signs and symptoms of BPPV are almost always brought on by a change in the position of the head.

The Dix-Hallpike maneuver is the standard clinical test for BPPV.

The Cause of BPPV

The otolith organs, the utricle and saccule, monitor movements of the head and the head’s position related to gravity.

The otolith organs contain calcium crystals that make us sensitive to gravity. The crystals give the otolith organs their name (otolith is Greek for “ear stones”) (10). These crystals can become dislodged.

BPPV occurs when the tiny calcium crystals are displaced from the otolith organs the utricle and saccul) of the inner ear and fall down into one of the semicircular canals, disrupting the flow of the fluid in that canal.

BPPV occurs when the tiny calcium crystals are displaced from the otolith organs of the inner ear and fall down into one of the semicircular canals, disrupting the flow of the fluid in that canal.

The presence of crystals in the semicircular canals causes them to become sensitive to head position changes it would normally not respond. This leads to dizziness and vertigo.

People with BPPV often suffer from short episodes of severe vertigo with change in head or body position, such as turning over in bed or getting up and out of bed, tilting their head back in the shower to wash their hair, or turning their head from side to side while driving. The onset of vertigo can be very sudden and very frightening (11).

The Treatment of BPPV

Canalith repositioning is the preferred treatment for BPPV.

The reposition maneuvers incorporate a specific series of head and body movements designed to move the displaced calcium crystals out of the affected semicircular canal.

This series of movements is typically completed in a short period of time, but repetition may sometimes be required.

There are several types of repositioning maneuvers, including the Epley maneuver, the Semont, and the Appiani, which are specific to the semicircular canal that is involved (13).

Other treatment options include watchful waiting, vestibulo-suppressant medication, vestibular rehabilitation, and surgery.

8. What Is Vestibular Neuritis?

Vestibular neuritis, also known as vestibular neuronitis and labyrinthitis, is believed to be a viral or postviral inflammatory disorder, affecting the vestibular portion of the vestibulocochlear nerve (12).

Vestibular neuritis is characterized by the rapid onset of severe, persistent vertigo, nausea, vomiting, and gait instability (13).

Physical examination usually shows gait instability and the presence of nystagmus.

When this syndrome is combined with unilateral hearing loss, it is called labyrinthitis.

Generally, the most severe symptoms only last a couple of days, but while present, make it extremely difficult to perform routine activities of daily living (14).

Most patients make a slow, but full recovery over the next several weeks (approximately three weeks). However, some patients can experience balance and dizziness problems that can last for several months.

It is important to rule out other illnesses, such as stroke, before a diagnosis of vestibular neuritis is made.

Medications may be prescribed to control nausea and to suppress dizziness during the acute phase. Examples include Benadryl (diphenhydramine), Antivert (meclizine), Phenergen (promethazine hydro¬chloride), Ativan (lorazepam), and Valium (diazepam). Other medications that may be prescribed are steroids (e.g., prednisone), an antiviral drug (e.g., Acyclovir), or antibiotics (e.g., amoxicillin) if a middle ear infection is present (15).

9. What Is Meniere Disease?

Meniere’s disease is a disorder of the inner ear that causes vertigo and hearing loss.

It is a peripheral vestibular disorder attributed to excess endolymphatic fluid pressure, which causes episodic inner ear dysfunction (12).

Meniere’s disease can occur at any age, but it usually starts between young and middle-aged adulthood. It’s considered a chronic condition, but various treatments can help relieve symptoms and minimize its long-term impact (13).

The disease is characterized by spontaneous episodic vertigo lasting for minutes to hours, usually associated with unilateral tinnitus, hearing loss, and ear fullness.

10. What Is Vestibular Migraine?

Migraine is increasingly recognized as a cause of recurrent vertigo. However, the mechanism whereby migraine causes vertigo is not understood, and the diagnosis remains somewhat controversial (12).

Vestibular migraine can cause vertigo, dizziness, nausea and vomiting the with or without the headache that is typical of most migraines (13).

Episodes of migraine-related dizziness generally occur spontaneously but, similar to migraine headache, can be triggered by certain foods, certain sensory stimuli, and certain situations (14).

Treatment for vestibular migraine is similar to that for other migraines, and may include medicine to stop or prevent an episode.

11. Can Vertigo Be Caused by a Stroke?

Yes, vertigo can be caused by stroke.

Cerebellar or brain stem hemorrhage or an ischemic stroke may cause intense vertigo accompanied by nausea and vomiting. This may be clinically indistinguishable from vestibular neuritis.

Computed tomography (CT) of the brain or MRI Magnetic resonance imaging) are necessary for diagnosis.

12. What Is Wallenberg Syndrome (PICA syndrome)?

Wallenberg syndrome, or lateral medullary infarction, is a specific type of stroke associated with the acute onset of vertigo and disequilibrium.

It is caused by a lateral medullary infarction, which results from occlusion of either the posterior inferior cerebellar artery(PICA) or branches of the vertebral artery. For this reason, it is also referred to as lateral medulla syndrome or PICA syndrome.

Vertigo is often the most prominent symptom. However, neurological examination usually uncovers other neurologic deficits such as abnormal eye movements, an ipsilateral Horner syndrome, ipsilateral limb ataxia, and a dissociated sensory loss (loss of pain and temperature sensation on the ipsilateral face and contralateral trunk with preserved vibration and position sense) (12).

Hoarseness and dysphagia are often present.

Patients usually recover their equilibrium after several months.

13. Can Vertigo Be Caused by Multiple Sclerosis?

Yes, multiple sclerosis (MS) may cause vertigo. In fact, vertigo has been estimated to occur in 20 percent of multiple MS patients (12).

Vertigo and dizziness in multiple sclerosis is usually caused by a growth of an existing lesion or the appearance of a new lesion on the brain stem or cerebellum, the area in the brain that controls balance (15).

However, one study noted that among 25 patients with MS complaining of vertigo, BPPV, not MS, was the underlying cause in more than half of patients (16).

14. What Is Nonspecific Dizziness?

Sometimes it is difficult for patients to describe their dizziness. They may just claim they feel dizzy. Words like lightheadedness and giddiness also fall under the category of nonspecific dizziness.

Psychiatric disorders may be the primary cause of dizziness. Sometimes dizziness is associated with depression, anxiety and panic disorder (17).

Nonspecific dizziness may be related to hyperventilation (4).

A variety of medicatoins may cause dizziness. Sometimes, abrupt drug withdrawal may cause dizziness (18).

15. What Is Disequilibrium?

Disequilibrium is a sense of imbalance that occurs primarily when walking.

Chronic or disequilibrium can cause significant impairment of physical and social functioning, particularly in the elderly (25).

One large study study estimated that approximately one in five elderly persons (above age 65) experiences annual problems with dizziness or balance (19).

The authors of the paper concluded that given the significant prevalence and negative effect of balance problems on daily activities in the elderly, balance disorders merit special attention, particularly in the face of an aging population.

Although often a part of normal aging, disequilibrium may also result from many disorders of the central nervous system such as cerebellar disorders and Parkinson’s disease.

Balance training and exercises are helpful to prevent and treat disequilibrium. Such therapy can help compensate for imbalance and maintain physical activity.

Canes may be used to reduce the risk of falls

16. What Is Presyncope?

Presyncope is the sensation that one is about to pass out. It is often described as a severe lightheaded feeling, often associated with unsteadiness or falling.

The patient often describes presyncope as by the patient as “nearly blacking out” or “nearly fainting.”

Patients may also report lightheadedness, a feeling of warmth, diaphoresis, nausea, and visual blurring occasionally proceeding to blindness. An observation of pallor by onlookers usually indicates presyncope (12) .

Presyncope usually occurs when the patient is standing or seated upright and not when supine. If presyncope occurs in the supine position, cardiac arrhythmia should be suspected (20).

Most commonly, presyncope arises because the cerebral cortex is temporarily not receiving adequate oxygen, usually because of diminished blood flow (21).

Indeed, most of us have experienced transient presyncope after rapidly standing from the lying or sitting position.

Common causes in the elderly are orthostatic hypotension, vasovagal episodes, carotid sinus syndrome (CSS), medications, anemia, viral infections, and cardiac arrhythmias.

17. What Is Orthostatic Hypotension?

Orthostatic hypotension, also called postural hypotension, is a term used to describe a low blood pressure that occurs when we stand up from a sitting or lying position.

The classical definition of orthostatic hypotension is a reduction of at least 20 mm Hg in systolic or of at least 10 mm Hg in diastolic blood pressure, measured 3 minutes after changing from a lying to standing position (21). 

Orthostatic hypotension is a common cause of dizziness and lightheadedness in the upright position. It may even cause presyncope and fainting.

Orthostatic hypotension is more common in older people.

Hypovolemia (a drop in the volume of blood) and dehydration (low fluid volume in the body) both increase the risk of orthostatic hypotension.

Hypovolemia and dehydration may be caused by bleeding, elevated blood sugar, diarrhea, vomiting, and medications like thiazide diuretics (HCTZ) and loop diuretics (furosemide, bumetanide) (22).

The risk of hypovolemia and dehydration increases in hot weather.

Patients with Parkinson’s disease often suffer from orthostatic hypotension.

Medications that are used to treat elevated blood pressure, such as beta blockers, calcium channel blockers, ACE inhibitors, nitrates, and angiotensin II blockers can induce orthostatic hypotension

Some medication for anxiety, depression, erectile dysfunction, and Parkinson’s disease may increase the risk of orthostatic hypotension.

18. What Is a Vasovagal Episode (Vasovagal Attack)?

A common cause of presyncope is an exaggerated activation of the parasympathetic autonomic nervous system leading to a bradycardia (slow heart beat) and vasodilation (i.e., vasovagal presyncope and syncope).

The increased parasympathetic activity is mediated through the vagal nerve; hence the term vasovagal attack.

Although a common cause of presyncope it is also a frequent cause of syncope or fainting (vasovagal syncope).

The increased vasovagal response is commonly induced by abdominal pain and cramping, defecation, micturition, cough, sexual activity, the sight of blood, or fear.

Intravascular volume depletion or dehydration will predispose patients to vasovagal episodes.

19. Can Cardiac Arrhythmia Cause Dizziness and Presyncope?

Cardiac arrhythmia is a relatively uncommon cause of fainting and presyncope.

Both bradycardia (slow heartbeat) and tachycardia (fast heartbeat) may induce a transient drop of blood pressure followed by reduction of cerebral blood flow, which evokes faintness and presyncope.

Since several severe types of arrhythmias may induce sudden death, it is important to recognize faintness and presyncope as a warning sign for further potentially lethal arrhythmic events in selected patients (23).

Holter ECG and event recorders are widely used for detection of arrhythmic events related with faintness/presyncope.

Symptomatic bradycardia is the most common indication for pacemaker implantation. Such bradycardia is defined as a documented slow heart beat that is directly responsible for the development of t of frank syncope or near syncope, transient dizziness or light-headedness, and confusional states resulting from cerebral hypoperfusion and attributable to low heart rates (24).

Current pacemaker devices also treat tachyarrhythmias and are often combined with implantable defibrillators.

20. Can Low Blood Sugar Cause Dizziness and Presyncope?

Hypoglycemia (low blood sugar) is the most common metabolic cause of presyncope.

Hypoglycemia is often related to the treatment of diabetes. However, a variety of conditions can cause low blood sugar in people without diabetes.

Other symptoms associated with hypoglycemia may be fatigue, pale skin, shakiness, anxiety, sweating, hunger, irritability, and a tingling sensation around the mouth (25).

Hypoglycemia usually occurs during prolonged fasting.

Sometimes hypoglycemia occurs after meals because the body produces more insulin than is needed. This is called called reactive or postprandial hypoglycemia.



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