The 28th Nordic-Baltic Congress of Cardiology will be held in Reykjavik, Iceland, June 8-10, 2023. This is a perfect time to visit Iceland. The subtitle of the meeting is THE FUTURE OF CARDIOLOGY.
The conference will be held in Harpa which is one of Reykjavik’s greatest and most famous landmarks.
There is a long history behind the Nordic-Baltic Congress of Cardiology. Traditionally, the conference is held every two years, usually at the beginning of June. It was last hosted in Helsinki, Finland, in the early summer of 2019. Due to the Covid-19 pandemic, four years have now passed since the latest conference.
This is the fourth time the congress has been held here in Reykjavik. It was also hosted here in 1989, 1999, and 2009 and as a matter of fact, I’ve had the pleasure of actively participating in all these meetings. I presented my first scientific abstract at an international meeting here in 1989.
This time I will chair a session called PREVENTION ACROSS THE METABOLIC SPECTRUM. Three renowned speakers will give talks at the session; Prof. Pam R. Taub from San Diego, USA, Prof. Kosh Ray from London, UK, and Prof Lars Ryden from Stockholm, Sweden.
I will also participate in another session aimed at young cardiologists called WHY THE FUTURE IS PREVENTION – EVERYTHING A FELLOW NEEDS TO KNOW ABOUT LIPIDS.
I believe the conference will provide a great overview of many of the most important areas of cardiology.
Several sessions will be aimed at young cardiologists. There will be a nursing program as well.
Among subjects that will be addressed at the conference are:
NUTRITION, OBESITY, AND LIPIDOLOGY
SECONDARY PREVENTION IN CORONARY ARTERY DISEASE
ISCHEMIC HEART DISEASE, INTERVENTIONS AND GUIDELINES IN PRACTICE
MANAGEMENT OF ATRIAL FIBRILLATION
THE ROLE OF GENETICS IN CARDIOVASCULAR DISEASE MANAGEMENT
ANTIPLATELET THERAPY AND BLEEDING RISK IN CARDIAC SURGERY PATIENTS
CARDIOVASCULAR IMAGING
HYPERTROPHIC CARDIOMYOPATHY
ADULTS WITH CONGENITAL HEART DISEASE
PERCUTANEOUS VALVE INTERVENTIONS
THE MANY FACES OF HEART FAILURE
CARDIOVASCULAR DISEASE IN THE ELDERLY
CANCER TREATMENT AND CARDIO -TOXICITY
THE AUTONOMIC NERVOUS SYSTEM
THE HEART AND SLEEP
ARRHYTHMIAS AND RISK ASSESSMENT
CARDIOVASCULAR PREVENTION AND EPIDEMIOLOGY
People visiting Iceland, whether as tourists or on business, usually agree that visiting this adventure island is an amazing experience. There are many things to see and experience, both within the capital area and in the countryside.
Statin drugs play an important role in the treatment of cardiovascular disease and have been shown to improve the prognosis of patients with established atherosclerotic heart disease.
Statins, however, are not without side effects, and 7 to 29% of patients report adverse musculoskeletal effects that limit their ability to use them as recommended by clinical guidelines (1). There are few studies on alternative treatments for patients who have to stop taking statins due to side effects.
Bempedoic acid is an adenosine triphosphate (ATP) citrate lyase inhibitor that works earlier in the cholesterol synthesis pathway than statins. It catalyzes the conversion of citrate to acetyl-CoA, the basic substance needed for cholesterol synthesis (2).
Hence, similar to statins, bempedoic acid reduces the production of cholesterol by the liver. In response, liver cells produce more LDL receptors, and the uptake of cholesterol into liver cells increases. Consequently, blood levels of LDL cholesterol levels are lowered.
Bempedoic acid is a prodrug that is activated in the liver and not in skeletal muscle, which may reduce the likelihood of muscle-related side effects.
The recently published CLEAR Outcomes trial (presented in New Orleans yesterday at the 2023 Annual Sccientific Meeting of the American College of Cardiology) showed that bempedoic acid improves long-term cardiovascular outcomes compared with placebo among patients with either established atherosclerotic cardiovascular disease (ASCVD) or who have a high risk for it, and with intolerance to statin therapy (3).
Bempedoic Acid and the CLEAR Outcomes Trial
The goal of the trial was to compare the safety and efficacy of bempedoic acid compared with placebo among patients with or at high risk for ASCVD and were intolerant of statin therapy.
Patients 18 to 85 years of age were eligible if they met either of two criteria for increased cardiovascular risk — a previous cardiovascular event (secondary-prevention patients) or clinical features that placed them at high risk for a cardiovascular event (primary-prevention patients).
Eligible patients had to report being unable or unwilling to receive statins owing to an adverse effect that had started or increased during statin therapy and resolved or improved after statin therapy was discontinued (“statin-intolerant” patients).
Fasting blood low-density lipoprotein cholesterol (LDL-C) had to be ≥100 mg/dl (2.6 mmol/L) at screening. Other lipid-lowering therapies were permitted.
Patients were randomized in a 1:1 fashion to either bempedoic acid 180 mg (n = 6,992) or placebo once (n = 6,978) daily.
Total number of enrolled patients: 13,970
Duration of follow-up: 40.6 months (median)
Mean patient age: 65.5 years
Percentage female: 48%
Percentage with diabetes: 46%
The primary outcome, four-component major adverse cardiovascular events (MACE: nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or CV death) for bempedoic acid compared with placebo, was: 11.7% vs. 13.3%, hazard ratio 0.87, 95% confidence interval 0.79-0.96 (p = 0.004).
Bempedoic acid lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, myocardial infarction (MI), stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%. The drug was also well-tolerated
The absolute risk reduction was 1.6%. The calculated number needed to treat for 40 months to prevent one event was 63. This implies that 63 patients have to be treated for three years and four months to prevent one event. Impressive or not. I’m not really sure.
According to an editorial published in the NEJM, bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk (4).
However, there was no significant difference in all-cause mortality between bempedoic acid compared with placebo (6.2 vs. 6.0%). On this observation the authors of the paper have pointed out that many individual trials of statins have also not shown an effect of on mortality and that it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear (5).
Still, in my opinion, the lack of effect on mortality remains a matter of concern.
A hugely important question for the clinical cardiologist is whether Covid-19 vaccinations reduce the risk of cardiovascular complications following Covid-19 infections.
It is well-documented that being infected with SARS-CoV-2 increases the risk of short-and long-term cardiovascular complications, many of which may be severe. Therefore, practicing clinicians and patients will embrace every tool that can be used to bring down this exposedness.
One of the things we learned some time ago is that, unfortunately, the first and second doses of COVID-19 vaccination may be associated with an increased risk of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the pericardium,)(1, 2). This, of course, has given rise to considerable scientific and public interest and has been highlighted by anti-vaccination movements.
However, evidence shows that the risk of myocarditis is substantially higher after Covid-19 infection in unvaccinated individuals than the increase in risk observed following vaccination. Furthermore, vaccine-associated myocarditis is largely restricted to men younger than 40 years with (3). Obviously, this still remains a matter of great concern.
Now, recently published data from the US shows that vaccination against COVID-19 is associated with fewer major adverse cardiovascular events (MACE) among people suffering from-Covid 19 when compared to unvaccinated patients. The researchers used the National COVID Cohort Collaborative (N3C) database, the largest national comprehensive database on COVID-19. The study results were published online in the Journal of the American College of Cardiology on February 20 (4). The results are presented in a letter and therefore I’m assuming this is not a peer reviewed paper.
The patients studied were between ages 18-90 and were initially infected with SARS-CoV-2 between March 1, 2020, and February 1, 2022. The follow-up time was 180 days from the start of the infection. The following vaccines were used: mRNA vaccines by Pfizer-BioNTech and Moderna, as well as vector vaccines by Johnson and Johnson.
The study addressed 1,934,294 patients, the mean age was 45.2 years, and 55.9% were women. A total of 195,136 patients were fully vaccinated, which interestingly is only 10.1 percent. The number of partially vaccinated was 22,707 (1.2%), and 1,716,451 (88.7%) were not vaccinated.
The median time to MACE after infection was 17 days, and the median time from the last vaccination to MACE was 212 days.
Figure A above is a plot of the probability that patients do not develop MACE versus time since their initial SARS-CoV2 infection, stratified by vaccination status. Figure B above is a depiction of hazard ratio associated with MACE according to each examined factor. Mount Sinai press release New York, NY (February 20, 2023). Link to https://www.mountsinai.org/about/newsroom/2023/covid-vaccination-linked-to-fewer-cardiac-events
Overall, MACE was observed among 13,948 patients (0.72%): 12,733 cases occurred among non-vaccinated patients (0.74%), 160 in partially vaccinated patients (0.70%), and 1,055 in fully vaccinated patients (0.54%). In total, 3175 patients died after MACE.
Medscape Medical News reports that patients who were fully vaccinated had a 41% lower risk of experiencing a cardiac event compared to those who were not vaccinated. Partially vaccinated people had a 24% lower risk (5).
However, using the relative difference may be misleading. According to my own look at the numbers and assuming there is a protective effect of the vaccination, the number needed to treat will be 500. In other words, 500 patients need to be vaccinated to prevent one cardiac event from Cocid-19.
Taking into consideration that Covid-19 is a very common and widespread disease, the effect may indeed be huge. With an NNT of 500, vaccinating on million people may prevent 2.000 cardiac complications.
The results suggest that the difference between vaccinated and non-vaccinated people may be most pronounced in patients with a previous history of cardiovascular disease, patients with type 2 diabetes, lipid problems, liver disease, and obesity. Furthermore, the proposed benefits of vaccinations seem to increase with advancing age.
Of course, this is not a randomized trial, and we must remember that an association does not prove causality. However, the size of the study certainly suggests that Covid-19 vaccinations indeed do appear to provide protection against the cardiac complications of Covid-19. This may be particularly true for some subgroups of patients who are at higher risk.
Although we have recently seen tremendous progress in the development of medical treatments for metabolic disorders and obesity, I still believe that nutritional and lifestyle measures are key to long-term success. As such, intermittent fasting is an exciting approach that, if used sensibly, is likely to reduce body weight and improve metabolic health. Animal studies have even suggested that it may promote healthy aging and increase longevity.
Our human ancestors had different food habits than we do. They did not routinely eat two to three regularly spaced, large meals every day. Indeed, food was often scarce, and there may have been long periods between meals. Furthermore, through the ages, fasting has been practiced in many communities for cultural and religious purposes.
As a result, the human body has developed many adaptive mechanisms that allow survival when food is not available. Hence, intermittent fasting is usually well tolerated and appears to be harmless for healthy, normal-weight, and obese adults. Nevertheless, it is crucial to eat a balanced diet and conform to healthy eating rules during intermittent fasting.
Intermittent fasting allows drinking unsweetened beverages such as water, coffee, and tea during the fasting period.
This article aims to answer several essential questions about intermittent fasting and the current scientific evidence supporting its benefits.
What Is Intermittent Fasting?
Intermittent fasting involves alternating cycles of fasting and eating. This may be done in many different ways.
Examples of methods used include alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and the 16:8 diet.
Alternate-day fasting implies fasting every other day (1).
Modified alternate-day fasting allows for some caloric intake on the “fasting day”, though severely restricted (~75% caloric restriction).
The 5:2 diet (also termed the “Fast” diet) prescribes two days of severe caloric restriction per week and a regular diet five days a week (2). The diet allows for the consumption of about 400–600 kcal on the “fasting” days.
Overeating on the “feed day” due to increased hunger following the “fast day” often becomes a concern with intermittent fasting. However, studies have concluded that even after fasting every other day, participants report no compensatory eating and high satiety (3).
Time-Restricted Eating
Time-restricted eating focuses on the timing of eating. It implies that eating is restricted to specific hours of the day (4).
Three variants of time-restricted eating are most common: 16:8, 18:6, and 20:4.
The 16:8 method has become quite popular. It consists of a 16-hour fast and then an 8-hour nutritional window where food is consumed. This can, for instance, be achieved by skipping breakfast and not eating after dinner.
Human studies have suggested that time-restricted feeding promotes weight loss (5,6). Some of these studies also showed beneficial effects on fasting blood sugar (fasting glucose) as well as LDL and HDL cholesterol.
Some experts have been skeptical about time-restricted eating because it often involves skipping breakfast (7). However, whether skipping breakfast is bad or not is still a matter of debate (8).
Are the Effects of Intermittent Fasting due to Calorie Restriction?
Calorie restriction means reducing the average daily caloric intake below what is habitual.
Studies have shown that calorie restriction can significantly reduce body weight (9). Clinical trials also indicate that calorie restriction may have a numerous beneficial effects among overweight adults in addition to weight loss. However, over the past several decades, obesity intervention trials have revealed that the vast majority of individuals experience difficulties sustaining daily calorie restriction for extended periods.
There are many similarities between calorie restriction and intermittent fasting. During intermittent fasting, a person does not eat or severely limits food intake during certain periods. This often leads to fewer calories consumed. However, it is believed that the benefits of intermittent fasting are not due to calorie restriction alone (1).
The Metabolic Effects of Intermittent Fasting
Glucose, fatty acids, and ketone bodies are the primary fuel for most cells and organs in the body.
After meals, glucose is used for energy, and fat is stored as triglycerides. During periods of fasting, triglycerides are broken down to make fatty acids available.
During intermittent fasting, the body’s cells will periodically not have access to glucose. Instead, they will use free fatty acids and ketone bodies as their primary fuel.
This is called intermittent metabolic switching or glucose-ketone (G-to-K) switchover (10).
The body can store excess glucose in the form of glycogen. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle (11).
When the body’s glycogen stores become depleted, as happens during fasting, the body starts to break down fat. The breakdown of fats increases the availability of fatty acids, which most cells can use for energy.
The onset of the metabolic switch occurs when liver glycogen stores are depleted, which is typically 12 hours after the fasting is initiated.
Indeed, the switching from the use of glucose to fatty acids and ketone bodies may explain many of the health benefits of intermittent fasting.
After nearly a century of research, it has been scientifically proven that intermittent fasting promotes healthy aging in animal research models.
The Role of Ketone Bodies
Ketone bodies are produced by the liver and used as an energy source by many cells and organs. Research indicates that the heart, kidneys, and brain prefer ketone bodies rather than glucose as their fuel resource.
When glucose is unavailable, as during fasting, the liver increases the production of ketone bodies.
Ketone levels may build up in the blood during fasting, resulting in a condition known as ketosis. Ketosis may also be caused by restricting carbohydrate consumption.
Excess ketones are excreted in urine and exhaled from the lungs.
Ketone bodies are not only used as a fuel resource. They are also potent signaling molecules that can have numerous beneficial effects on cells and organs (1).
Ketone bodies regulate the activity of many chemical substances that influence health and aging (12).
Intermittent Fasting, Physical Training, and Fitness
Both physical training and fasting have beneficial effects on health.
Aerobic exercise training and fasting increase the breakdown of fat (13). Thus, body composition is improved and lean body mass is reduced.
It has been shown that mice on intermittent fasting have better running endurance than mice that have unlimited access to food (1).
A human study showed that young men who fasted daily for 16 hours lost fat during resistance training. At the same time, muscle mass was maintained (14).
However, a recent summary of the current scientific evidence indicates that our understanding of the effects of fasting on physical performance is not complete. Although some studies are clearly positive, others have reported decreased performances, while others showed no effect. In fact, endurance athletes are often advised to avoid high-intensity training while fasting (13).
Intermittent Fasting For Weight Loss
Obesity and being overweight are strong predisposing factors for developing diabetes, heart disease, and many cancer types.
The first clinical study of fasting for the treatment of obesity was performed in 1915. The study showed that short periods of four to six days of fasting reduced body weight (14).
Many studies in rodent models of obesity have shown beneficial effects of intermittent fasting (15). Studies also show that intermittent fasting results in weight loss in humans (16,17, 18, 19, 20). Weight loss is usually rapid in the beginning, mostly due to the loss of sodium and water (21). A randomized human study showed that the 5:2 diet-induced weight loss (22).
In summary, there is abundant scientific evidence showing that intermittent fasting promotes weight loss in obese individuals. However, the longer-term benefits or harms of intermittent fasting amongst overweight or obese people are unknown (23).
Intermittent Fasting and Diabetes
Patients with diabetes mellitus, both types 1 and 2, comprise about 10% of the population in the United States (24).
Insulin resistance is a key feature of type-2 diabetes. Many studies have shown that intermittent fasting improves insulin sensitivity, thereby reducing insulin resistance (25).
It has been proposed that patients with diabetes may benefit from intermittent fasting. However, studies on the safety and benefits of intermittent fasting with diabetes are very limited.
One study showed intermittent fasting to be easily tolerated in patients with type 2 diabetes (26 .A recent overview of the available scientific knowledge found that intermittent fasting may be beneficial in patients with diabetes (24). Weight loss and reduced insulin requirements are among the benefits achieved.
Results from a recently published study have suggested that three months of intermittent fasting may be able to reverse type 2 diabetes (27).
However, patients with diabetes should use intermittent fasting carefully. Blood sugar has to be monitored and medication adjustments may have to be performed.
The Effects on Heart Disease and Stroke
Coronary artery disease and stroke are common illnesses and frequent causes of early death worldwide.
Measures that improve blood pressure, blood lipids and reduce the risk of diabetes may reduce the risk of these disorders.
Alternate-day fasting in rodent models of obesity has been shown to reduce blood levels of cholesterol and triglycerides (28).
Human studies have shown that fasting lowers total cholesterol, triglycerides, and LDL cholesterol (29,30). Furthermore, the size of LDL particles was increased.
High blood pressure (hypertension) is a common medical disorder that increases the risk of heart disease, stroke, and kidney disorders. It is one of the most important causes of premature death worldwide (31). Animal and human studies suggest that intermittent fasting lowers blood pressure (32, 33).
Animal studies also suggest that intermittent fasting may help to reduce the risk of stroke (34).
Intermittent Fasting and Cancer
Almost 90 years ago, German physician Otto Warburg first posed the question of why cells consume nutrients differently.
Warburg observed that cancer cells seemed to depend on glucose for energy. However, healthy cells can easily cope with glucose deprivation.
The phenomenon was coined “the Warburg effect” and earned Warburg the Nobel Prize in 1931 (35).
Hence, in theory, cancer cells may suffer when glucose is not available, whereas healthy cells will do fine.
Numerous animal studies have shown that caloric restriction and intermittent fasting reduce spontaneous cancers in rodents (1).
Furthermore, intermittent fasting may increase the sensitivity of some cancers to chemotherapy and reduce the side effects of cancer drugs (36). Animal studies suggest that fasting could replace or augment the efficacy of certain cancer drugs (37).
In contrast to most cancer therapies, intermittent fasting only has mild side effects. These may include headaches, dizziness, nausea, weakness, and short-term weight loss (38).
The effects of intermittent fasting on the risk of developing cancer and prognosis after a diagnosis of cancer are unknown because there is a lack of human studies (39). Hence, it is crucial to underscore that clinical research in this area till in its infancy.
Clinical trials of intermittent fasting in patients with cancer are currently in progress.
Effects on Cognitive Function and the Central Nervous System
Studies in animals show that intermittent fasting enhances cognitive function, including memory (40).
In a study involving overweight adults with mild cognitive impairment, caloric restriction led to improvements in verbal memory and other cognitive measures (41).
There is strong evidence from animal studies that fasting can delay the onset of Alzheimer’s disease and Parkinson’s disease (42).
Excessive accumulation of a protein called amyloid-β (Aβ) in the brain is found in patients with Alzheimer’s disease (43). The removal of Aβ has been considered to be crucial in the development of the disease.
One study showed that intermittent fasting seems to protect against Alzheimer’s disease in mice. This may be due to the prevention of Aβ deposition in the brain (44).
In addition, chronic intermittent fasting improves cognitive functions and brain structures in mice (45).
Studies on the effects of intermittent fasting on cognitive function in humans are scarce.
Intermittent Fasting and Inflammation
Inflammation can be both acute and chronic. Acute inflammation is the initial response of the body to harmful stimuli. It is an essential part of bodily defenses and helps to fight off infections. Prolonged or chronic inflammation, on the other hand, is often associated with tissue damage.
When inflammation is appropriate, it protects from disease. When inflammation is inappropriate or gets out of hand, it can cause disease (46).
Inflammation plays a crucial role in many chronic diseases such as heart disease, type 2 diabetes, and many cancers (47).
It is also well-documented that our dietary choices may affect inflammatory responses in the body (48). In a study published recently, Mount Sinai researchers found that fasting reduces inflammation and improves chronic inflammatory diseases (49).
The Effects on Life Expectancy and Aging
Calorie restriction increases both the average lifespan and the maximal lifespan of laboratory animals (50).
One study showed that rats’ average lifespan increased by 80 percent during intermittent fasting (51).
Another study compared mice that were fed one meal per day to mice that were fed freely. The total calorie content was the same for both groups. The mice that were fed one meal per day lived approximately 11 to 14 percent longer. This suggests that time-restricted feeding may contribute to longevity, even in the absence of calorie restriction (52).
During fasting, cells seem to become more able to remove and repair damaged molecules (53).
It has not been scientifically proven that intermittent fasting increases life expectancy in humans.
Intermittent Fasting and Women
It has been suggested that intermittent fasting may affect men and women differently.
Some experts have pointed out that women may be more sensitive to caloric restriction than men. Furthermore, the effects of intermittent fasting on glucose metabolism may vary between men and women.
There have also been anecdotal stories of women who have experienced changes to their menstrual cycles after intermittent fasting (50).
However, there is no scientific data that suggests that intermittent fasting has fewer benefits in women than men. Hence, intermittent fasting appears to be a safe medical intervention that can improve women’s health (51).
Nonetheless, intense fasting is not recommended for pregnant or breastfeeding women.
The Bottom Line
Unfortunately, much of the hype surrounding intermittent fasting arises from animal studies.
To date, there have been no well-controlled scientific studies to determine the effects of long-term intermittent fasting on humans.
Animal studies suggest that intermittent fasting may have several health benefits.
In humans, intermittent fasting helps to promote weight loss, improves insulin resistance and lipid abnormalities, and positively affects hypertension and inflammation.
Although short-term studies are promising, we do not know whether long-term intermittent fasting is effective for weight loss.
Clinical trials of intermittent fasting in patients with cancer are currently in progress.
Animal studies suggest that intermittent fasting may increase life expectancy and promote healthy aging. However, it has not been scientifically proven that intermittent fasting increases life expectancy in humans.
Randomized studies are desperately needed to further assess the possible benefits of intermittent fasting.
The article was initially published January 12, 2020
It was revised, updated and republished on February 6, 2023.
Atherogenic dyslipidemia (AD) is a clinical disorder that, in my opinion, is far too often overlooked. It depicts a blood lipid pattern characterized by elevated triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C). Hence, people with AD have an elevated TG/HDL-C ratio (1).
More crucially, individuals with AD have elevated apolipoprotein B (apoB) levels and their amount of small low-density lipoprotein (LDL) particles is increased,
Atherogenic Dyslipidemia (AD) often tends to be overshadowed by the huge emphasis on modifying low-density lipoprotein cholesterol (LDL-C) However, many individuals with normal LDL-C develop CAD. A large proportion of these patients may have AD.
AD is a common clinical disorder, mostly due to the rapidly increasing prevalence of abdominal obesity and metabolic syndrome.
On top of that, a considerable proportion of patients at risk of coronary events in routine clinical practice have AD. Studies suggest that AD may be present in up to 40% of patients with coronary artery disease (CAD) (2).
Studies show that AD is associated with an increased risk of developing CAD as well as an increased risk of new events in patients who already have established heart disease (3,4).
Unfortunately, AD often tends to be overshadowed by the huge emphasis on modifying low-density lipoprotein cholesterol (LDL-C). However, many individuals with normal LDL-C develop CAD. A large proportion of these patients may have AD.
Diet is the cornerstone of treatment in patients with AD. Evidence suggests that carbohydrate restriction may effectively improve many of the metabolic abnormalities associated with the disorder.
Atherogenic Dyslipidemia is Associated with Other Important Metabolic Abnormalities
Patients with AD frequently have other lipid abnormalities that may help to explain why their risk of atherosclerotic cardiovascular disease is increased.
Above all, ApoB is usually elevated. ApoB is a marker of the amount of all atherogenic lipoprotein particles and is highly associated with the risk of developing CAD (5).
Increased presence of small LDL particles is typically found in people with AD. Studies show that the number of small, dense LDL particles may predict the risk for CAD (6).
Interestingly, the TG/HDL-C ratio may be a valuable predictor of the number of small LDL particles (7).
Altered metabolism of TG-rich lipoproteins is believed to play a key role in AD. There is overproduction and impaired clearance of VLDL from the circulation. There is also slower clearance of chylomicrons derived from the intestines. Hence, increased remnant lipoproteins are often present in high amounts in patients with AD(8).
Remnant lipoproteins, such as very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), may contribute importantly to the risk of atherosclerotic heart disease in patients with AD (9). These remnant lipoproteins typically contain large amounts of TG as well as cholesterol (remnant cholesterol).
When triglycerides are released from VLDL, its composition changes and it becomes IDL. Subsequently, the amount of cholesterol increases and IDL becomes LDL. It is now commonly accepted that small, dense LDL particles are the products of remodeling of TG-rich VLDL particles (10).
In summary, high levels of ApoB, large amounts of small, dense LDL particles, and high levels of TG- and cholesterol-rich remnant lipoproteins may all help to explain why patients with AD are at increased risk of heart disease.
AD is characteristically found in patients with abdominal obesity, metabolic syndrome, and type-2 diabetes (11) Insulin resistance is a common nominator for these disorders. Thus, it is no surprise that AD is sometimes referred to as the dyslipidemia of insulin resistance (12).
Studies indicate that AD is associated with elevated levels of hs-CRP, suggesting continuous low-grade inflammation (13,14). Inflammation plays a major role in the initiation and progression of atherosclerosis.
The Dietary Approach to Atherogenic Dyslipidemia
A very important question is whether and how different diets may improve or worsen the lipid abnormalities associated with AD.
When it comes to the classical question between carbohydrates and fats, there is certainly a lot of evidence suggesting that added sugar and refined carbohydrates are the main drivers of AD (15). High consumption of sugar and refined carbohydrates will promote VLDL production by the liver, a phenomenon, known as carbohydrate-induced hypertriglyceridemia (16). Hence, a high carbohydrate diet may further promote atherogenic dyslipidemia.
Dietary fat, on the other hand, is not a significant source of increased TG-rich lipoproteins and high-fat diets usually don’t raise fasting TG (18).
One study found that moderate carbohydrate restriction and weight loss both improved the lipid abnormalities associated with AD (19).
Another study found that substituting protein for carbohydrate decreased plasma TG in a manner that was independent of saturated fat intake but that reductions in other lipoprotein-related risk factors, including apoB and small LDL, were greatest following consumption of a low-carb-low-saturated-fat diet (20).
Evidence shows that low-fat and low-carbohydrate diets can both be used to induce weight loss. Low- and very low-carbohydrate diets are more effective for short-term weight loss than low-fat diets, although the long-term difference between these two approaches appears similar (21).
