Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia.

For almost a century, familial hypercholesterolemia (FH) has been considered a serious disease, causing atherosclerosis, cardiovascular disease, and ischemic stroke. Closely related to this is the widespread acceptance that its cause is greatly increased low-density-lipoprotein cholesterol (LDL-C). However, numerous observations and experiments in this field are in conflict with Bradford Hill's criteria for causality.

Serious flaws in targeting LDL-C reduction in the management of cardiovascular disease in familial hypercholesterolemia.

Recently, Polychronopoulos and Tziomalos reviewed research on the use of inclisiran and bempedoic acid in the management of cardiovascular disease (CVD) risk in people with familial hypercholesterolemia (FH). Their treatment recommendations were based on the general premise that high LDL-cholesterol (LDL-C) is inherently atherogenic, and that low levels of LDL-C need to be achieved to reduce CVD risk in FH individuals. However, their perspective on LDL-C is flawed at two levels of analysis: 1) They ignored the extensive literature demonstrating that CVD is not caused by high LDL-C; and 2) they failed to consider CVD treatment strategies that take into account the extensive literature that has shown that coagulation factors are more closely related to coronary events in FH than is LDL-C.

The new European guidelines for prevention of cardiovascular disease are misleading.

: The European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have recently published three major revisions of their guidelines for the management of chronic heart disease, blood lipids, and diabetes. : We have scrutinized these guidelines in detail and found that the authors have ignored many studies that are in conflict with their conclusions and recommendations. : The authors of the guidelines have ignored that LDL-cholesterol (LDL-C) of patients with acute myocardial infarction is lower than normal; that high cholesterol is not a risk factor for diabetics; that the degree of coronary artery calcification is not associated with LDL-C; and that 27 follow-up studies have shown that people with high total cholesterol or LDL-C live just as long or longer than people with low cholesterol.

Hit or miss: the new cholesterol targets.

Drug treatment to reduce cholesterol to new target levels is now recommended in four moderate- to high-risk patient populations: patients who have already sustained a cardiovascular event, adult diabetic patients, individuals with low density lipoprotein cholesterol levels ≥190 mg/dL and individuals with an estimated 10-year cardiovascular risk ≥7.5%. Achieving these cholesterol target levels did not confer any additional benefit in a systematic review of 35 randomised controlled trials.

Dietary Recommendations for Familial Hypercholesterolaemia: an Evidence-Free Zone.

We have evaluated dietary recommendations for people diagnosed with familial hypercholesterolaemia (FH), a genetic condition in which increased low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk for coronary heart disease (CHD). Recommendations for FH individuals have emphasised a low saturated fat, low cholesterol diet to reduce their LDL-C levels. The basis of this recommendation is the 'diet-heart hypothesis', which postulates that consumption of food rich in saturated fat increases serum cholesterol levels, which increases risk of CHD.

Formal comment on "Systematic review of the predictors of statin adherence for the primary prevention of cardiovascular disease".

Statins have been prescribed for primary prevention of cardiovascular disease (CVD) for nearly 3 decades. Throughout this period key opinion leaders in the field have been dismayed by the high rate of non-adherence of patients to follow their statin regimen. Hope et al.

New and traditional foods in a modernized Mediterranean diet model.

Mediterranean diet is definitely one of the healthiest dietary models. Next questions are: is the traditional Mediterranean diet adapted to the modern environmental and existential conditions? Could and/or should it be "modernized" to adapt to the various geographical, environmental, ethnic, and religious characteristics? If "modernization" is required, which traditional Mediterranean foods should be imperatively conserved as they are? Alternatively, which "new" foods-not traditional or not Mediterranean-could be introduced to help people to still respect the basic healthy Mediterranean diet principles? The present article intends to help solving these new questions.

Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.

High low-density-lipoprotein cholesterol (LDL-C) is routinely described as the main cause of cardiovascular disease (CVD) in familial hypercholesterolemia (FH). However, numerous observations are in conflict with Bradford Hill's criteria for causality: a) degree of atherosclerosis is not associated with LDL-C; b) on average the life span of people with FH is about the same as for other people; c) LDL-C of people with FH without CVD is almost as high as in FH patients of the same age with CVD; and d) questionable benefit or none at all have been achieved in the controlled, randomized cholesterol-lowering trials that have included FH individuals only. Obviously, those individuals with FH who suffer from CVD may have inherited other and more important risk factors of CVD than high LDL-C.

LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature.

For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma.

Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect.

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats.

A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose. The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk.

Whole Rye Consumption Improves Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats.

Background: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition.

Cholesterol confusion and statin controversy.

The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD.

Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats.

Methods: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA]) increased the very-long-chain omega-3 fatty acids (VLC n-3) [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in rats. Wheat aleurone (WA) was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP) in presence of linseed oil (LO) to provide alpha-linolenic acid (ALA), the precursor of VLC n-3.

Definitions and potential health benefits of the Mediterranean diet: views from experts around the world.

The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet.

Folate intake and folate serum levels in men and women from two European populations: The IMMIDIET project.

Objective: Folate status has been associated with neural tube defects and cerebrovascular disease. The aim of this study was to evaluate possible differences in folate status in two European Union countries and to assess their possible association with dietary patterns and/or other lifestyles.

Methods: In the framework of the European Union-funded IMMIDIET Project, 1068 individuals (534 male-female pairs), ages 26 to 64 y, were enrolled in Italy and the United Kingdom.

Bioavailability and metabolism of hydroxycinnamates in rats fed with durum wheat aleurone fractions.

The consumption of wholemeal cereals has been associated with the reduced risk of several chronic diseases, and the mechanisms behind these protective effects may be linked, besides dietary fiber and micronutrients, to an increased intake of hydroxycinnamates contained in the bran. Among bran fractions, aleurone usually contains the highest concentration of ferulic acid and diferulic acid esters linked to arabinoxylans representing the most relevant subclasses. The aim of the present study was to evaluate the absorption of hydroxycinnamates by measuring the urinary metabolite profiles of rats fed with the two different aleurone fractions (the inner part of the aleurone, named wheat aleurone A, WA-A, and the outer part, named wheat aleurone B, WA-B).

Do statins increase and Mediterranean diet decrease the risk of breast cancer?

Background: Physical exercise and healthy dietary habits are recommended to prevent breast cancer.

Discussion: Increased intake of omega-3 fatty acids associated with decreased omega-6 - resulting in higher omega-3 to omega-6 ratio compared with Western-type diet - is inversely associated with breast cancer risk. The modernized Mediterranean diet with high omega-3 to omega-6 ratio, high fiber and polyphenol intake, and consumption of low-glycemic index foods reduces overall cancer risk and specifically breast cancer risk.

Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors.

In addition to genetic predisposition and sex hormone exposure, physical activity and a healthy diet play important roles in breast cancer (BC). Increased intake of omega-3 fatty acids (n-3) associated with decreased omega-6 (n-6), resulting in a higher n-3/n-6 ratio compared with the western diet, are inversely associated with BC risk, as shown by Yang et al. in their meta-analysis in BMC Cancer.

Gluten and wheat intolerance today: are modern wheat strains involved?

Celiac disease is a food-induced enteropathy resulting from exposure to gluten in genetically predisposed individuals. The non-celiac gluten sensitivity (NCGS) is a less known syndrome whose prevalence is under-estimated. The last decades have seen changes in the clinical presentation of both diseases.