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.

Assessing cardiovascular disease: looking beyond cholesterol.

Purpose Of Review: The low-density lipoprotein (LDL)-cholesterol level is a weak predictor of developing cardiovascular (CV) disease and can only explain a small proportion of CV risk. It is not used to determine CV risk on either the atherosclerotic cardiovascular disease (ASCVD) calculator in the United States, or the Qrisk3 in the UK.A study in JAMA in 2022 suggested that ' the absolute benefits of statins are modest and may not be strongly mediated through the degree of LDL reduction '.

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.

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.

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.

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.

Objective: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.

Setting, Participants And Outcome Measures: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.

Results: We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts.

Should women be offered cholesterol lowering drugs to prevent cardiovascular disease? No.

Women in western countries are more likely to die from heart disease than from cancer.argues that the risks make preventive treatment essential, but believes the evidence of benefit is not strong enough

Does insulin resistance cause atherosclerosis in the post-prandial period?

Insulin resistance would appear to be a causal factor for the development of early occlusive atherosclerosis. This paper proposes that post-prandial insulin resistance, in association with raised levels of cortisol and catecholamines, plays the major role, and may even be the primary causative factor. Therefore, factors that lead to insulin resistance in the post-prandial period, specifically stress, will accelerate the development of CHD.