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

Abstract

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. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis. Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.

Baseline plasma lipid levels in patients with acute coronary syndrome: Association with 20‐year mortality. The ABC‐5a* Study on Heart Disease

“…Low or normal TC and LDL‐C in patients with CVD has been reported by other researchers 19,20 . Recently, the general view has been questioned 5‐7 . As reported by Ravnskov et al, 7 there are many observations and experiments contradicting that high TC or LDL‐C causes atherosclerosis and CVD, and several recent observations have supported their view.…”

“…In many studies, increased serum lipids and lipoproteins are associated with a higher risk of total and cardiac mortality 27‐35 . However, absence of an association, or even an inverse association, has been reported, 5‐7 especially with increasing age 26,36 . In accordance, prior observational studies have reported paradoxically better outcomes in hypercholesterolaemic patients who sustain acute coronary syndrome, the so‐called ‘cholesterol paradox’ 20,37‐39 …”

“…Recently, the general view has been questioned 5‐7 . As reported by Ravnskov et al, 7 there are many observations and experiments contradicting that high TC or LDL‐C causes atherosclerosis and CVD, and several recent observations have supported their view. For instance, six recent follow‐up studies including almost 700 000 individuals of all ages from various countries have shown that neither TC nor LDL‐C is a risk factor of mortality, neither among statin‐treated patients nor among untreated individuals 21‐25 .…”

“…High plasma lipid levels, particularly total serum cholesterol (TC) and low‐density lipoprotein (LDL), have long been recognised as a major risk factor for atherosclerosis and IHD 2‐4 . However, this causal relationship has been debated in recent reports 5‐7 . The prognostic value of admission plasma lipid levels in patients presenting with acute coronary syndrome has rarely been discussed in the literature 8‐10 .…”

Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians

“…Focusing on plasma lipids, the positive association between total cholesterol (TC) and cardiovascular risk is strong in middle-aged adults, but it becomes weaker in those with 80 years of age or older (5). In addition, we recently reported that high LDL cholesterol (LDL-C) levels are not associated to subclinical coronary artery disease in healthy octogenarians (6) and results of a recent meta-analysis showed either a lack or an inverse association between LDL-C and both all-cause and CVD mortality in the late-life age (7).…”