TLDR: The current advice that LDL is “bad cholesterol”, appears to be outdated, and the actual situation is more complex. In people over 60 high LDL appeared to be protective for mortality.

Conclusions: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Full Paper at https://pubmed.ncbi.nlm.nih.gov/27292972/

Related to, and following up on the LMHR paper from https://hackertalks.com/post/5835924

  • jetOPMAEnglish
    1·
    8 days ago

    20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia

    I read the paper, thanks for the link! I found it interesting.

    The basis of the available evidence, the LDL hypothesis is no longer a hypothesis and can be considered a fact.16,17 In addition, mendelian randomization studies show that the consequences of LDL cholesterol with respect to the development of atherosclerotic vascular disease are determined not only by the absolute LDL cholesterol level but also by the cumulative exposure of the arterial wall to LDL cholesterol

    The paper doesn’t make it clear if this is a statement with respect to FH, or humans in general. One caveat that comes to mind is this statement is lumping in all types of LDL

    It is caused by mutations in genes encoding key proteins involved in the low-density lipoprotein (LDL) receptor endocytic and recycling pathways that lead to decreased cellular uptake of LDL cholesterol.

    From the introduction of the paper, they define FH as miscoded lipoproteins. I’m not sure the LDL in FH is compatible to non-miscoded LDL (normal people, not glycated, or oxidized), at least in so far as making the first statement a “fact”

    From Non-coronary heart disease mortality and risk of fatal cancer in patients with treated heterozygous familial hypercholesterolaemia: a prospective registry study - Full paper is on scihub

    Admittedly this study is 10 years older

    table 3

    Table 5 is also really interesting.

    although coronary mortality remained elevated with statin treatment, all-cause mortality after 1991 did not differ from that of the general population. This was due mainly to an unanticipated 50% decrease in the risk of fatal cancer.

    After statin availability subjects with FH appear to have less cancers then the general population. I wonder if this suggests that while very high LDL can be a CVD risk factor, could it also be a cancer risk factor? The authors suggest the cancer reduction is due to lifestyle advice given, but I think it could be suggestive of a impact of LDL. Or was the elevated LDL while being treated with statins protective?