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Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b92 (Published 16 February 2009) Cite this as: BMJ 2009;338:b92

Rapid Response:

HDL no, LDL yes: wrong conclusion, bad analysis.

It is interesting how a statistical exercise financed by Pfizer about
HDL-cholesterol winds up suggesting that raising HDL does not matter while
lowering LDL-cholesterol does - in cardiovascular events and all-cause
deaths(1).

This study has flaws. First, the exclusion of positive studies not
fitting limiting modeling criteria, like the Coronary Drug Project
regarding niacin vs. placebo and that significantly prevented second heart
attacks with a post-study all-cause mortality benefit(2). No niacin only
study fit the inclusion criteria while niacin (very high dose vitamin B3)
is the undisputed therapy to raise HDL-cholesterol.

On the other hand, the inclusion criteria captured most LDL-lowering
controlled and dose/drug-comparison studies with the sponsor's
atorvastatin (Lipitor), a statin not raising HDL-cholesterol (ASCOT; Table
2 in ref. W40 in (1)) and that never lowered mortality in anyone (W33-W35,
56, W57 in (1)). Moreover, atorvastatin found no "event" benefit in women
(ref. W40 in (1)) as indeed no LDL-lowering study ever found a mortality
benefit in women, including statins(3).

Thirdly, there is no biological rationale for LDL adjustment when
studying HDL since HDL is a blood particle with about 80 (presumably
useful) associated proteins, while "LDL-cholesterol" represents the
concentration of a single-protein lipid transport particle of which the
composition (in trans-fats, omega-3, carotenoids, homocysteine, other)
varies widely depending upon food intakes.

Fourthly, analysis including "events" are confounded by statin's well
known "nitroglycerin mimicking" effect, promoting NO/eNOS, an unadjusted
confounder(4) that may explain, for example, much of the uniquely male non
-fatal event benefit in ASCOT.

The unspoken message of statin benefit, including total deaths, for
all is unsupported by placebo controlled studies where "Numbers Needlessly
Treated" approach infinity regarding all-cause mortality in women, and in
men regarding atorvastatin, while HDL raising niacin therapy remains an
option with trial support. vos{at}health-heart.org

1. Briel M, Ferreira-Gonzalez I, You JJ, Karanicolas PJ, Akl EA, Wu
P, et al. Association between change in high density lipoprotein
cholesterol and cardiovascular disease morbidity and mortality: systematic
review and meta-regression analysis. BMJ. 2009 Feb 16;338:b92. Medline
19221140
http://www.bmj.com/cgi/content/full/338/feb16_1/b92

2. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ,
et al. Fifteen year mortality in Coronary Drug Project patients: long-term
benefit with niacin. J Am Coll Cardiol. 1986 Dec;8(6):1245-55. Medline
3782631

3. Walsh JME, Pignone M. Drug Treatment of Hyperlipidemia in Women.
JAMA. 2004;291:2243-2252. Medline 15138247
http://jama.ama-assn.org/cgi/content/full/291/18/2243

4. Laufs U. Beyond lipid-lowering: effects of statins on endothelial
nitric oxide. Eur J Clin Pharmacol. 2003 Mar;58(11):719-31. Medline
12634978

Competing interests:
None declared

Competing interests: No competing interests

03 March 2009
Eddie Vos
maitains health-heart.org
Sutton (Qc) Canada J0E 2K0