Target cardiovascular risk rather than cholesterol concentration

BMJ 2013; 347 doi: (Published 27 November 2013)
Cite this as: BMJ 2013;347:f7110

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"Tectonic shift" or "Un-masking of an old concept"

I read the editorial by Krumholz(1) with interest that highlights the changes in the recent lipid guidelines and calling these a ‘tectonic shift’. Is this really a ‘tectonic shift’ or is simply the unmasking of the “Diet-Heart: end of an era” concept(2)? As all of the currently used lipid-lowering agents are out of patents and none of the pharmaceutical company has vested interest anymore to influence guidelines or evidence this year. This may change as the new-kid comes on the block (like PCKS9 agents). It appears that the current guidelines were possibly written without a jaundiced view, resulting in unmasking of an old concept that likely was suppressed for 3 decades.


1. Krumholz HM. Target cardiovascular risk rather than cholesterol concentration
BMJ 2013; 347 doi:
2. Mann GV. Diet-Heart: end of an era. NEJM 1977 Sep 22;297(12):644-50.

Competing interests: None declared

Malvinder S. Parmar, MD

Associate Professor, Northern Ontario School of Medicine, 700 Ross Ave. East, Timmins, ON P4N 8P2

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To be specific: the risk of vascular complication, especially stroke, rises exponentially with age.[1] This is why the rigorously designed PROSPER study set out to establish what impact statin therapy had in the highest risk group (the over 70s).[2]

The outcome? No reduction in stroke incidence. There was a reduction in all vascular complications, BUT it needed treatment for nearly 60 people over 3 years to prevent any one vascular complication, or for 100 people over the same duration to prevent one non-fatal vascular complication. And statin therapy brings significant morbidity.[3]

Thus, targeting risk, per se, misses the point. Targeting achievable, evidence-based, and clinically useful outcomes is surely a much more logical approach?

1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22(8):983–988.
2. Shepherd J, Blauw GJ, Murphy MB, Bollen ELEM, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002 Nov;360(9346):1623-1630.
3. Buettner C, Davis RB, Leveille SG, Mittleman MA, Mukamal KJ. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med. 2008 Aug;23(8):1182-1186.

Competing interests: None declared

Kit Byatt, consultant general physician & geriatrician

Hereford County Hospital, Union Walk, Hereford HR1 2ER

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Statins, the final paradigm change: they don’t save lives in a fatal disease.

The Editorial by Krumholz highlights the changes in the recent U.S. cholesterol-treatment guidelines, calling them a tectonic shift, no longer focusing on “cholesterol targets”(1). This shift should precede the final paradigm change when guideline authors, who basically already ignore the term all-cause mortality in a fatal disease, officially also recognize that statins effectively do not lower mortality, a fact certain in women and in anyone over age 70, debated here(2).

While statins lower non-fatal events or visits to the catheterisation laboratory, why don’t they extend lives? Statins minuscule “benefit” may well result from a pleitropic effect such as their undisputed nitroglycerine / nitrate mimicking effect, the NO/eNOS pathways(2). Logically, nitrates should reduce non-fatal event check-marks in Patient-Report-Forms in trials, while also not extending lives. The JUPITER trial was telling because no cardiovascular-deaths were prevented while in women the only statistically significant “benefit” from statin was in fewer visits to the catheterisation laboratory for revascularisations.(3)

The final paradigm shift would be a return to 1977: “end of an era” for the fat and cholesterol Diet-Heart-Hypothesis, that was put on life-support 3 years later by the invent of statins(4). Decades of effort and hundreds of billions wasted to return to what was evident a third of a century ago.

Eddie Vos, M. Eng.
Pierre Biron, M.D.

1. Krumholz HM. Target cardiovascular risk rather than cholesterol concentration
BMJ 2013; 347 doi:

2. Vos E, Rose CP, Biron P. Point: why statins have failed to reduce mortality in just about anybody. J Clin Lipidol. 2013 May-Jun;7(3):222-4.

3. Vos E, Rose CP, Biron P. Doi: 10.1161/circulationAHA.110.954016 Circ 2010 Dec 7;122(23):e576.

4. Mann GV. Diet-Heart: end of an era. NEJM 1977 Sep 22;297(12):644-50.

Competing interests: None declared

Eddie Vos, M.Eng.

Pierre Biron, M.D.

none, maintains, 127 Courser Road, Sutton QC Canada J0E 2K0

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