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Editor's Note
September 22, 2021

Transforming the Paradigm for Lipid Lowering

Author Affiliations
  • 1Clinical Heart and Vascular Center, University of Texas Southwestern Medical Center, Dallas
  • 2Associate Editor, JAMA Cardiology
  • 3Ahmanson-UCLA (University of California, Los Angeles) Cardiomyopathy Center, David Geffen School of Medicine, UCLA
  • 4Section Editor, JAMA Cardiology
JAMA Cardiol. 2021;6(12):1414. doi:10.1001/jamacardio.2021.3517

Decades of research have demonstrated that low-density lipoprotein cholesterol (LDL-C) is a causative factor in the development of atherosclerotic cardiovascular disease, and lipid-lowering therapy can dramatically reduce this risk. Yet exactly when to begin lipid-lowering therapy has not been well demarcated. Atherosclerotic lesions develop slowly over many years, if not decades. However, guidelines for lipid management have largely recommended statins on the basis of a 10-year risk of cardiovascular events rather than the risk of developing atherosclerosis over a lifespan. As a result, young adults (aged <40 years) are eligible for statins only if they have familial hyperlipidemia, severely elevated LDL-C level (>190 mg/dL; to convert to millimoles per liter, multiply by 0.0259) or LDL-C of 160 mg/dL or higher, and a family history of premature atherosclerotic cardiovascular disease.1

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2 Comments for this article
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Transforming the Paradigm for Lipid Loweringg
John Stein, M.D. | West County Preventive Medical Care
I applaud Drs. Navar and Fonarow call for a more comprehensive approach to the totality of evidence in preventing ASVCD. What we currently provide is far too late in disease progression, necessitating more costly therapies with less return on investment. Smaller and earlier generic interventions may reduce the initial and requisite ASCVD steps of subendothelial accumulation of apolipoprotein B. This paradigm shift is far overdue for our caregivers and patients.
CONFLICT OF INTEREST: None Reported
Statins and Brain Function
John Woodall, MD | Synergy Health Services, Newtown, CT
Statins inhibit cholesterol production by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) which blocks the conversion of mevalonic acid to farnesyl pyrophosphate. In doing so three biochemical pathways that branch from farnesyl pyrophosphate are inhibited that lead variously to the production of cholesterol, the ubiquinones (CoEnzymeQ10 in particular) and dolichol. CoEnzymeQ10 is an indispensable cofactor in the electron transport chain necessary to move electrons from Complex I and II in the inner membrane of the motochondria to ultimately fuel the proton pump, ATP Synthase, that produces ATP.
While it is true that multiple studies(1,2) have shown that the use of statins
does not increase the incidence of vascular causes of dementia, multiple studies show a direct link between the use of statins and cognitive decline, likely as a result of the depletion of ATP energy stores from the inhibition of CoEnzymeQ10 (3,4,5,6) and possibly the loss of cellular anchoring stability due to the depletion of dolichol. Cognitive decline as a result of statin use has been the subject of considerable research. (3,4,5,6,7)
In my practice as a psychiatrist, it is not uncommon for me to see elderly patients on statins who present with signs of energetic depletion: poor concentration, fatigue, poor endurance, "brain fog" and depression who subsequently benefit from repletion of CoEnzymeQ10 by supplementation. (7,8,9).



1.) O'Brien EC, Greiner MA, Xian Y, Fonarow GC, Olson DM, Schwamm LH, et al. (13 October 2015). "Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study". Circulation. 132 (15): 1404–1413. doi:10.1161/CIRCULATIONAHA.115.016183. PMID 26246175. S2CID 11252336.
2.) Mijajlović MD, Pavlović A, Brainin M, Heiss WD, Quinn TJ, Ihle-Hansen HB, et al. (January 2017). "Post-stroke dementia – a comprehensive review". BMC Medicine. 15 (1): 11.
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CONFLICT OF INTEREST: None Reported
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