[Skip to Navigation]
Views 9,347
Citations 0
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. Published online September 22, 2021. 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

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    2 Comments for this article
    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.
    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.
    1. Litarru G. P., Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37:31–37. [PubMed] [Google Scholar]
    2. Siciliano G., Volpi L., Piazza S., Ricci G., Mancuso M., Murri L. Functional diagnostics in mitochondrial diseases. Biosci Rep. 2007;27((1–3)):53–67. [PubMed] [Google Scholar]
    3. Constantinescu R., McDermott M. P., DiCenzo R., et al. A randomized study of the bioavailability of different formulations of coenzyme Q10 (ubiquinone) J Clin Pharmacol. 2007;47((12)):1580–1586. Epub 2007 Oct 9. [PubMed] [Google Scholar]
    4. Littarru G. P., Langsjoen P. Coenzyme Q10 and statins: biochemical and clinical implications. Mitochondrion. 2007;7((suppl)):S168–S174. Epub 2007 March 27.
    5. Run3.) Rojas-Fernandez CH, Cameron JF. Is statin associated cognitive impairment clinically relevant? A narrative review and clinical recommendations. Ann Pharmacother. 2012;46(4):549–557.
    6.) Padala KP, Padala PR, Potter JF. Simvastatin induced decline in cognition. Ann Pharmacother. 2006;40(10):1880–1883.
    7.) Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA. Treatment of statin adverse effects with supplemental co-enzyme Q10 and statin discontinuation. Biofactors. 2005;25(1–4):147–152.
    8.) Shetty RA, Forster MJ, Sumien N. Co-enzyme Q10 supplementation reverses age-related impairment in spatial learning and lowers protein oxidation. Age (Dordo) 2013;35(5):1821–1834.
    9.)Nawarskas JJ. HMG-CoA reductase inhibitors and co-enzyme Q 10. Cardiol Rev. 2005;13(2):76–79.