Author + information
- Kirti Kain, MD∗ ()
- ↵∗Division of Cardiovascular & Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds LS2 9JT, United Kingdom
The paper by Mortensen et al. (1) compares American College of Cardiology/American Heart Association risk-based versus trial-based approaches for primary prevention with statins (1). The investigators acknowledged the limitation that only white subjects were studied, and therefore, the results do not necessarily apply to other ethnicities. This is the case especially for South Asians (people originally from India, Pakistan, or Bangladesh).
Statins are potent, specific, competitive inhibitors of microsomal enzyme 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase, which upregulates low-density lipoprotein (LDL) receptors and cholesterol uptake. Statins also reduce mRNA and protein expression of GLUT2, which limits glucose uptake and inhibits L-type calcium channels that are required for insulin secretion. Statin-related muscle side effects are common and contribute significantly to rates of nonadherence. High-potency statins are associated with a moderate increase in the risk of new-onset diabetes.
The U.S. Food and Drug Administration has approved the first 2 PCSK9-inhibiting drugs to help lower levels of LDL cholesterol, which is linked to cardiovascular disease. PCSK9-deficient mice have been found to be hypoinsulinemic and glucose intolerant.
South Asians have increased rates of ischemic heart disease and ischemic stroke, and their adverse cardiometabolic risk profile differs from that of the Europeans. The principle cardiovascular disease risk factor is decreased insulin sensitivity because of decreased activity and/or visceral obesity, which results in abnormal glucose status along with increased triglycerides and decreased high-density lipoprotein cholesterol. Moreover, mean LDL concentrations are lower in South Asians compared with Europeans (2). South Asians experience increased aches and muscle pains compared with the Europeans when taking statin drugs (3).
Therefore, indiscriminate use of statins in South Asians can worsen their insulin resistance and quality of life (i.e., increased aches and pains). Likewise, the Afro-Caribbean population does not have an unfavorable lipid risk profile and has decreased ischemic heart disease, but they also have increased insulin resistance.
Researchers reviewed 305 randomized controlled trials and concluded there were “no statistically detectable differences” between physical activity and medications for heart disease (4). An acute bout of exercise increases skeletal muscle glucose uptake, whereas long-term exercise training improves mitochondrial function (5).
The human body has many sets of interdependent molecular-cogged wheels within its cell and intercellular mechanisms. If one cog ruptures or becomes dysfunctional (increased LDL cholesterol), it might be appropriate to fix it with an appropriate site and/or function cog (drug) for secondary prevention. However, is it reasonable to insert an extra cog (statin) as a primary preventative measure for generalized rusting (arteriosclerosis or atherosclerosis) when it might have detrimental effects on other cogs or their functions on the same cogwheel or other cogwheels (new-onset diabetes and aches and/or pains)?
Please note: Dr. Kain has reported that she has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Mortensen M.B.,
- Afzal S.,
- Nordestgaard B.G.,
- Falk E.
- Karthikeyan G.,
- Teo K.K.,
- Islam S.,
- et al.
- Palmer B.,
- Macfarlane G.,
- Afzal C.,
- Esmail A.,
- Silman A.,
- Lunt M.
- Naci H.,
- Ioannidis J.P.
- Stanford K.I.,
- Goodyear L.J.