Worth noting is that prehypertension may be a powerful prognosticator of metabolic syndrome, which is considered a major pathway to CVD. Therefore, a more selective approach to treatment of prehypertension might factor in recognition of concomitant risk factors pointing to insulin resistance, such as borderline glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and mid-abdominal weight gain. Merely lowering BP with medication would be expected to partially ameliorate risk, but a more comprehensive approach with diet and exercise might more fundamentally address the underlying metabolic dysfunction.
Lipid-lowering therapy is firmly entrenched as a means of preventing CVD. But many researchers and health-care providers argue that lipid lowering for primary prevention is merely a poorly justified extrapolation of its benefits in patients with established coronary artery disease (CAD). Considerable evidence supports the prescription of statins in patients with proven CAD (status post MI, angioplasty, or coronary artery bypass) or with angina or documented plaque burden. But based on a meta-analysis of 14 studies comprising more than 34,000 patients, the prestigious Cochrane Collaboration recently concluded:
“Widespread use of statins in people with low risk of cardiovascular events—below a 1% all-cause mortality risk or an annual CVD event rate of 2% observed in the control groups in the trials considered here—is not supported by the existing evidence.”12
An article by John Carey makes the point another way: Citing a direct-to-consumer ad for atorvastatin (Lipitor), which claims a heart disease reduction of 36%, the author notes that by Pfizer’s own admission, this translates at best to a reduction in CVD events from three per 100 untreated controls to two per 100 in the treatment arm.13 This, he notes, adds up to an NNT of 100: 99 individuals would have to be treated for a minimum of three years to prevent one person from developing CVD. The study often cited in support of using cholesterol drugs is an industry-sponsored trial that includes carefully selected, high-risk patients with risk factors like high BP and smoking.
Other government-sponsored trials of statins yield less robust results, pegging the NNT at 250 (or higher) even if patients take the drugs for five years or more. “Anything over an NNT of 50 is worse than a lottery ticket; there may be no winners,” argues Nortin M. Hadler, professor of medicine at the University of North Carolina at Chapel Hill.13
The key to better deployment of statins in primary prevention may lie in better risk stratification. Current LDL guidelines, variously adhered to or ignored by clinicians, may be reductive and overly simplistic. In a comprehensive review of CVD prevention strategies, Hobbs writes:
“Although high [LDL] may be the most important individual risk factor for [CHD], estimation of an individual’s actual risk for future CHD events must take into account all other coexistent CHD risk factors. Indeed, risk associated with any level of cholesterol is notably influenced by coexistent risk factors. . . [A]n individual with a number of modest risk factors may be at considerably greater risk for CHD than a person with one very high risk factor.”14
Accordingly, the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study highlighted another readily measurable parameter as signaling risk and qualifying patients for statin intervention.15 Individuals with elevated levels of high-sensitivity C-reactive protein (hs-CRP) were found to be potential beneficiaries of statins, even when cholesterol levels were normal or low by National Cholesterol Education Program and American Heart Association criteria.
If correct, the implication is that an additional 20 million or more Americans without high cholesterol whose hs-CRP level is >2.0 mg/L might be candidates for statins. Still, even in those with elevated hs-CRP values, absolute risk is extremely low. Applying the hazard ratios from the JUPITER study, the NNT with rosuvastatin to prevent one coronary event was unacceptably high.