SAN FRANCISCO – When considering statin therapy for an otherwise healthy patient with elevated cholesterol levels, count the number of cardiovascular risk factors present, Dr. Matthew Sorrentino said.
Even when no single risk factor is way out of line, a "clustering of risk factors" can help identify which patients might most benefit from statin therapy – even if they’re low risk according to Framingham Heart Study criteria or other risk assessment tools.
Dr. Matthew Sorrentino
"It’s really the summation of all of these risk factors together that puts a patient at increased risk," Dr. Sorrentino said at the annual meeting of the American College of Physicians.
He was persuaded by an analysis by other investigators of data from all participants in the Framingham study who had no cardiovascular disease at age 50 years. The lifetime risk for developing cardiovascular disease increased with the number of elevated or major risk factors, from an optimal rate of 5% in men to a rate of 69% in those with two major risk factors, and in women from an optimal rate of 8% to 50% in those with two major risk factors (Circulation 2006;113:791-8).
Dr. Sorrentino gave the example of a patient, a 66-year-old woman, who says she’s worried about her health but has no cardiovascular symptoms. She smokes a few cigarettes a day and has been told in the past that she has borderline or mildly elevated blood pressure. On examination, her blood pressure is 139/92 mm Hg; her body mass index is 30 kg/m2; and fasting lipid results report total cholesterol of 222 mg/dL, a high-density lipoprotein (HDL) level of 42 mg/dL, a triglyceride level of 155 mg/dL, and a low-density lipoprotein (LDL) level of 149 mg/dL*. In sum, she meets three of the five criteria for metabolic syndrome.
By Framingham criteria, she is considered low risk, with an 8% risk for developing cardiovascular disease within 10 years, Dr. Sorrentino noted. But with her cigarette smoking, hypertension, and low HDL – in addition to her elevated LDL level – she has two or more major risk factors, so her lifetime risk for cardiovascular disease is 50%, he said.
"There’s been a lot more interest in thinking about global or lifetime risk," said Dr. Sorrentino, professor of medicine at the University of Chicago. "This can be one way of looking at low-risk patients."
There is some evidence that treating low-risk patients with statins can reduce cardiovascular disease. The best, though controversial, study on the subject was the randomized JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) trial, which found a 44% relative reduction in risk for cardiovascular disease over 5 years in patients treated with the statin, compared with placebo. The study calculated that 25 patients would need to be treated to prevent one myocardial infarction, stroke, revascularization procedure, or cardiovascular death over 5 years (N. Engl. J. Med. 2008;359:2195-2207).
That number needed to treat is similar to findings from two separate primary prevention trials using a statin, and it’s lower than the number needed to treat in many trials of standard blood pressure medications or low-dose aspirin, Dr. Sorrentino said.
Criticism of the JUPITER trial rested on whether it focused on a truly low-risk cohort. Approximately 40% of participants had metabolic syndrome, and 15% smoked, Dr. Sorrentino noted.
That’s why tallying the number of risk factors, as used in the 2008 analysis of lifetime risk, "will be better able to distinguish which low-risk patients would be worthwhile to consider treating," he said.
Dr. Sorrentino has been a speaker for Takeda Pharmaceuticals.
*Correction, 6/28/2013: An earlier version of this story incorrectly reported the hypothetical patient's LDL level.