Annette M. Boyle
WASHINGTON–With strong evidence that a combination of exercise and cholesterol-lowering drugs creates a potent weapon against deaths from heart disease, VA researchers are grappling with a related issue: What is the correct amount of each?
They already know that more is not necessarily better.
Statins and exercise both significantly and independently lower cholesterol, and combining the two can reduce all cause mortality by 70%, according to a study recently published in The Lancet.1
The prospective study included 10,043 patients with dyslipidemia treated at the Veterans Affairs Medical Centers in Palo Alto, CA, and Washington. The average age of participants was 58.8 years; 9.700 were men and 343 were women. All participants were assigned to one of four fitness categories — least, moderate, fit or high — based on peak metabolic equivalents (MET) achieved during an exercise test administered between 1986 and 2011. Researchers followed participants for a mean of 10 years, during which time nearly 25% (2318) died.
Mortality risk for patients who used statins was 18.5% compared to 27.7% for those who did not using the cholesterol-lowering drugs. Among statin users, mortality risk plummeted as fitness rose, with the most fit group having a death rate 70% lower than the least fit. Fit patients who were not on statins had a 50% lower mortality risk than the least fit patients on statins.
“The most unfavorable combination was low exercise capacity and lack of statin therapy,” wrote the researchers.
While the study did not compare groups of patients who were not on statins, “low-fit patients who were not taking statins had 2 to 2.5 times the risk of the patients in the highest fit group who were not on statins,” lead researcher Peter Kokkinos, PhD, FAHA, FACSM, director, LIVe Program, Washington DC VAMC, told U.S. Medicine.
Protective at All Fitness Levels
“If fitness alone can cut the death rate in half, we have an effective, inexpensive approach to defend against premature death, regardless of statin therapy. We are not suggesting that exercise or fitness takes the place of statins,” said Charles Faselis, MD, chief of medicine at the Washington VAMC and co-author of the study. The best results were seen in patients who took statins and were physically fit; but at all levels of fitness, statin use was independently associated with lower mortality risk.
National and VA guidelines for prevention and secondary prevention of cardiovascular disease recommend statins as a mainstay of treatment for high- and moderate-risk patients, said Faselis. “But those who can’t take statins because of side effects should really look at exercise as an effective way to reduce risk.”
The level of fitness found to be protective can be achieved by brisk walking for 30 minutes per day or 150 minutes per week. Kokkinos noted that with exercise, more is not always better.
“There appears to be a minimum threshold of about 60 minutes or 30 minutes twice a week below which exercise provides little benefit. Between 60 minutes and 120 minutes, the benefits quadruple. Beyond 200 minutes, though, nothing really happens; there is no additional benefit.”
Similarly, increases in intensity of exercise may not improve health beyond the results seen with brisk walking. “There are some benefits associated with greater intensity, say, running vs. walking, but running is also associated with great injury. Brisk walking has the best risk-benefit ratio,” Kokkinos added.
In a related study, researchers found that higher doses of statins might not be better than moderate doses — and that up to 14% of diabetic patients with dyslipidemia may be overtreated.
That study, published in Circulation: Cardiovascular Quality and Outcomes, questions the wisdom of the “lower is better” goals for low-density lipoprotein (LDL) levels in all patients with diabetes mellitus and instead encourages adoption of a more individualized approach to treatment.2
Many national performance measures have considered a LDL below 100 mg/dl for diabetic patients to be evidence of quality treatment.
“The treat-to-target approach promotes the use of high-dose statins in all patients who do not achieve targets with lower doses. Furthermore, attempting to achieve stated targets will often require the use of nonstatin LDL-lowering therapy (e.g., fibrates, ezetimibe or niacin) that have not been shown to benefit outcomes, particularly when combined with statins,” the authors wrote.