Statin therapy and physical fitness amounted to a one-two punch for lowering mortality risk in a large cohort of middle-age and older patients with dyslipidemia followed for 10 years.
Patients who took statins and were physically fit had as much as a 70% reduction in the risk of dying during the follow-up period as compared with the least physically fit patients who were taking statins, according to Peter Kokkinos, PhD, of George Washington University in Washington, and colleagues.
Physical fitness also had an independent effect on mortality risk among patients who were not taking statins, reducing the likelihood of death during follow-up by as much as 47%, they reported online in The Lancet.
"Statin treatment and increased fitness are independently associated with low mortality among dyslipidemic individuals," the authors wrote. "The combination of statin treatment and increased fitness resulted in substantially lower mortality risk than either alone, reinforcing the importance of physical activity for individuals with dyslipidemia."
Expert and consensus panels on lipid management have endorsed statin therapy and lifestyle changes, including increased physical activity, to reduce cardiovascular risk. The benefits of statins have been demonstrated in multiple large clinical trials, and evidence from large epidemiologic studies has shown robust inverse associations between physical fitness and mortality risk in healthy individuals and those with cardiovascular disease.
Studies to date have provided limited information about the combined effects of statins and physical fitness on mortality risk or other clinical events. No study has evaluated the potential of increased fitness to lower mortality risk in dyslipidemic patients who cannot take statins, the authors noted.
To evaluate the combined effects of fitness and statin therapy on mortality risk, Kokkinos and colleagues identified dyslipidemic patients who had exercise tolerance tests at two Veterans Affairs medical centers during 1986 to 2011. Investigators rated each patient's fitness on the basis of metabolic equivalents (METs).
The primary endpoint was all-cause mortality, adjusted for age, body mass index (BMI), ethnicity, sex, and history of cardiovascular disease, drug therapy, and risk factors.
The search of medical records identified 10,043 patients, who had a mean age of 59, mean BMI of about 29 kg/m2, and peak MET of 7.4. The cohort comprised 5,046 statin users and 4,997 who were not taking statins.
Statin users tended to be older and had lower exercise capacity, higher BMI, and higher rates of cardiovascular disease, risk factors, and use of cardiovascular drugs.
The lipid profile for statin users at baseline and after a median treatment period of 70 months was:
- Total cholesterol: 238 mg/dL and 172 mg/dL
- High-density lipoprotein (HDL): 47 mg/dL for both time points
- Low-density lipoprotein (LDL) 164 mg/dL and 101 mg/dL
- Triglycerides: 142 mg/dL and 134 mg/dL
In the nonstatin group, the lipid profile at baseline and at last follow-up with lipid assessment (median 51 months) was:
- Total cholesterol 234 mg/dL and 199 mg/dL
- HDL: 47 mg/dL for both time points
- LDL: 156 mg/dL and 140 mg/dL
- Triglycerides: 134 mg/dL and 134 mg/dL
During median follow-up of 10 years, 2,318 patients died. The statin group had an overall mortality of 18.5% compared with 27.7% among patients not taking statins (P<0.0001).
Mortality decreased with increasing physical fitness in both groups. In the statin group, the most-fit patients (>9 METs) had 70% lower mortality risk compared with the least-fit (≤5 METs) patients (P<0.0001). In the nonstatin group, the least-fit subgroup had a 35% increase in the mortality hazard (P<0.0001), whereas the most-fit members of the group had a 47% reduction in the hazard ratio (P<0.0001).
For the entire cohort, each 1 MET increase in exercise capacity was associated with a 12% reduction in the mortality hazard (17% in the statin group, 11% in the nonstatin group).
The study had some limitations, most notably the male veteran patient population, making it difficult to generalize the results to women. Also, the authors did not have data for cardiovascular interventions or cardiovascular mortality. Finally, there was no data on adverse effects of statins especially if the treatment interfered with exercise capacity.
In an accompanying commentary, Pedro Hallal, PhD, from the Federal University of Pelotas in Rio Grande do Sul, Brazil and I-Min Lee, MD, from Harvard Medical School in Boston said that the prescription of physical activity should be placed on a par with drug prescription.
"The cost of becoming physically active is lower than that of buying drugs, and moderate intensity physical activity has fewer side effects" they pointed out. "Unlike statins, physical activity should be part of everyday life."