Elsevier

The Lancet

Volume 381, Issue 9864, 2–8 February 2013, Pages 394-399
The Lancet

Articles
Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: a cohort study

https://doi.org/10.1016/S0140-6736(12)61426-3Get rights and content

Summary

Background

Statins are commonly prescribed for management of dyslipidaemia and cardiovascular disease. Increased fitness is also associated with low mortality and is recommended as an essential part of promoting health. However, little information exists about the combined effects of fitness and statin treatment on all-cause mortality. We assessed the combined effects of statin treatment and fitness on all-cause mortality risk.

Methods

In this prospective cohort study, we included dyslipidaemic veterans from Veterans Affairs Medical Centers in Palo Alto, CA, and Washington DC, USA, who had had an exercise tolerance test between 1986, and 2011. We assigned participants to one of four fitness categories based on peak metabolic equivalents (MET) achieved during exercise test and eight categories based on fitness status and statin treatment. The primary endpoint was all-cause mortality adjusted for age, body-mass index, ethnic origin, sex, history of cardiovascular disease, cardiovascular drugs, and cardiovascular risk factors. We assessed mortality from Veteran's Affairs’ records on Dec 31, 2011. We compared groups with Cox proportional hazard model.

Findings

We assessed 10 043 participants (mean age 58·8 years, SD 10·9 years). During a median follow-up of 10·0 years (IQR 6·0–14·2), 2318 patients died, with an average yearly mortality rate of 22 deaths per 1000 person-years. Mortality risk was 18·5% (935/5046) in people taking statins versus 27·7% (1386/4997) in those not taking statins (p<0·0001). In patients who took statins, mortality risk decreased as fitness increased; for highly fit individuals (>9 MET; n=694), the hazard ratio (HR) was 0·30 (95% CI 0·21–0·41; p<0·0001) compared with least fit (≤5 METs) patients (HR 1; n=1060). For those not treated with statins, the HR for least fit participants (n=1024) was 1·35 (95% CI 1·17–1·54; p<0·0001) and progressively decreased to 0·53 (95% CI 0·44–0·65; p<0·0001) for those in the highest fitness category (n=1498).

Interpretation

Statin treatment and increased fitness are independently associated with low mortality among dyslipidaemic individuals. 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 dyslipidaemia.

Funding

None.

Introduction

Results of several clinical trials have shown that statin treatment substantially reduces morbidity and mortality of individuals with coronary heart disease.1, 2, 3 On the basis on these findings, the Adult Treatment Panel 3 and other expert panels have issued guidelines4 for statin treatment of patients with established coronary heart disease.5 Trials also suggest that statin treatment provides health benefits for individuals with high risk of cardiovascular disease who do not have coronary heart disease.6, 7, 8, 9

Expert panels on management of lipids have also emphasised the importance of lifestyle changes for reduction of cardiovascular risk.4, 5 These recommendations are based on evidence from large epidemiological studies. Data from these studies show inverse, graded, independent, and robust associations between physical activity (fitness) and mortality risk in apparently healthy participants10, 11, 12, 13, 14, 15, 16 and in patients with cardiovascular disease, irrespective of age, sex, or comorbidities.14, 17, 18, 19, 20 Mortality risk is highest for patients with low fitness; risk decreases as fitness increases irrespective of sex, presence of other risk factors, or age.14, 15, 17, 19, 20, 21

Although a healthy lifestyle—including physical activity and fitness—is promoted as an essential component for prevention and management of coronary heart disease, little data are available regarding the combined health benefits of fitness and statin treatment. Furthermore, for dyslipidaemic patients who cannot take statins, whether increased mortality risk can be abated by increased fitness is unclear. We assessed the separate and combined effects of statin treatment and exercise capacity on all-cause mortality risk in veterans with dyslipidaemia.

Section snippets

Study design and patients

This prospective cohort study included patients from the Veterans Affairs Medical Centers in Washington, DC, USA and Palo Alto, CA, USA. The cohort was taken from a database of more than 20 000 veterans who had dyslipidaemia (defined by the International Classification of Diseases) and who had a symptom-limited exercise tolerance test between 1986, and 2011. The test was administered either as part of a routine assessment or to assess exercise-induced ischaemia. This information, along with the

Results

We assessed 20 023 people for eligibility. We enrolled 10 043 veterans (9700 men and 343 women). 5192 were African-American (mean age 57·8 years, SD 10·7), 4425 were white (mean age 59·5 years, SD 10·9), and 426 were other (mean age 57·6 years, SD 11). Median follow-up was 10·0 years (IQR 6·0–14·2); providing 105 334 person-years. 2318 (23·1%) patients died (no data were missing), with an average yearly mortality of 22 deaths per 1000 person-years (95% CI 13–31). Patients not treated with

Discussion

Our findings support the notion that both statin treatment and increased fitness lower mortality significantly and independently from other clinical characteristics. Our findings accord with previous reports regarding statin treatment for primary or secondary prevention of premature mortality in individuals at high risk of cardiovascular mortality.1, 2, 3, 4 Previous studies have also shown an inverse and graded association between fitness and mortality risk in apparently healthy individuals10,

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