Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease: A Longitudinal Study

Study Questions:

Is calf muscle density and reduced lower extremity strength associated with higher mortality rates among patients with peripheral arterial disease (PAD)?


Participants were enrolled in the Walking and Leg Circulation Study II, a prospective, observational study of PAD patients. All participants underwent computed tomography measurement of calf muscle density. Measurements of lower extremity strength included knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures. Of the 434 subjects included in the study, 391 had knee extension power measured, 319 had isometric knee extension measured, 330 had isometric plantar flexion measured, and 329 had isometric hand grip measured at baseline. Participants were followed up annually for up to 4 years. Additional variables collected included age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities.


A total of 434 subjects with PAD were included in this study, of which 103 subjects (62 men and 41 women) died during a mean follow-up of 47.6 months. Women with PAD included a higher proportion of African Americans and lower proportions of participants with diabetes, angina, and heart failure compared with men with PAD. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.07-3.03; second tertile HR 0.91, 95% CI 0.51-1.62; highest density tertile HR 1.00; p trend = 0.020). A similar pattern was observed for higher cardiovascular disease mortality (lowest density tertile HR 2.39, 95% CI 0.90-6.30; second tertile HR 0.85, 95% CI 0.27-2.71; highest density tertile HR 1.00; p trend = 0.047). Measures of lower extremity strength were also associated with all-cause mortality including reduced plantar flexion strength (p trend = 0.004), lower baseline leg power (p trend = 0.046), and reduced handgrip (p trend = 0.005).


The investigators concluded that lower calf muscle density and lower extremity weakness is associated with increased mortality among men and women with PAD. These associations were independent of ankle-brachial index and potential confounders.


These data support the association between PAD, functional disability, and mortality. It is likely that exercise in PAD patients would improve function; however, it remains less clear whether improved function would reduce risk of mortality. Continued follow-up of this cohort with repeat measures would be of interest.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Vascular Medicine, Acute Heart Failure, Exercise

Keywords: Muscle, Skeletal, Ankle Brachial Index, Knee Joint, Comorbidity, Peripheral Arterial Disease, Lower Extremity, Peripheral Vascular Diseases, Walking, Tomography, Heart Failure, Disclosure, Confidence Intervals, Diabetes Mellitus

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