Leg strength predicts mortality in men but not in women with peripheral arterial disease

Singh, Nimarta; Liu, Kiang; Tian, Lu; Criqui, Michael H.; Guralnik, Jack M.; Ferrucci, Luigi; Liao, Yihua; McDermott, Mary McGrae

doi:10.1016/j.jvs.2010.03.066

Cited by 48 publications

(48 citation statements)

References 16 publications

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“…However, this prior study showed no significant association of weaker isometric knee extension strength with higher cardiovascular disease mortality among men and no significant associations of weaker isometric knee extension strength with all-cause or cardiovascular disease mortality in 146 women with PAD (19). The current study identified no significant associations of knee extension isometric strength with mortality in men or women with PAD.…”

Section: Discussionmentioning

confidence: 77%

“…We previously reported that poorer isometric knee extension strength was associated with higher all-cause mortality in 264 men with PAD in the original WALCS cohort, independently of age, sex, race, comorbidities, the ABI, and other confounders (19). However, this prior study showed no significant association of weaker isometric knee extension strength with higher cardiovascular disease mortality among men and no significant associations of weaker isometric knee extension strength with all-cause or cardiovascular disease mortality in 146 women with PAD (19).…”

Section: Discussionmentioning

confidence: 98%

“…In contrast to the prior report by Singh et al (19), the current study includes data on associations of CT-measured calf muscle density, calf muscle percent fat, and calf muscle area in addition to isometric hand grip, plantar flexion strength, and knee extension power with mortality among participants with PAD. Thus, the current report includes substantially new data as compared to previously reported measures of muscle and mortality among participants with PAD.…”

Section: Discussionmentioning

confidence: 99%

“…In our WALCS cohort, we identified gender differences in associations of isometric knee extension strength with functional decline and mortality among participants with PAD (19,20). Therefore, we first assessed associations of each calf muscle characteristic and strength measure with mortality separately among men and women.…”

Section: Methodsmentioning

confidence: 99%

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Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease

McDermott

Liu

Tian

et al. 2012

Journal of the American College of Cardiology

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112

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OBJECTIVE We studied whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with PAD. BACKGROUND Men and women with lower extremity peripheral arterial disease (PAD) have lower calf muscle density and reduced lower extremity strength compared to individuals without PAD. METHODS At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power, and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed annually for up to four years. Results are adjusted for age, sex, race, body mass index, the ankle brachial index (ABI), smoking, physical activity, and comorbidities. RESULTS Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. 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), 2nd tertile-HR=0.91 (95% CI-0.51-1.62); highest density tertile (HR=1.00), P trend=0.020) and higher cardiovascular disease mortality (lowest density tertile-HR=2.39 (95% CI-0.90-6.30), 2nd tertile-HR=0.85 (95% CI-0.27-2.71); highest density tertile (HR=1.00), P trend=0.047). Poorer plantar flexion strength (P trend=0.004), lower baseline leg power (P trend=0.046), and poorer handgrip (P trend=0.005) were associated with higher all-cause mortality. CONCLUSION These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip are associated with increased mortality in participants with PAD, independently of the ABI and other confounders.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease

McDermott

Liu

Tian

et al. 2012

Journal of the American College of Cardiology

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112

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“…131 Overall leg strength has also been shown to associate with mortality in men, but not women, with PAD. 132 Taken together, these findings suggest that the morphological changes in calf muscle predispose to significant functional decline and may be an additional marker for increased risk among patients with symptomatic PAD.…”

Section: Skeletal Muscle Structural Abnormalitiesmentioning

confidence: 70%

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Hiatt¹,

Armstrong²,

Larson³

et al. 2015

Circulation Research

137

118

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P eripheral artery disease (PAD) is initiated by atherogenic mechanisms common to all major vascular territories but encompasses several distinctly important clinical sequelae.1 The global burden of PAD is large and rising, with substantial morbidity and mortality found in high-, middle-, and low-income countries. 2 The atherosclerotic occlusive disease underlying PAD is associated with an exercise limitation in the majority of patients, whereas the classic symptoms of intermittent claudication, ischemic rest pain, and ischemic ulceration are less common manifestations. 3 Patients with PAD are also at increased risk of myocardial infarction, ischemic stroke, heart failure, renovascular hypertension, and vascular death reflecting the systemic atherosclerotic burden. [4][5][6] The epidemiology of Peripheral Artery Disease Compendium© 2015 American Heart Association, Inc. The diagnosis of PAD can be ascertained by simple hemodynamic measurements, in particular, the ankle-brachial index (ABI), a test performed by measuring the systolic blood pressure in each arm and the dorsalis pedis and posterior tibial arteries of each ankle. The highest of the dorsalis pedis or posterior tibial artery pressures is the numerator of the ABI specific to each leg, whereas the highest arm pressure on either side is the denominator. A ratio of <0.90 in either leg is considered hemodynamic evidence of PAD. 16 When imaged, PAD can be characterized as one or more arterial stenoses or occlusions involving the distal aorta, iliac, femoral, popliteal, or tibial arteries. 17The underlying mechanisms responsible for the functional limitations in PAD are hemodynamic in origin, which affects the supply of oxygen and substrates to metabolically active tissue: skeletal muscle in the case of intermittent claudication and skin and subcutaneous tissues in the case of critical leg ischemia. However, additional pathophysiologic mechanisms contribute to the limb manifestations, where a reduction in blood flow alone does not fully account for the exercise limitation. Recent research into the pathophysiology of this exercise limitation has identified several important sequelae resultant from the chronic hemodynamic deficit. These changes affecting the vasculature and skeletal muscle distal to the primary hemodynamic lesions likely contribute to the mechanisms of exercise limitation in PAD. These advances are reviewed here with an additional focus on identifying possible future therapeutic strategies. Symptomatic Manifestations and Exercise Limitations in PADIn the coronary circulation, plaque rupture leading to acute ischemic events is a common clinical presentation; in PAD, progressive atherosclerosis leading to chronic stenosis and occlusion, often in series, in the arteries supplying the lower extremities dominates the symptomatic manifestations.6 Limb SymptomsPatients with PAD may present with a range of limb symptoms. Most patients are either asymptomatic or have atypical limb symptoms during exercise, whereas only a third have typical symptoms of c...

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Interventional‐ and amputation‐stage muscle proteomes in the chronically threatened ischemic limb

Ryan

Kim

Scali

et al. 2022

Clinical & Translational Med

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Background Despite improved surgical approaches for chronic limb‐threatening ischemia (CLTI), amputation rates remain high and contributing tissue‐level factors remain unknown. The purpose of this study was twofold: (1) to identify differences between the healthy adult and CLTI limb muscle proteome, and (2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation. Methods and results Gastrocnemius muscle was collected from non‐ischemic controls (n = 19) and either pre‐interventional surgery (n = 10) or at amputation outcome (n = 29) CLTI patients. All samples were subjected to isobaric tandem‐mass‐tag‐assisted proteomics. The mitochondrion was the primary classification of downregulated proteins (> 70%) in CLTI limb muscles and paralleled robust functional mitochondrial impairment. Upregulated proteins (> 38%) were largely from the extracellular matrix. Across the two independent sites, 39 proteins were downregulated and 12 upregulated uniformly. Pre‐interventional CLTI muscles revealed a robust upregulation of mitochondrial proteins but modest functional impairments in fatty acid oxidation as compared with controls. Comparison of pre‐intervention and amputation CLTI limb muscles revealed mitochondrial proteome and functional deficits similar to that between amputation and non‐ischemic controls. Interestingly, these observed changes occurred despite 62% of the amputation CLTI patients having undergone a prior surgical intervention. Conclusions The CLTI proteome supports failing mitochondria as a phenotype that is unique to amputation outcomes. The signature of pre‐intervention CLTI muscle reveals stable mitochondrial protein abundance that is insufficient to uniformly prevent functional impairments. Taken together, these findings support the need for future longitudinal investigations aimed to determine whether mitochondrial failure is causally involved in amputation outcomes from CLTI.

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Leg strength predicts mortality in men but not in women with peripheral arterial disease

Cited by 48 publications

References 16 publications

Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease

Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Interventional‐ and amputation‐stage muscle proteomes in the chronically threatened ischemic limb

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