Peripheral artery disease (PAD) affects more than 200 million adults worldwide. Patients with lower extremity PAD have a heightened risk for cardiovascular events because of the systemic nature of ...atherosclerosis, and benefit from treatment with risk factor-modifying therapies. Limb symptoms in PAD include intermittent claudication and diminished walking ability. Arterial obstruction from atherosclerotic lesions initiates limb ischemia; however, decreased perfusion incompletely determines the clinical expression of PAD and its response to therapy. Potential mechanistic drivers of claudication in addition to arterial obstruction include inflammation, vascular dysfunction, reduced microvascular flow, impaired angiogenesis, and altered skeletal muscle function. An improved understanding of the pathophysiology of limb symptoms has the potential to accelerate development of novel therapeutic strategies to increase functional capacity in patients with PAD.
Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal ...relationships between vascular stiffening and blood pressure elevation have not been fully delineated.
To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression.
Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 last visit: January 25, 2008) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity CFPWV, forward wave amplitude FWA, and augmentation index) were examined over a 7-year period in 1759 participants (mean SD age: 60 9 years; 974 women).
The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8.
In a multivariable-adjusted regression model, higher FWA (β, 1.3 95% CI, 0.5-2.1 mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 95% CI, 0.5-2.6 mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio OR, 1.6 95% CI, 1.3-2.0 per 1 SD; P < .001), augmentation index (OR, 1.7 95% CI, 1.4-2.0 per 1 SD; P < .001), and CFPWV (OR, 1.3 95% CI, 1.0-1.6 per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases 32% in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 95% CI, 1.04-1.46) and lower flow-mediated dilation (OR, 0.80 95% CI, 0.67-0.96) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7).
In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.
Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. Modifiable risk factors including cigarette smoking, dyslipidemia, diabetes, poor diet quality, obesity, and physical ...inactivity, along with underlying genetic factors contribute to lower extremity atherosclerosis. Patients with PAD often have coexistent coronary or cerebrovascular disease, and increased likelihood of major adverse cardiovascular events, including myocardial infarction, stroke and cardiovascular death. Patients with PAD often have reduced walking capacity and are at risk of acute and chronic critical limb ischemia leading to major adverse limb events, such as peripheral revascularization or amputation. The presence of polyvascular disease identifies the highest risk patient group for major adverse cardiovascular events, and patients with prior critical limb ischemia, prior lower extremity revascularization, or amputation have a heightened risk of major adverse limb events. Medical therapies have demonstrated efficacy in reducing the risk of major adverse cardiovascular events and major adverse limb events, and improving function in patients with PAD by modulating key disease determining pathways including inflammation, vascular dysfunction, and metabolic disturbances. Treatment with guideline-recommended therapies, including smoking cessation, lipid lowering drugs, optimal glucose control, and antithrombotic medications lowers the incidence of major adverse cardiovascular events and major adverse limb events. Exercise training and cilostazol improve walking capacity. The heterogeneity of risk profile in patients with PAD supports a personalized approach, with consideration of treatment intensification in those at high risk of adverse events. This review highlights the medical therapies currently available to improve outcomes in patients with PAD.
Peripheral artery disease is an obstructive, atherosclerotic disease of the lower extremities causing significant morbidity and mortality. Black Americans are disproportionately affected by this ...disease while they are also less likely to be diagnosed and promptly treated. The consequences of this disparity can be grim as Black Americans bear the burden of lower extremity amputation resulting from severe peripheral artery disease. The risk factors of peripheral artery disease and how they differentially affect certain groups are discussed in addition to a review of pharmacological and nonpharmacological treatment modalities. The purpose of this review is to highlight health care inequities and provide a review and resource of available recommendations for clinical management of all patients with peripheral artery disease.
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