Dataset Information

Microvascular Disease, Peripheral Artery Disease, and Amputation.

ABSTRACT:

Background

The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.

Methods

Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014. We excluded participants with known prior lower limb amputation. Using time-updated Cox proportional hazards regression, we analyzed the effect of prevalent microvascular disease (retinopathy, neuropathy, and nephropathy) and peripheral artery disease status on the risk of incident amputation events after adjusting for demographics and cardiovascular risk factors.

Results

Among 125 674 veterans without evidence of prior amputation at baseline, the rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years, yielding a total of 1185 amputations. In time-updated multivariable-adjusted analyses, compared with those without peripheral artery disease or microvascular disease, microvascular disease alone was associated with a 3.7-fold (95% CI, 3.0-4.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3-17.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3-28.1) increased risk of amputation.

Conclusions

Independent of traditional risk factors, the presence of microvascular disease increases the risk of amputation alone and synergistically increases risk in patients with peripheral artery disease. Further research is needed to understand the mechanisms by which this occurs.

SUBMITTER: Beckman JA

PROVIDER: S-EPMC6682431 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Microvascular Disease, Peripheral Artery Disease, and Amputation.

Beckman Joshua A JA Duncan Meredith S MS Damrauer Scott M SM Wells Quinn S QS Barnett Joey V JV Wasserman David H DH Bedimo Roger J RJ Butt Adeel A AA Marconi Vincent C VC Sico Jason J JJ Tindle Hilary A HA Bonaca Marc P MP Aday Aaron W AW Freiberg Matthew S MS

Circulation 20190708 6

<h4>Background</h4>The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.<h4>Methods</h4>Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through Dec ...[more]

PMID: 31280589

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Project description:BACKGROUND:Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. METHODS:Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS:In 155?647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. CONCLUSIONS:Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

Project description:BackgroundConflicting data exist regarding changes in amputation rates in patients with ulcers because of diabetes mellitus (DM) and peripheral artery disease (PAD). This study focuses on how population-based amputation rates are changing in the current treatment era.MethodsUsing the California Office of Statewide Health Planning and Development Patient Discharge database, all patients who underwent major nontraumatic lower extremity (LE) amputation in 2005 through 2011 were identified. Age-adjusted population-based amputation risk was determined by year. Gender and age trends in amputation risk were estimated separately for diabetes-related amputations and PAD-related amputations, treating all California residents as the population at risk.ResultsFrom 2005 to 2011, 32,025 qualifying amputations were performed in California. Of these, 11,896 were DM-associated (n = 1,095), PAD-associated (n = 4,335), or associated with both conditions (n = 6,466). PAD-associated amputation rates and combined PAD/DM-associated amputation rates have changed little since 2009 after decreasing substantially over the prior 5 years, but DM-associated amputation rates have continuously increased since 2005. California residents older than the age of 80 years had the most dramatic decrease in PAD-associated amputation rates from 2005 to 2011 (i.e., from 317 to 175 per million Californians). Men with PAD/DM had amputation rate 1.5 times higher than those of patients with PAD alone and 5 times higher than rates of DM patients. In women the difference between patient with PAD and PAD/DM was not seen; however, these rates were 2.5 times higher than patients with DM alone.ConclusionsPreventable amputations associated with high-risk diseases are no longer decreasing despite continuing advances in care and education. Octogenarians with PAD represent the highest risk group for amputation, but DM-associated amputations have increased since 2005. Further research to understand treatment pathways for patient with LE wounds may shed light on pathways for amputation prevention in the future.

Project description:Background Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). Methods and Results The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer rate constant, a measure of vascular leakiness; the interstitial permeability to fluid flow which reflects the permeability of the microvasculature; porosity, a measure of the fraction of the extracellular space; the outflow filtration coefficient; and the microvascular pressure with known markers of patients with PAD. Transfer rate constant, interstitial permeability to fluid flow, and microvascular pressure were higher, whereas porosity and outflow filtration coefficient were lower in patients with PAD than those in matched controls (all P values ≤0.014). In pooled analyses of all participants, the model parameters (transfer rate constant, interstitial permeability to fluid flow, porosity, outflow filtration coefficient, microvascular pressure) were significantly associated with the resting and exercise ankle-brachial indexes, claudication onset time, and peak walking time (all P values ≤0.013). Among patients with PAD, interstitial permeability to fluid flow, and microvascular pressure were higher, while porosity and outflow filtration coefficient were lower in treadmill noncompleters compared with treadmill completers (all P values ≤0.001). Conclusions Computational microvascular model parameters differed significantly between patients with PAD and matched controls. Thus, computational microvascular modeling could be of interest in studying lower extremity ischemia.

Project description:ObjectivePeripheral artery disease (PAD) is an increasing health concern with rising incidence globally. Previous studies have shown an association between PAD incidence and depression. The objective of the study was to determine the association of comorbid depression with PAD outcomes (amputation and all-cause mortality rates) in veterans.MethodsAn observational retrospective cohort of 155,647 patients with incident PAD (2003-2014) from nationwide U.S. Veterans Health Administration hospitals was conducted using the national Veterans Affairs Corporate Data Warehouse. Depression was measured using concurrent International Classification of Diseases, Ninth Revision diagnosis codes 6 months before or after PAD diagnosis. The main outcomes were incident major amputation and all-cause mortality. Crude associations were assessed with Kaplan-Meier plots. The effects of depression adjusted for covariates were analyzed using Cox proportional hazards models.ResultsDepression was present in 16% of the cohort, with the occurrence of 9517 amputations and 63,287 deaths (median follow-up, 5.9 years). Unadjusted hazard ratios (HRs) of comorbid depression for amputations and all-cause mortality were 1.32 (95% confidence interval [CI], 1.25-1.39) and 1.02 (95% CI, 0.99-1.04), respectively. After adjustment for covariates in Cox regression models, a diagnosis of comorbid depression at the time of PAD diagnosis was associated with a 13% higher amputation (HR, 1.13; 95% CI, 1.07-1.19) and 17% higher mortality (HR, 1.17; 95% CI, 1.14-1.20) risk compared with patients with no depression. On stratification by use of antidepressants, depressed patients not taking antidepressants had a 42% higher risk of amputation (HR, 1.42; 95% CI, 1.27-1.58) compared with those without depression. Patients taking antidepressants for depression still had increased risk of amputation but only 10% higher compared with those without depression (HR, 1.10; 95% CI, 1.03-1.17). Interestingly, patients taking antidepressants for other indications also had a higher risk of amputation compared with those not having depression or not taking antidepressants (HR, 1.08; 95% CI, 1.03-1.14). Having any diagnosis of depression or the need for antidepressants increased the mortality risk by 18% to 25% in the PAD cohort compared with those without depression and not taking antidepressants for any other indication.ConclusionsPAD patients with comorbid depression have a significantly higher risk of amputation and mortality than PAD patients without depression. Furthermore, untreated depression was associated with an increased amputation risk in the PAD population, more so than depression or other mental illness being treated by antidepressants. The underlying mechanisms for causality, if any, remain to be determined. The association of antidepressant treatment use with amputation risk should prompt further investigations into possible mechanistic links between untreated depression and vascular dysfunction.

Project description:BackgroundSocioeconomic factors have been shown to be associated with amputation in peripheral artery disease (PAD); however, analyses have normally focused on insurance status, race, or median income. We sought to determine whether community-level socioeconomic distress was associated with major amputation and if that association differed by race.Materials and methodsCommunity-level socioeconomic distress was measured using the distressed communities index (DCI). The DCI is a zip code level compositive socioeconomic score (0-100) that accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. A distressed community was defined as a zip code with DCI of 40 or greater. We calculated one-year risk of major amputation by DCI score for individuals with peripheral artery disease in South Carolina, 2012-2017. Treating death as competing event, we reported Fine and Gray subdistribution hazards ratios (sdHR), adjusted for patient demographic and clinical comorbidities associated with amputation. Further analyses were completed to identify potential differences in outcomes within strata of race and DCI.ResultsAmong 82,848 individuals with peripheral artery disease, the one-year incidence of amputation was 3.5% (95% CI: 3.3%, 3.6%) and was significantly greater in distressed communities than non-distressed communities (3.9%; 95% CI: 3.8%, 4.1% vs. 2.4%; 95% CI: 2.2%, 2.6%). After controlling for death and adjusting for covariates, we found an increased hazard of amputation among individuals in a distressed community (sdHR: 1.25; 95% CI: 1.14, 1.37), which persisted across racial strata. However, regardless of DCI score, Black individuals had the highest incidence of amputation.ConclusionSocioeconomic status is independently predictive of limb amputation after controlling for demographic characteristics and clinical comorbidities. Race continues to be an important risk factor, with Black individuals having higher incidence of amputation, even in non-distressed communities, than White individuals had in distressed communities.

Dataset Information

Microvascular Disease, Peripheral Artery Disease, and Amputation.

Background

Methods

Results

Conclusions

Publications

Microvascular Disease, Peripheral Artery Disease, and Amputation.

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