Risk of peripheral artery disease according to race and sex: The Atherosclerosis Risk in Communities (ARIC) study

doi:10.1016/j.atherosclerosis.2021.03.031

Atherosclerosis

Volume 324, May 2021, Pages 52-57

https://doi.org/10.1016/j.atherosclerosis.2021.03.031 Get rights and content

Highlights

•
Males have a higher risk of incident clinical peripheral artery disease (PAD) than females in Whites, but not in Blacks.
•
The risk of incident CLI differs significantly by race more than sex.
•
The elevated risk of incident critical limb ischemia (CLI) was similar between Black males and females.
•
There are both sex- and race-specific patterns of PAD.

Abstract

Background and aims

Previous community-based studies have demonstrated sex and race-based disparities in the risk of cardiovascular disease. We sought to examine the association of sex and race with incident peripheral artery disease (PAD-) and critical limb ischemia (CLI-) related hospitalizations.

Methods

In 13,451 Black and White ARIC participants without prevalent PAD at baseline (1987–89), we estimated the cumulative incidence of PAD- and CLI-related hospitalization over a median follow-up of 26 years. We quantified hazard ratios (HRs) using Cox models across four sex- and race-groups. PAD and CLI were defined by hospitalization discharge codes.

Results

The cumulative incidence of PAD-related hospitalization was higher in males than females in Whites (5.1% vs. 2.7%; p<0.001) but not in Blacks (5.7% vs. 5.0%; p=0.39). The cumulative incidence of CLI-related hospitalization differed significantly by race more than sex, occurring in 3.1% Black males, 3.1% Black females, 1.4% White males, and 0.8% White females (p<0.001). After risk factor adjustment, the risk of incident PAD-related hospitalization was similar for White males vs. White females [HR 1.14, 95%CI 0.90–1.45], and slightly higher for Black males [HR 1.26, 95%CI 0.92–1.72] and Black females [HR 1.39, 95%CI 1.03–1.87] compared to White females. The adjusted risk of incident CLI-related hospitalization was similar for White males vs. White females [HR 1.15, 95%CI 0.75–1.76], and significantly higher for Black males [HR 1.96, 95%CI 1.22–3.16] and Black females [HR 2.06, 95%CI 1.31–3.24] compared to White females.

Conclusions

These data suggest that there are both sex- and race-specific patterns of PAD-related hospitalization that lead to differences in clinical disease risk and presentation.

Graphical abstract

Introduction

Women have a lower cumulative lifetime risk of atherosclerotic cardiovascular disease than men [[1], [2], [3]]. However, several epidemiologic studies based on ankle-brachial index (ABI) have demonstrated a similar or higher prevalence of peripheral artery disease (PAD) in women compared to men [[4], [5], [6]]. Although the higher prevalence in women may be partially due to lower ABI in persons with shorter height [7], women also tend to have more advanced disease upon presentation with PAD than men [8]. To our knowledge, there are no prospective studies that have evaluated the association of sex with incident PAD, including its severe form, critical limb ischemia (CLI).

There have also been a number of studies describing racial disparities in PAD. In a recent meta-analysis comparing PAD prevalence in different ethnic groups, Blacks were found to have the highest prevalence of disease, followed by Whites and south Asians, respectively [9]. Black patients have been shown to have a higher likelihood of lower extremity amputation compared to White patients [10,11], suggesting a higher prevalence of CLI in Blacks.

The aim of this study was to quantify the risk of PAD- and CLI-related hospitalizations according to sex and race using data from the Atherosclerosis Risk in Communities (ARIC) Study. We hypothesize that incident PAD- and CLI-related hospitalizations will be similar between men and women, and higher in Black participants compared to White participants.

Section snippets

Study cohort

The ARIC Study is a prospective community-based cohort study that enrolled 15,792 adults between 1987 and 1989 from four U.S. communities, including Washington County, Maryland, suburban Minneapolis, Minnesota, Jackson, Mississippi, and Forsyth County, North Carolina. Participants were between 45 and 64 years of age at baseline, and have been followed with serial in-person assessments and hospitalization surveillance. For this analysis, we excluded participants with races other than Black or

Baseline characteristics

Among the 13,451 ARIC participants analyzed, 45.7% (N = 6143) were male and 24.0% (N = 3221) were Black. Within the White cohort, 48.1% (N = 4920) were male. Within the Black cohort, 38.0% (N = 1223) were male. Participant socioeconomic factors, comorbidities, blood pressure, and plasma cholesterol levels differed across sex-race categories (Table 1). In both the White and Black race groups, females tended to have a higher prevalence of anti-hypertensive use and heart failure but a lower

Discussion

Based on 26 years of follow-up in Black and White participants in the ARIC study, we found that the crude cumulative incidence of PAD-related hospitalization was higher for males than females in Whites but not in Blacks. The crude cumulative incidence of CLI was largely similar for males and females within race groups. After adjusting for covariates, Blacks had the highest risk of incident CLI-related hospitalization regardless of sex. The elevated risk of PAD and CLI in White males compared to

Financial support

The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Dr. Hicks was supported by NIH/NIDDK grant K23DK124515. Dr. Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Dr. Matsushita was supported

Author contributions

CWH, ND, LK, and KM designed and conceptualized study and analyzed the data. CWH, ND, LK, SB, CAK, ARF, GH, JC, JHB, ES, and KM interpreted the data. CWH, ND, and KM drafted the manuscript for intellectual content. LK, SB, CAK, ARF, GH, JC, JHB, and ES revised the manuscript for intellectual content.

CRediT authorship contribution statement

Caitlin W. Hicks: Conceptualization, Formal analysis, designed and conceptualized study and analyzed the data, interpreted the data, Writing – original draft, drafted the manuscript for intellectual content. Ning Ding: Conceptualization, Formal analysis, designed and conceptualized study and analyzed the data, interpreted the data, Writing – original draft, drafted the manuscript for intellectual content. Lucia Kwak: Conceptualization, Formal analysis, designed and conceptualized study and

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank the staff and participants of the ARIC study for their important contributions.

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Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce.
We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts.
Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined.
In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y.
This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.
Implementing methods in the ELEGANCE registry to increase diversity in clinical research
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Women and underrepresented minorities (URMs) who are at an increased risk of presenting with severe peripheral artery disease (PAD) and have different responses to treatment compared with non-Hispanic White males yet are underrepresented in PAD research.
ELEGANCE is a global, prospective, multi-center, post-market registry of PAD patients treated with drug-eluting device that aims to enroll at least 40% women and 40% URMs. The study design incorporates strategies to increase enrollment of women and URMs. Inclusion criteria are age ≥18 years and treatment with any commercially available Boston Scientific Corporation drug-eluting device marketed for peripheral vasculature lesions; exclusion criterion is life expectancy <1 year.
Of 750 patients currently enrolled (951 lesions) across 39 sites, 324 (43.2%) are female and 350 (47.3%) are URMs (21.6% Black, 11.2% Asian, 8.5% Hispanic/Latino, and 5.3% other). Rutherford classification is distributed differently between sexes (P = .019). Treatment indication differs among race/ethnicity groups (P = .003). Chronic limb-threatening ischemia was higher for Black (38.3%) and Hispanic/Latino (28.1%) patients compared with non-Hispanic White (21.8%) and Asian patients (21.4%). De-novo stenosis was higher in Asian patients (92.3%) compared with Black, non-Hispanic White, and Hispanic/Latino patients (72.2%, 68.7%, and 77.8%, respectively; P < .001). Mean lesion length was longest for Black patients (162.7 mm), then non-Hispanic White (135.2 mm), Asian (134.8 mm), and Hispanic/Latino patients (128.1 mm; P = .008).
Analyses of data from the ELEGANCE registry show that differences exist in baseline disease characteristics by sex and race/ethnicity; these may be the result of other underlying factors, including time to diagnosis, burden of undermanaged comorbidities, and access to care.
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Cancers and cardiovascular diseases are the top two causes of death in the United States. Over the past decades, novel therapies have slowed the cancer mortality rate, yet cardiac failures have risen due to the toxicity of cancer treatments. The mechanisms behind this relationship are poorly understood and it is crucial that we properly treat patients at risk of developing cardiac failure in response to cancer treatments. Currently, we rely on early-stage biomarkers of inflammation and angiogenesis to detect cardiotoxicity before it becomes irreversible. Identification of such biomarkers allows healthcare professionals to decrease the adverse effects of cancer therapies. Angiogenesis and inflammation have a systemic influence on the heart and vasculature following cancer therapy. In the field of cardio-oncology, there has been a recent emphasis on gender and racial disparities in cardiotoxicity and the impact of these disparities on disease outcomes, but there is a scarcity of data on how cardiotoxicity varies across diverse populations. Here, we will discuss how current markers of angiogenesis and inflammation induced by cancer therapy are related to disparities in cardiovascular health.
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We used the Vascular Quality Initiative database, linked with Medicare claims data, to identify patients who underwent initial femoropopliteal PVI between 2017 and 2018. DCI scores were assigned using patient-level zip code data. The primary outcomes were 24-month mortality and major amputation. We used time-dependent receiver operating characteristic curve analysis to determine an optimal DCI value to stratify patients into risk categories for 24-month mortality and major amputation. Mixed Cox regression models were constructed to estimate the association of DCI with 24-month mortality and major amputation.
The final cohort consisted of 16,864 patients, of whom 4734 (28.1%) were classified as having high community distress (DCI ≥70). At 24 months, mortality was elevated in patients with high community distress (30.7% vs 29.5%, P = .02), as was major amputation (17.2% vs 13.1%, P <.001). After adjusting for demographic and clinical characteristics, a 10-point higher DCI score was associated with increased risk of mortality (hazard ratio: 1.01; 95% confidence interval: 1.00-1.03) and major amputation (hazard ratio: 1.02; 95% confidence interval: 1.00-1.04).
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Gender Differences in Outpatient Peripheral Artery Disease Management in Germany: A Population Based Study 2009–2018
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Citation Excerpt :
Such therapies are consistently recommended by all major societies.5–7 However, despite clear guideline recommendations regarding medical treatment of patients, implementation of those guideline recommendations is inadequate and depends on social status and race.8,9 The present authors recently reported underuse of guideline recommended therapy for statutorily insured PAD patients in Germany, highlighting treatment opportunities.10
Peripheral artery disease (PAD) is a major risk factor for morbidity and death. Despite clear guideline recommendations regarding outpatient treatment and pharmacotherapy, implementation is inadequate. Gender differences are becoming increasingly important, especially in patients with atherosclerosis.
Gender stratified PAD prevalence and differences in treatment by specialised outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year in Germany between 2009 and 2018. This was based on claims data according to §295 of the social code (SGB V) and drug prescription data according to §300 SGB V. Diagnosis of PAD was defined according to ICD I70.2-9 coding. Statistical analysis was performed with the chi square test for trend and two way ANOVA.
In total, 17 633 970 patients with PAD were identified, of whom 47% were female. Prevalence of PAD in Germany increased between 2009 and 2018 and was higher in male patients. Only a minority of 37.1% presented to a vascular specialist. Interestingly, female patients were both less likely to present to a vascular specialist and to receive guideline recommended pharmacotherapy. Overall prescription rates of statins and antiplatelet drugs increased between 2009 and 2018, however. PAD stages were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). In CLTI even fewer patients received a statin, with the gender gap increasing.
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Risk of peripheral artery disease according to race and sex: The Atherosclerosis Risk in Communities (ARIC) study

Highlights

Abstract

Background and aims

Methods

Results

Conclusions

Graphical abstract

Introduction

Section snippets

Study cohort

Baseline characteristics

Discussion

Financial support

Author contributions

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgements

Am. J. Med.

J. Vasc. Surg.

J. Vasc. Surg.

Ann. Vasc. Surg.

J. Vasc. Surg.

J. Vasc. Surg.

Lancet

Lancet

Ann. Vasc. Surg.

J. Vasc. Surg.

Can. J. Cardiol.

Am. J. Prev. Med.

J. Vasc. Surg.

J. Vasc. Surg.

Gend. Med.

J. Am. Coll. Cardiol.

J. Vasc. Surg.

J. Vasc. Surg.

Sex differences in ischemic heart disease: advances, obstacles, and next steps

Circ Cardiovasc Qual Outcomes

Editor's Choice-Sex differences in young patients with acute myocardial infarction: a VIRGO study analysis

Eur Heart J Acute Cardiovasc Care

Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study

Circulation

Ankle brachial index values, leg symptoms, and functional performance among community-dwelling older men and women in the lifestyle interventions and independence for elders study

J Am Heart Assoc

Association of sex and height with a lower ankle brachial index in the general population

Vasc. Med.

Ethnic differences in the prevalence of peripheral arterial disease: a systematic review and meta-analysis

Expert Rev. Cardiovasc Ther.

Racial and ethnic differences in patterns of treatment for acute peripheral arterial disease in the United States, 1998-2006

J. Vasc. Surg.

The diagnosis of ischaemic heart pain and intermittent claudication in field surveys

Bull. World Health Organ.