Higher Risk Of Peripheral Arterial Disease Research Articles

Smoking as a risk factor for lower extremity peripheral artery disease in women compared to men: A systematic review and meta-analysis.

To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318). PubMed, EMBASE, and CINAHL were searched (3 March 2024) for studies reporting associations between smoking and PAD in both sexes, at least adjusted for age. Data were pooled using random effects. Between-study heterogeneity was examined using I2 statistic and Cochran's Q test. Newcastle-Ottowa Scale was adopted for quality assessment. Four cohort studies (n = 2,117,860, 54.4% women) and thirteen cross-sectional studies (n = 230,436, 59.9% women) were included. In cohort studies, former and current smokers had higher risk of PAD than never smokers. Compared to those who never or previously smoked, women current smokers (relative risk (RR) 5.30 (95% confidence interval 3.17, 8.87)) had higher excess risk of PAD than men (RR 3.30 (2.46, 4.42)), women-to-men ratio of RR 1.45 (1.30, 1.62)(I2 = 0%, p = 0.328). In cross-sectional studies, risk of PAD was higher among former and current compared to never smokers, more so in men, women-to-men ratios of odds ratio: 0.64 (0.46, 0.90)(I2 = 30%, p = 0.192), 0.63 (0.50, 0.79)(I2 = 0%, p = 0.594), respectively. For both sexes, risk of PAD was higher among current smokers compared to those who were not currently smoking. Cohort studies and five cross-sectional studies were of good quality, scoring 6 to 8 of a possible maximum 9 points. Eight cross-sectional studies scored 2 to 5. Further research is required to elucidate sex differences in the relationships between smoking and PAD, as the current evidence is limited and mixed. Tobacco-control programs should consider both sexes.

Association of prognostic nutritional index with peripheral artery disease in US adults: a cross-sectional study

BackgroundThe objective of this study was to investigate the relationship between the prognostic nutritional index (PNI) and peripheral artery disease (PAD).MethodsThe present study is a cross-sectional study based on the National Health and Nutrition Survey (1999–2004). The laboratory-calculated PNI was divided into four groups based on quartiles(Q1:PNI ≤ 50.00; Q2: 50.01–53.00; Q3:53.01–56.00; Q4: > 56.00). PAD was defined as an ankle brachial pressure index (ABPI) ≤ 0.9 on the left or right. The relationship between PNI and PAD was examined using multifactor weighted logistic regression analysis, as well as subgroup analysis. Subgroup analyses were conducted based on demographic and clinical variables.ResultsA total of 5,447 individuals were included in our final analysis. The age of the participants was 59.56 ± 13.10 years, and males accounted for 52.8% (n = 2820). The prevalence of PAD was 6.7% (n = 363). After adjusting for all factors, participants with Q1 still had an increased risk of PAD, with an OR value of 1.593 and a 95% CI of 1.232–1.991. Subgroup analysis showed no significant interaction among multiple factors.ConclusionsIn summary, we report that lower PNI are associated with a higher risk of PAD in US adults. It is hoped that this discovery can provide a reference for the prevention of PAD.

Sex differences in risk factors for incident peripheral artery disease hospitalisation or death: Cohort study of UK Biobank participants.

Women with peripheral artery disease (PAD) often have atypical symptoms, late hospital presentations, and worse prognosis. Risk factor identification and management are important. We assessed sex differences in associations of risk factors with PAD. 500,207 UK Biobank participants (54.5% women, mean age 56.5 years) without prior hospitalisation of PAD at baseline were included. Examined risk factors included blood pressure, smoking, diabetes, lipids, adiposity, history of stroke or myocardial infarction (MI), socioeconomic status, kidney function, C-reactive protein, and alcohol consumption. Poisson and Cox regressions were used to estimate sex-specific incidence of PAD hospitalisation or death, hazard ratios (HRs), and women-to-men ratios of HRs (RHR) with confidence intervals (CIs). Over a median of 12.6 years, 2658 women and 5002 men had a documented PAD. Age-adjusted incidence rates were higher in men. Most risk factors were associated with a higher risk of PAD in both sexes. Compared with men, women who were smokers or had a history of stroke or MI had a greater excess risk of PAD (relative to those who never smoked or had no history of stroke or MI): RHR 1.18 (95%CI 1.04, 1.34), 1.26 (1.02, 1.55), and 1.50 (1.25, 1.81), respectively. Higher high-density lipoprotein cholesterol (HDL-C) was more strongly associated with a lower risk of PAD in women than men, RHR 0.81 (0.68, 0.96). Compared to HDL-C at 40 to 60 mg/dL, the lowest level of HDL-C (≤40 mg/dL) was related to greater excess risk in women, RHR 1.20 (1.02, 1.41), whereas the highest level of HDL-C (>80 mg/dL) was associated with lower risk of PAD in women, but higher risk in men, RHR 0.50 (0.38, 0.65). While the incidence of PAD was higher in men, smoking and a history of stroke or MI were more strongly associated with a higher risk of PAD in women than men. HDL-C was more strongly associated with a lower risk of PAD in women than men.

Assessment and Diagnosis of Peripheral Artery Disease in Patients with Diabetes

Peripheral artery disease (PAD) is a chronic circulatory condition that occurs when the arteries that supply blood to the legs and feet are narrowed or blocked, leading to reduced blood flow to these areas. PAD is a common complication of type 2 diabetes, affecting up to 1 in 3 individuals with the condition. Assessment of PAD in individuals with diabetes typically involves a physical exam, ankle-brachial index (ABI) measurement, and imaging tests such as Doppler ultrasound or angiography. The ABI is a noninvasive measure that compares the blood pressure in the ankles and arms, with a lower ABI indicating a higher risk of PAD. Management of PAD in type 2 diabetes involves a multifaceted approach, including lifestyle modifications, medication, and revascularization procedures. Lifestyle changes such as smoking cessation and regular exercise can improve PAD symptoms and reduce the risk of disease progression. Medications such as antiplatelet agents, statins, and blood pressure-lowering drugs help to manage PAD and its associated risk factors. Revascularization procedures such as angioplasty or bypass surgery may be necessary in severe cases of PAD to restore blood flow to the affected limbs. In addition, these procedures should be considered in the feet of patients with diabetes if there is evidence of ischemia. Early detection and management of PAD in type 2 diabetes are critical to preventing complications such as non-healing wounds, infections, and amputations. Individuals with type 2 diabetes should undergo regular screening for PAD and work with their healthcare providers to develop a personalized treatment plan.

Sex as a Key Determinant of Peripheral Artery Disease: Epidemiology, Differential Outcomes, and Proposed Biological Mechanisms.

Atherosclerotic peripheral artery disease (PAD) is associated with functional limitations and an increased risk of poor cardiovascular outcomes. Although men are traditionally viewed at higher risk of PAD than women, the true prevalence and incidence is inconsistent among available reports. Some of this variability is due to differences in PAD-related symptoms among women as well as sex-based differences in diagnostic tests, such as the ankle-brachial index, and it is critical for future epidemiologic studies to account for these differences. Generally, women with PAD experience greater functional impairment and decline then men and are less likely to receive guideline-directed medical therapy. In some settings, women are also more likely to present at later stages of disease and more often undergo lower limb amputation than men. Animal data exploring the biological underpinnings of these sex differences are limited, but several mechanisms have been postulated, including differential plaque morphology, alterations in the immune response, and hormonal variation and protection. Epidemiologic data suggest a link between inflammation and PAD and also reveal sex differences in lipid profiles associated with risk of PAD. In this review, we discuss available data on sex differences in PAD with additional focus on potential biological explanations for these differences. We also emphasize important knowledge gaps in this area, including under-representation of women in PAD clinical trials, to help guide future investigations and eliminate sex disparities in PAD.

Novel cardiovascular biomarkers associated with peripheral arterial disease in men screened for abdominal aortic aneurysm.

Background: Peripheral arterial disease (PAD) is a common atherosclerotic disease with severity ranging from asymptomatic to chronic limb threatening ischemia. The aim of the present cross-sectional study was to identify novel biomarkers associated with PAD. Patients and methods: Levels of 91 cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel from a cohort consisting of 267 65-year-old men recruited from a screening program for abdominal aortic aneurysm (AAA) Levels of protein biomarkers were compared in men with and without PAD (defined as an ankle brachial index of <0.9) and their diagnostic potential was calculated by receiver-operating characteristic analysis. Results: The prevalence of PAD was 14.2% (38/267). After adjustment for multiple comparisons, levels of the following 11 biomarkers remained significantly higher (p<0.0001) in patients with PAD: secretoglobin family 3A member 2, osteoprotegerin, urokinase-type plasminogen activator surface receptor, serum macrophage chemokine ligand 16, matrix metalloproteinase 9, p-selectin, growth differentiation factor 15, elafin, cystatin B, trefoil factor 3, and fatty acid-binding protein 4. Multivariable logistic regression analysis (adjusted for smoking, use of antihypertensive and lipid-lowering medication, and metformin) showed that 11 biomarkers were significantly associated with higher risk of PAD with odds ratios ranging from 1.6 to 2.4. Area under curve calculated by receiver operating characteristic curve analysis (diagnostic value) for each protein biomarker ranged from 0.63 to 0.74. Conclusions: We have identified multiple proteins with a potential to be diagnostic biomarkers for PAD, and further research is warranted to clarify their potential predictive and prognostic value.

Triglyceride Glucose Index Was Associated With the Risk of Peripheral Artery Disease.

This study aims to investigate the relationship between the triglyceride glucose (TyG) index and peripheral artery disease (PAD). A total of 3125 participants with completed TyG and ankle brachial pressure index (ABPI) records were enrolled from the National Health and Nutrition Examination Survey (NHANES) cycle of 1999-2004. The TyG index was calculated as ln [triglycerides (mg/dL) × glucose (mg/dL)/2], and the presence of PAD was defined as ABPI ≤.9. The participants were 59.9 ± 12.9years old and 51.5% (1608) were male. The prevalence of PAD was 7.2% (225). Compared with the reference lowest quartile of TyG index, the highest quartile was associated with 1.27-fold increased (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.53-3.41; P < .001) risk of PAD. After adjusting for sociodemographic, lifestyles, and cardiometabolic factors, the multivariate-adjusted OR and 95% CI were 1.74 (1.02-3.01; P = .044) in participants within the highest quartile. Subgroup analysis showed that the association between TyG index and the risk of PAD was still consistent across subgroups. In conclusion, higher TyG index was significantly associated with the higher risk of PAD, which could be a marker of PAD.

Higher Systemic Immune-Inflammation Index is Associated With Higher Likelihood of Peripheral Arterial Disease

To explore the association between SII (Systemic Immune-Inflammation Index) and PAD (peripheral arterial disease) in American adults. Related data from NHANES (National Health and Nutrition Examination Survey) database (1999-2004) were collected and analyzed. PAD was diagnosed by ankle brachial index assessment. The association between SII and prevalent PAD was assessed using multivariable logistic regression. A total of 6,576 eligible subjects (including 6117 subjects without PAD and 459 with PAD) were finally enrolled in the study, among which there were 3,187 females and 3,389 males with a mean SII of 585.3 ± 401.5. The age of the subjects with PAD was larger compared to those without PAD (70.2 ± 11.8 vs. 58.7 ± 12.5), and the incidence of chronic diseases, that's CAD, diabetes and hypertension, was higher in those without PAD (P < 0.001). Multivariable logistic regression indicated that a high SII level was an independent risk factor for PAD (OR=1.51, 95% CI: 1.18- 1.93, P=0.0012) after adjusting for body mass index, race, sex, age, diabetes mellitus (yes/no), hypertension (yes/no), and cardiovascular disease (yes/no). It is suggested that a higher SII is associated with a higher risk of PAD.

Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohort-based study.

The atherogenic potential of cholesterol in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged. Elevated remnant cholesterol is associated with increased risk of myocardial infarction and ischaemic stroke. We tested the hypothesis that elevated remnant cholesterol is also associated with increased risk of peripheral artery disease (PAD). We studied 106 937 individuals from the Copenhagen General Population Study recruited in 2003-15. During up to 15 years of follow-up, 1586 were diagnosed with PAD, 2570 with myocardial infarction, and 2762 with ischaemic stroke. We also studied 13 974 individuals from the Copenhagen City Heart Study recruited in 1976-78. During up to 43 years of follow-up, 1033 were diagnosed with PAD, 2236 with myocardial infarction, and 1976 with ischaemic stroke. Remnant cholesterol was calculated from a standard lipid profile. Diagnoses were from Danish nationwide health registries. In the Copenhagen General Population Study, elevated remnant cholesterol levels were associated with higher risk of PAD, up to a multivariable adjusted hazard ratio (HR) of 4.8 (95% confidence interval 3.1-7.5) for individuals with levels ≥1.5 mmol/L (58 mg/dL) vs. <0.5 mmol/L (19 mg/dL). Corresponding results were 4.2 (2.9-6.1) for myocardial infarction and 1.8 (1.4-2.5) for ischaemic stroke. In the Copenhagen City Heart Study, corresponding HRs were 4.9 (2.9-8.5) for PAD, 2.6 (1.8-3.8) for myocardial infarction, and 2.1 (1.5-3.1) for ischaemic stroke. Elevated remnant cholesterol is associated with a five-fold increased risk of PAD in the general population, higher than for myocardial infarction and ischaemic stroke.

Associations of cardiac injury biomarkers with risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis

IntroductionWe investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle–brachial index (ABI). MethodsHs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively. ResultsOverall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes. ConclusionsNT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

Triglyceride-glucose index in the development of peripheral artery disease: findings from the Atherosclerosis Risk in Communities (ARIC) Study

BackgroundIt remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).MethodsWe included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987–1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.ResultsOver a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049–1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028–1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132–1.740) and 1.742 (1.294–2.344), respectively] after multivariate adjustments for traditional PAD risk factors.ConclusionsHigher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.Trial registration: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.

Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry

IntroductionPatients with diabetes have increased risk of lower limb revascularization and amputation due to higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The additive effect of coronary artery...

Association between Cystatin C and Peripheral Artery Disease in the Chinese Han Population

Recent studies of the association between cystatin C and peripheral artery disease (PAD) have produced inconsistent results, and few studies have been conducted to investigate this association in the Chinese Han population. Therefore, we evaluated the relationship between cystatin C and PAD using Chinese data. We performed a secondary analysis of the data from a previously published case-control study about PAD in our center. We examined the relationship between cystatin C and PAD by logistic regression models and subgroup and interaction analyses. We also constructed a propensity score-matched population by matching the conventional risk factors to further validate this association. In addition, we explored the relationship between cystatin C level and ankle-brachial index (ABI) strata (<0.4, ≥0.4) to shed light on a possible dose-dependent relationship between cystatin C levels and PAD severity. In total, 426 participants were included for evaluation. The mean serum cystatin C concentration was significantly lower in the control group than that in the case group (1.06±0.19mg/L vs. 1.24±0.34mg/L, P<0.001). After adjustment for conventional risk factors, the risk of PAD was significantly higher in individuals with a cystatin C level of ≥1.25mg/L. A 17% higher risk of PAD was associated with each 100-μg/L increase in the serum cystatin C level. Similar results were seen in the analyses of the propensity score-matched population comprising 164 participants. Furthermore, patients with an ABI <0.4 had higher cystatin C level than those with an ABI ≥0.4 (1.31±0.05mg/L vs. 1.18±0.03mg/L, P=0.03). Our analysis indicated that an elevated cystatin C level is significantly associated with an increased risk of PAD in the Chinese Han population. Larger Chinese prospective cohort studies are needed to validate these findings.

Abstract 15999: Machine Learning to Identify Patients at High Risk for Peripheral Arterial Disease From Electronic Health Record Data

Introduction: Peripheral arterial disease (PAD) is a common and underdiagnosed disease associated with significant morbidity and increased risk of major adverse cardiovascular events. Targeted screening of individuals at high risk for PAD could facilitate early diagnosis and allow for prompt initiation of interventions aimed at reducing cardiovascular and limb events. However, no widely accepted PAD risk stratification tools exist. Hypothesis: We hypothesized that machine learning algorithms can identify patients at high risk for PAD, defined by ankle-brachial index (ABI) &lt;0.9, from electronic health record (EHR) data. Methods: Using data from the Vanderbilt University Medical Center EHR, ABIs were extracted for 8,093 patients not previously diagnosed with PAD at the time of initial testing. A total of 76 patient characteristics, including demographics, vital signs, lab values, diagnoses, and medications were analyzed using both a random forest and least absolute shrinkage and selection operator (LASSO) regression to identify features most predictive of ABI &lt;0.9. The most significant features were used to build a logistic regression based predictor that was validated in a separate group of individuals with ABI data. Results: The machine learning models identified several features independently correlated with PAD (age, BMI, SBP, DBP, pulse pressure, anti-hypertensive medication, diabetes medication, smoking, and statin use). The test statistic produced by the logistic regression model was correlated with PAD status in our validation set. At a chosen threshold, the specificity was 0.92 and the positive predictive value was 0.73 in this high-risk population. Conclusions: Machine learning can be applied to build unbiased models that identify individuals at risk for PAD using easily accessible information from the EHR. This model can be implemented either through a high-risk flag within the medical record or an online calculator available to clinicians.

Association between nontraditional lipid profiles and peripheral arterial disease in Chinese adults with hypertension

BackgroundData on the relationship between nontraditional lipid profiles [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C)] and the risk of peripheral artery disease (PAD) are limited. The present study investigated the relationship of nontraditional lipid indices with PAD in hypertensive patients.MethodsThis cross-sectional study was performed among 10,900 adults with hypertension. Participants were diagnosed with PAD when their ankle-brachial index (ABI) was < 0.9. The association between nontraditional lipid profiles and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline.ResultsAll nontraditional lipid indices were independently and positively associated with PAD in a dose-response fashion. After multivariable adjustment, the per SD increments of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C were all significantly associated with 37, 14, 40, and 24% higher risk for PAD, respectively. The adjusted ORs (95% CI) for PAD were 1.77 (1.31, 2.40), 1.71 (1.25, 2.34), 2.03 (1.50, 2.74), and 1.70 (1.25, 2.31) when comparing the highest tertile to the lowest tertile of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C, respectively.ConclusionsAmong Chinese hypertensive adults, all nontraditional lipid indices were positively associated with PAD, and the LDL-C/HDL-C and TC/HDL-C ratios were better than the other nontraditional lipid indices for predicting PAD. These findings may improve the risk stratification of cardiovascular disease and dyslipidemia management.Trial registrationCHiCTR, ChiCTR1800017274. Registered 20 July 2018.

The Association of Blood Glucose and Diabetes with Abdominal Aortic Aneurysm, Carotid Stenosis and Peripheral Arterial Disease: An Observational Study of 630,000 Patients Attending Vascular Screening

Introduction - Diabetes is an important risk factor for atherosclerotic vascular disease, and previous studies have also shown a positive continuous association between blood glucose concentrations throughout the “normal” reference range and cardiovascular disease. However, diabetes appears to be inversely associated with abdominal aortic aneurysm (AAA). This study reports associations between blood glucose concentration and diabetes with AAA, carotid stenosis and peripheral arterial disease (PAD). Methods - Between 2008 and 2013, 3.3 million self-referred individuals attended cardiovascular screening clinics (Life Line Screening) in the US and UK. Assessments included an aortic ultrasound scan, a carotid duplex, and ankle-brachial pressure index (ABPI). Major cardiovascular risk factors and medical history were recorded, and approximately one fifth of participants also underwent blood glucose assays. Diabetes was defined according to previous diagnosis or treatment. Participants with incomplete data or prior cardiovascular disease were excluded, yielding 628 246 individuals in the current report. Results - The mean age at screening was 63 ± 10 years, and 64% of attendees were women. The following prevalences were observed: AAA (infra-renal aorta ≥ 30mm) = 0.5%; carotid artery stenosis (peak systolic velocity generally ≥110cm/s) = 3.5%; PAD (ABPI <0.9) = 2.6%. A prior diagnosis of diabetes was associated with higher risk of PAD (OR, 95%CI: 1.77, 1.71-1.84) and carotid stenosis (1.71, 1.66-1.76), and among participants without a prior diagnosis of diabetes the prevalence of carotid stenosis and PAD increased with higher blood glucose levels across the normal reference range. For AAA, a prior diagnosis of diabetes was associated with a significantly lower risk (0.83 0.77-0.90), however among attendees without diabetes, the prevalence of AAA increased with higher blood glucose levels across the normal reference range. Conclusion - Across the normal reference range, higher blood glucose concentrations are associated with increased risk of carotid stenosis, PAD and AAA, but a diagnosis of diabetes was associated with a lower risk of AAA. This raises the possibility that the “protection” conferred by diabetes against AAA could be due to a treatment effect, but this hypothesis needs to be tested in randomised trials.

2017 ACC/AHA blood pressure classification and incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study.

The aim of this study was to evaluate the associations of blood pressure categorization based on the 2017 American College of Cardiology and American Heart Association guideline with the risk of peripheral artery disease (PAD). Among 13,113 middle-aged participants, we investigated the associations of 2017 blood pressure categories (systolic <120 and diastolic <80 mmHg (normal if no anti-hypertensive medications; reference), 120-129 and <80 (elevated), 130-139 and/or 80-89 (stage 1 hypertension), and ≥140 and/or ≥90 (stage 2 hypertension)) with incident PAD (hospitalizations with a diagnosis or leg revascularization) using Cox regression models. Analyses were separately conducted in individuals with and without anti-hypertensive medications. During a median follow-up of 25.4 years, 466 incident PAD occurred (271 cases in 9858 participants without anti-hypertensive medications). In participants without anti-hypertensive medications, we observed significant hazard ratios of PAD in elevated blood pressure (1.80 (1.28-2.51)) and stage 2 hypertension (2.40 (1.72-3.34)), but not in stage 1 hypertension. Analyzing systolic and diastolic blood pressure separately, higher systolic blood pressure categories showed significant associations with incident PAD in a graded fashion whereas, for diastolic blood pressure, only ≥90 mmHg did. Generally similar patterns were seen among participants on anti-hypertensive medication, while they had higher risk of PAD than those without at each blood pressure category. Systolic blood pressure, including the category of 130-139 mmHg, showed stronger associations with incident PAD than did diastolic blood pressure. Consequently, elevated blood pressure conferred similar or even greater risk of PAD than stage 1 hypertension, with implications on how to interpret new blood pressure categories in terms of leg vascular health.

Risk of Ischemic Stroke and Peripheral Arterial Disease in Heterozygous Familial Hypercholesterolemia: A Meta-Analysis.

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.

Relationship between pulmonary function and peripheral vascular function in older Chinese: Guangzhou biobank cohort study-CVD

BackgroundFindings describing the relationship between pulmonary function and peripheral vascular function have been inconclusive. We explored this relationship in Guangzhou Biobank Cohort Study-Cardiovascular Subcohort (GBCS-CVD).MethodsBrachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) were measured by a waveform analyser, and pulmonary function by turbine flowmeter spirometry. Predicted forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were derived using equations for Chinese. Regression analyses were used to investigate the association.ResultsOf 1528 older Chinese, 980 (64.1%) had arterial stiffness (baPWV ≥1400 cm/s), but only 29 (1.9%) had peripheral arterial disease (PAD) (ABI < 0.9). The mean (±standard deviation, SD) baPWV was 1547 (±298) cm/s and mean (±SD) ABI 1.09 (±0.09). Before and after adjusting for potential confounders, baPWV was negatively associated with FEV1 and FVC % predicted (% predicted = observed/predicted × 100%) (adjusted β: − 0.95 and − 1.16 respectively, p < 0.05), and ABI was marginally non-significantly positively associated with FEV1% predicted (adjusted β 0.02, p = 0.32) and FVC% predicted (adjusted β 0.02, p = 0.18). Compared to participants in the highest tertile of pulmonary function, those in the lowest had higher risk of arterial stiffness (adjusted odds ratio (AOR) 1.51, 95% CI 1.09–2.10 for FEV1 and AOR 1.69, 95% CI 1.22–2.33 for FVC), but the higher risk of PAD was marginally non-significant (AOR 1.64, p = 0.42 for FEV1 and AOR 1.65, p = 0.24 for FVC).ConclusionIn older relatively healthy normal weight Chinese, pulmonary function was inversely dose-dependently associated with arterial stiffness, while the association with PAD was much weaker.

High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study.

Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk. Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI. High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.