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

BACKGROUND: To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318). METHODS: 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. RESULTS: 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. DISCUSSIONS: 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.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study.

BACKGROUND: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. METHODS: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). RESULTS: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. CONCLUSIONS: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

Prevalence and Burden of Carotid and Femoral Atherosclerosis in Subjects Without Known Cardiovascular Disease in a Large Community Hospital in South-America.

INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.

Health and lifestyle parameters in peripheral artery disease at two periods of the COVID-19 pandemic: comparison between men and women.

OBJECTIVE: This study analyzed the impact of sex on self-reported health and lifestyle parameters in peripheral artery disease patients at two periods of the COVID-19 pandemic. METHODS: In this longitudinal study, 99 patients with peripheral artery disease (53 men and 46 women) were evaluated during two periods of the COVID-19 pandemic ( i.e ., at onset: May to August 2020, and on follow-up: May to August 2021). Patients were interviewed via telephone, and information regarding lifestyle and health parameters was obtained. RESULTS: At the onset of the COVID-19 pandemic, health and habit parameters were similar between women and men, with 63.0% and 45.3% indicating frequent fatigue, 73.9% and 84.9% reporting increased sitting time, and 23.9% and 39.6% practicing physical activity, respectively. At follow-up, difficulties in physical mobility (women: from 26.1% to 73.9%, p<0.001; men: from 39.6% to 71.7%, p=0.001) and the frequency of hospitalization for reasons other than COVID-19 increased similarly in women and men (women: from 4.3% to 21.7%, p=0.013; men: from 9.4% to 24.5%, p=0.038). The other parameters were similar between the periods. CONCLUSION: Self-reported physical mobility difficulties and hospitalization frequency increased in women and men with peripheral artery disease. BACKGROUND: ▪ Sitting time increased in 73.9% of women and 84.9% of men at the onset of the pandemic. BACKGROUND: ▪ Physical activity was practiced by 23.9% of women and 39.6% of men at the onset of the pandemic. BACKGROUND: ▪ The prevalence of both women and men reporting physical mobility difficulties increased at follow-up. BACKGROUND: ▪ Hospitalization rates for reasons unrelated to COVID-19 have increased in both women and. BACKGROUND: While women experience more consequences related to peripheral artery disease than men, such as worse functional capacity and higher morbidity, there was a similar increase in physical mobility difficulty and frequency of hospitalization for reasons other than COVID-19 one year after the onset of the pandemic.

Peripheral artery disease mediating the effect of metabolic syndrome related diseases on lower limb ulcers: Mendelian randomization analysis.

Background: Previous observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored. Method: This research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD. Results: Univariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD. Conclusion: Hypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.

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

BACKGROUND: The objective of this study was to investigate the relationship between the prognostic nutritional index (PNI) and peripheral artery disease (PAD). METHODS: The 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. RESULTS: A 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. CONCLUSIONS: In 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.

Association Between Cardiovascular Event Type and Smoking Cessation Rates Among Outpatients With Atherosclerotic Cardiovascular Disease: Insights From the NCDR PINNACLE Registry.

BACKGROUND: It is unclear how the type of an atherosclerotic cardiovascular disease (ASCVD) event potentially influences patients' likelihood of smoking cessation. METHODS: Using 2013 to 2018 data from the US based National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient cardiac registry, we identified patients who were current smokers at a clinic visit and followed them over time for a subsequent ASCVD event. Self-reported smoking status was assessed at each consecutive visit and used to determine smoking cessation after each interim ASCVD event (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke/transient ischemic attack, peripheral artery disease). We constructed separate multivariable Cox models with nonproportional hazards to examine the association of each interim ASCVD event with smoking cessation, compared with not having an interim ASCVD event. We estimated the relative association of ASCVD event type with smoking cessation using contrast tests. Analyses were stratified by presence versus absence of ASCVD at baseline. RESULTS: Across 530 cardiology practices, we identified 1 933 283 current smokers (mean age 62±15, male 54%, ASCVD at baseline 50%). Among the 322 743 patients who had an interim ASCVD event and were still smoking, 41 336 (12.8%) quit smoking by their first subsequent clinic visit, which was higher among those with baseline ASCVD (13.4%) as compared with those without baseline ASCVD (11.5%). Each type of ASCVD event was associated with an increased likelihood of smoking. Patients who had an myocardial infarction, underwent coronary artery bypass graft (hazard ratio, 1.60 [95% CI, 1.55-1.65]), or had a stroke or transient ischemic attack were more likely to quit smoking as compared with those who underwent elective percutaneous coronary intervention or had a new diagnosis of peripheral artery disease (hazard ratio, 1.20 [95% CI, 1.17-1.22]). CONCLUSIONS: Only 13% of patients reported smoking cessation after an ASCVD event, with the type of event being associated with the likelihood of smoking cessation, prompting the need for patient-centered interventions.

Awareness of smoking cessation amongst German vascular surgeons.

Background: Smoking represents the well-known enemy of vascular well-being. Numerous previous studies emphasised the important role of smoking on the development and progression of atherosclerotic cardiovascular disease. The current study aimed to identify hurdles and barriers for an insufficient implementation of secondary prevention in the treatment of lower extremity peripheral arterial disease (PAD). Methods: All members of the German Society for Vascular Surgery and Vascular Medicine (DGG) with valid email addresses were invited to participate in an electronic survey on smoking. Results are descriptively presented. Results: Amongst 2716 invited participants, 327 (12%) submitted complete responses, thereof 33% women and 80% between 30 and 59 years old (87% board certified specialists). 83% were employed by hospitals (56% teaching hospital, 14% university, 13% non-academic) and 16% by outpatient facilities. 6% are active smokers (63% never) while a mean of five medical education activities on smoking cessation were completed during the past five years of practice. Only 27% of the institutions offered smoking cessation programs and 28% of the respondents were aware of local programs while a mean of 46% of their patients were deemed eligible for participation. 63% of the respondents deemed outpatient physicians primarily responsible for smoking cessation, followed by medical insurance (26%). Conclusions: The current nationwide survey of one scientific medical society involved in the care of patients with vascular disease revealed that smoking cessation, although being commonly accepted as important pillar of comprehensive holistic care, is not sufficiently implemented in everyday clinical practice.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. METHODS: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age. RESULTS: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years. CONCLUSIONS: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression.

Prevalence and determinants of self-reported low-fat-, low-salt-, and vegetarian diets in patients with cardiovascular disease between 1996 and 2019.

BACKGROUND AND AIMS: Guidelines no longer recommend low-fat diets and currently recommend more plant-based diets to reduce atherosclerotic cardiovascular disease (ASCVD) risk. Furthermore, these guidelines have consistently recommended salt-reduced diets. This article describes current self-reported use and time-trends in the self-reported use of low-fat, low-salt and vegetarian diets in ASCVD patients and examines patient characteristics associated with each diet. METHODS AND RESULTS: 9005 patients with ASCVD included between 1996 and 2019 in the UCC-SMART cohort were studied. The prevalence of self-reported diets was assessed and multi-variable logistic regression was used to identify the determinants of each diet. Between 1996-1997 and 2018-2019, low-fat diets declined from 22.4 % to 3.8 %, and low-salt diets from 14.7 % to 4.6 %. The prevalence of vegetarian diets increased from 1.1 % in 1996-1997 to 2.3 % in 2018-2019. Patients with cerebrovascular disease (CeVD) and peripheral artery disease or an abdominal aortic aneurysm (PAD/AAA) were less likely to report a low-salt diet than coronary artery disease (CAD) patients (OR 0.62 [95%CI 0.49-0.77] and 0.55 [95%CI 0.41-0.72]). CONCLUSION: In the period 1996 to 2019 amongst patients with ASCVD, the prevalence of self-reported low-fat diets was low and decreased in line with changes in recommendations in major guidelines. The prevalence of self-reported vegetarian diets was low but increased in line with societal and guideline changes. The prevalence of self-reported low-salt diets was low, especially in CeVD and PAD/AAA patients compared to CAD patients, and decreased over time. Renewed action is needed to promote low-salt diets in ASCVD patients.

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross-sectional study.

Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross-sectional study. The outcome was PAD, which defined as an ankle-brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60-17.80) µmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06-1.19). Patients in the upper plasma Hcy tertile (≥16.16 µmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33 µmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

Ultrasonic AccV: a potential indicator of peripheral arteriosclerosis in patients with chronic obstructive pulmonary disease.

OBJECTIVE: This study aimed to investigate the risk factors for peripheral arteriosclerosis (PAS) and peripheral artery disease (PAD) in chronic obstructive pulmonary disease (COPD) patients and potential ultrasound indicators that could be used to improve detection. METHOD: Outpatients seeking care between January 1, 2017, and December 31, 2020, in The First Affiliated Hospital of China Medical University were prospectively recruited. Subjects were divided into COPD and non-COPD (control) groups, and the COPD group was further divided into PAD and non-PAD subgroup, at the same time, PAS and non-PAS subgroup. Indicators of PAD -ankle-brachial index (ABI), indicators of PAS- pulse wave velocity (PWV), and ultrasound indices -peak systolic blood flow velocity (PSV) and blood flow acceleration velocity (AccV) were compared. RESULT: Sixty-nine (61.6%) of 112 enrolled subjects had COPD. COPD patients had higher age, and blood pressure (BP)lower than controls. Seventeen (24.6%) COPD patients had PAD, the prevalence of PAD increases with the decrease of lung function, and seven (16.3%) non-COPD patients had PAD, however, there was no significant statistical difference between COPD and non-COPD groups. Fifty (72.5%) COPD patients had PAS, and thirty-four (79.1%) non-COPD patients had PAS, however, there was also no significant difference. The PAS subgroup had higher age, body mass index(BMI), body fat percentage(BFP), lower FEV1 and FEV1/FVC, as well as higher levels of right brachial artery and left dorsalis pedis artery AccV. Factors that correlated with ABI were 6MWD, post-bronchodilator FEV1, FEV1/ FVC, and maximal middle expiratory flow between 75% and 25% of FVC. Age, BP, and 6MWD, but not pulmonary function, were associated with brachial-ankle PWV (baPWV). There was a positive correlation between baPWV and radial artery AccV bilaterally. CONCLUSION: Radial artery AccV correlated well with baPWV, which suggests that ultrasound could be used to assess both morphological and functional changes in vessels, may serving as a better method to identify PAS in high-risk COPD patients.

Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors.

BACKGROUND: Major depressive disorder (MDD) has been identified as a causal risk factor for multiple forms of cardiovascular disease. Although observational evidence has linked MDD to peripheral artery disease (PAD), causal evidence of this relationship is lacking. METHODS AND RESULTS: Inverse variance weighted 2-sample Mendelian randomization was used to test the association the between genetic liability for MDD and genetic liability for PAD. Genetic liability for MDD was associated with increased genetic liability for PAD (odds ratio [OR], 1.17 [95% CI, 1.06-1.29]; P=2.6×10-3). Genetic liability for MDD was also associated with increased genetically determined lifetime smoking (ß=0.11 [95% CI, 0.078-0.14]; P=1.2×10-12), decreased alcohol intake (ß=-0.078 [95% CI, -0.15 to 0]; P=0.043), and increased body mass index (ß=0.10 [95% CI, 0.02-0.19]; P=1.8×10-2), which in turn were associated with genetic liability for PAD (smoking: OR, 2.81 [95% CI, 2.28-3.47], P=9.8×10-22; alcohol: OR, 0.77 [95% CI, 0.66-0.88]; P=1.8×10-4; body mass index: OR, 1.61 [95% CI, 1.52-1.7]; P=1.3×10-57). Controlling for lifetime smoking index, alcohol intake, and body mass index with multivariable Mendelian randomization completely attenuated the association between genetic liability for MDD with genetic liability for PAD. CONCLUSIONS: This work provides evidence for a possible causal association between MDD and PAD that is dependent on intermediate risk factors, adding to the growing body of evidence suggesting that effective management and treatment of cardiovascular diseases may require a composite of physical and mental health interventions.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

Association between red cell distribution width-and-albumin ratio and the risk of peripheral artery disease in patients with diabetes.

Aim: The aim of this study is to explore the association between red blood cell distribution width-to-albumin ratio (RAR) and the risk of peripheral artery disease (PAD) in patients with diabetes. Methods: This cross-sectional study extracted the data of 1,125 participants with diabetes from the National Health and Nutrition Examination Survey database. A weighted univariable logistic regression model was used to explore variables associated with PAD. With PAD as the outcome variable, a weighted logistic regression model was established. The odds ratio (OR) and 95% confidence interval (CI) were effect size. Results: After adjusting for covariates, the risk of PAD in patients with diabetes was observed in those with higher RAR (OR = 1.83; 95% CI: 1.06-3.15). In addition, RAR ≥3.25 was related to increased risk of PAD in patients with diabetes (OR = 2.04; 95% CI: 1.05-3.95). In people with diabetes aged ≥65, RAR was a risk factor for PAD with an OR value of 2.67 (95% CI: 1.30-5.46). RAR ≥3.25 was associated with increased risk of PAD (OR = 3.06; 95% CI: 1.15-8.11) relative to RAR <2.80. In people with diabetes who smoked, the risk of PAD was elevated in those with RAR ≥3.25 (OR = 2.85; 95% CI: 1.28-6.32). As for patients with cardiovascular disease, the risk of PAD was elevated as the increase of RAR (OR = 2.31; 95% CI: 1.05-5.10). RAR ≥3.25 was correlated with increased risk of PAD (OR = 3.75; 95% CI: 1.42-9.87). The area under the curve of RAR for the risk of PAD in patients with diabetes was 0.631 (95% CI: 0.588-0.675). Conclusion: A higher RAR was related to increased risk of PAD in patients with diabetes. The findings might offer a reference for the management of PAD in patients with diabetes.

Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Arterial involvement of lower limbs in peripheral artery disease - the difference between diabetics and non-diabetics.

OBJECTIVE: To detect peripheral artery disease in diabetic and non-diabetic individuals. METHODS: The case-control study was conducted from October 2018 to September 2019 at Ruth K.M. Pfau Civil Hospital, Karachi, and comprised diagnosed diabetic patients with random blood sugar ≥200mg/dl in group A, and healthy non-diabetic subjects in group B. Ankle brachial pressure index was measured and mean luminal diameters of lower limb arteries were compared using colour Doppler ultrasonography. Data was analysed using SPSS 21. RESULTS: Of the 82 subjects, 41(50%) were in each of the 2 groups. The sample had 42(51.2%) males and 30(48.8%) females with overall mean age of 53.9±5.07 years (range 44-60 years). There was significant difference in the ankle brachial pressure index values between the groups (p=0.004). There was also a significant difference in the mean luminal diameters of distal arteries (p=0.001), while there was no significant difference in proximal arteries (p>0.05). CONCLUSIONS: The diabetics were more prone to developing peripheral arterial disease than nondiabetics.

Temporal trends in characteristics and outcomes after myocardial infarction in patients with and without peripheral artery disease - A Nationwide, register-based follow-up study.

AIM: Patients with peripheral artery disease (PAD) represent a high-risk population with increased morbidity and mortality. We aimed to examine trends in myocardial infarction (MI), PAD and adverse clinical outcomes from years 2000 to 2019. METHODS: This nationwide Danish-based registry study included all patients with MI from years 2000-2019. Patients with PAD were compared to patients without PAD. Temporal changes in PAD prevalence over time was examined using the Cochrane-Armitage trend test, and Cox regression was used to test for between-group significance in all care and outcome measures. RESULTS: A total of 196,635 patients experienced an MI within the study time frame; the prevalence of PAD over time showed a slight increase (p < 0.01). Patients with MI and a concurrent PAD diagnosis elicited a heavier burden of comorbidities. The primary MACE endpoint showed significant decreases in both patients with and without PAD (p < 0.01); the decrease was more marked in patients without a concurrent PAD diagnosis (p < 0.01) alongside with 1-year all-cause mortality (p < 0.01). There was a slight increase in initiation of preventive pharmacotherapy with a prominent increase in initiation of P2Y12-inhibitors post discharge in patients without PAD in comparison to patients with PAD, and the same pattern applied for lipid lowering agents (p < 0.01). Also, there was an increase in revascularization in patients with MI but more markedly in patients without coexisting PAD. CONCLUSIONS: Despite significant decreases in MACE and mortality and significant increases in guideline-recommended care and revascularization over time for MI patients both with and without PAD, improvement in all these measures was less prominent in patients with MI and concomitant PAD.