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As a generalised vascular disease, atherosclerosis can affect different vascular territories (carotid, coronary, lower limb, renal, and aorta) to different degrees. Polyvascular disease refers to atherosclerotic disease in more than one vascular territory. In contrast to the involvement of only one vascular territory, the multiple vascular territory form, as a varied phenotype, has been shown in numerous epidemiological studies to carry an increased cardiovascular risk (morbidity and mortality). While the recognition of the varied presentation is considered important for prognosis, given the screening vascular tests for disease detection are available, data on whether the detection of asymptomatic conditions by screening can meaningfully alter the treatment strategy are scarce. A subgroup analysis of new drug therapy trials suggests that proactive, intensive treatment of polyvascular disease (antilipemic, antithrombotic) is recommended, taking into account safety. There is a great need to design therapeutic clinical trials using different phenotypes of polyvascular disease as a study group. Optimal management of this high-risk group of patients requires effective multidisciplinary collaboration in patient management.

The document titled "2024 ESC Guidelines for the management of peripheral arterial and aortic diseases" is a comprehensive guide that provides recommendations for the evaluation, screening, and treatment of peripheral arterial and aortic diseases. It covers topics such as epidemiology, risk factors, and diagnostic methods for these conditions. The guidelines outline optimal medical treatments, including lifestyle changes and pharmacological therapies, and discuss specific conditions such as peripheral arterial disease and carotid artery disease. The document also addresses aortic diseases, including atheromatous disease and aortic aneurysms, and offers guidance on treatment options such as surgery and endovascular repair. It provides information on genetic and congenital diseases of the aorta, as well as polyvascular peripheral arterial disease. The document concludes with key messages, gaps in evidence, and recommendations for practice, emphasizing the importance of individualized care, multidisciplinary management, and early diagnosis. [Extracted from the article]

Purpose of Review: Polyvascular disease has a significant global burden and is associated with increased risk of major adverse cardiac events with each additional vascular territory involved. The purpose of this review is to highlight the risk factors, associated outcomes, emerging genetic markers, and evidence for screening and treatment of polyvascular disease. Recent Findings: Polyvascular disease is the presence of atherosclerosis in two or more vascular beds. It has a significant global burden, with a prevalence of 30–70% in patients with known atherosclerosis. Patients with polyvascular disease experience elevated rates of cardiovascular death, myocardial infarction and stroke, especially among high-risk subgroups like those with type 2 diabetes mellitus and there is a step-wise increased risk of adverse outcomes with each additional vascular territory involved. Genetic analyses demonstrate that some individuals may carry a genetic predisposition, while others exhibit higher levels of atherogenic lipoproteins and inflammatory markers. Routine screening for asymptomatic disease is not currently recommended by major cardiovascular societies unless patients are high-risk. While there are no established protocols for escalating treatment, existing guidelines advocate for lipid-lowering therapy. Additionally, recent studies have demonstrated benefit from antithrombotic agents, such as P2Y12 inhibitors and low-dose anticoagulation, but the optimal timing and dosage of these agents has not been established, and the ischemic benefit must be balanced against the increased risk of bleeding in the polyvascular population. Summary: Due to the high prevalence and risks associated with polyvascular disease, early identification and treatment intensification are crucial to reduce disease progression. Future research is needed to develop screening protocols and determine the optimal timing and dosing of therapy to prevent ischemic events. [ABSTRACT FROM AUTHOR]

Purpose: Patients with polyvascular disease (PVD) are at very high cardiovascular risk and require intensive lipid-lowering therapy. This analysis describes the lipid-lowering efficacy and safety of inclisiran versus placebo in patients with and without PVD. Methods: In this post hoc analysis of the ORION-9, ORION-10, and ORION-11 trials, patients were randomized 1:1 to receive 284 mg inclisiran (300 mg inclisiran sodium) or placebo on day 1, day 90, and 6-monthly thereafter. Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to day 510 and corresponding time-adjusted change from day 90 and up to day 540 were evaluated per patients' PVD status. Safety was assessed over 540 days. Results: Of 3454 patients, 470 (13.6%) had PVD, and 2984 (86.4%) did not. Baseline characteristics were generally balanced between the treatment arms in both cohorts. A greater proportion of patients with PVD had comorbidities versus those without. The mean (95% confidence interval [CI]) placebo-corrected LDL-C percentage change from baseline to day 510 was −48.9% (−55.6 to −42.2) in patients with PVD and −51.5% (−53.9 to −49.1) in patients without. Proportions of patients with reported treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events were similar between treatment arms, irrespective of PVD status, except for an excess of mild or moderate clinically relevant TEAEs at the injection site with inclisiran. Conclusion: Twice-yearly inclisiran dosing (after the initial and 3-month doses) was well tolerated and provided effective and sustained lipid-lowering in patients, irrespective of PVD status. [ABSTRACT FROM AUTHOR]

Patients with polyvascular disease (PVD), involving two or more vascular beds, are a difficult group for cardiologists, cardiovascular surgeons and endovascular surgeons. The relevance of the problem is due to its widespread prevalence, rapid progression, and comorbidity, which worsens the prognosis in this cohort of patients. The problem of selecting the optimal revascularization tactics remains unresolved. The results of original research on this problem are analyzed. The need for an individual multidisciplinary approach to determine the best revascularization strategy is demonstrated. The use of various methods of optimal therapy, open and endovascular surgery in each specific case is the most acceptable tactic.

Aim. To investigate the prevalence and characteristics of polyvascular disease in the Eurasian region's population with one or more previously established locations of atherosclerotic arterial damage, and to evaluate the diagnostic importance of the ankle-brachial index (ABI) as a marker for polyvascular disease (PVD).Material and methods. A total of 1837 patients were included in the main branch of the KAMMA registry (patients with PVD), among which 91,6% had coronary artery disease (CAD) (n=1683). For further analysis, the group of patients with CAD was combined with 1222 patients included in the second branch of the registry — KAMMA-cardio, forming a patient population (n=2905), in which all patients had verified CAD. The mean age of patients was 66,0 [59,0; 72,0] years, with 60,3% being male. Peripheral arteries was assessed using ultrasound examination.Results. PVD was present in 95,6% of patients with coronary atherosclerosis: dual-region involvement was observed in 51,3% of patients, three-region involvement in 37,1%, four-region involvement in 3,4%, and five-region involvement in 2,0%. Stenoses of the common carotid artery were observed in 71% of patients, internal carotid artery — in 68%, lower limb artery — in 52%, and renal and mesenteric artery — in 8,3%. There were following diagnostic effectiveness of the ABI for detecting patients with lower limb artery stenosis was: sensitivity — 58,0%, specificity — 83,6%. The quality of antithrombotic and lipid-lowering therapy was insufficient.Conclusion. In the overwhelming majority (95,6%) of patients with CAD in the KAMMA registry, PVD was revealed, with nearly half of the patients having involvement in three or more arterial zones. In the patient population with CAD, there should be an active effort to identify patients with PVD, using at least the ABI determination and active modern antithrombotic and lipid-lowering therapy according to current clinical guidelines.

Abstract Background Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). Methods In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. Results This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85–2.48) and stenosis (cOR, 1.47, 95% CI 1.26–1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24–1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P

Jieyao Xie, Tingjun Pan, Weiwen Luo, Songsheng Zhang, Yuquan Fang, Zhou Xu Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jieyao Xie, Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email X1275014370@163.comBackground: Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with multi-site atherosclerosis.Methods: The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed.Results: The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P=0.007) and rs4986893 G allele (97.7% vs 94.8%, P=0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups (P=0.002). The results of univariate logistic regression indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231– 0.902, P=0.024) may decrease risk of multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.780, 95% CI: 1.100– 2.880, P=0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: OR 0.459, 95% CI: 0.231– 0.909, P=0.026) may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.767, 95% CI: 1.091– 2.864, P=0.021) may be an independent risk factor for multi-site atherosclerosis.Conclusion: CYP2C19 *1/*3 genotype may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype may be an independent risk factor for multi-site atherosclerosis.Keywords: CYP2C19, genotype, multi-site atherosclerosis, polyvascular disease

Peripheral arterial disease (PAD) affects 12 % of adult population and is increasing globally and in India. Peripheral arterial disease when associated with atherosclerosis in two or more other arterial beds such as coronary artery disease (CAD), mesenteric/renal artery and cerebrovascular disease (CVD), is known as polyvascular disease. The Reduction of Atherothrombosis for Continued Health (REACH) registry reported that 1 out of 6 patients had multi-vascular bed involvement. Progression of PAD to critical limb ischaemia (CLI) is seen in 1 % of affected patients per year, but patients who progress to CLI may have a 10- to 15-fold increased risk of cardiovascular death.The 2019 ECS/EAS guidelines for the management of dyslipidaemias have suggested that for primary or secondary prevention in very high risk, patients should follow a therapeutic regimen that achieves >50 % LDL-C reduction from baseline and an LDL-C goal of

Background: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). Methods: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. Results: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85–2.48) and stenosis (cOR, 1.47, 95% CI 1.26–1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24–1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14–2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). Conclusions: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis. [ABSTRACT FROM AUTHOR]

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Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a difficult outcome to target, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD; however, the optimal intensity of such therapy is still a topic of debate, particularly in the post-acute and long-term setting. Recent well-powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and selection of patients is a key issue. The aim of this review is, therefore, to discuss and summarize the most up-to-date available evidence for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both types of atherosclerotic disease and comparing a higher- versus a lower-intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improve precision medicine. [ABSTRACT FROM AUTHOR]

Background: Statin therapy is recommended for patients with peripheral artery disease (PAD). However, PAD patients with polyvascular (PV) extent remain threatened by an increased residual cardiovascular (CV) risk. Purpose: To investigate the association of prescribed statin therapy and mortality in PAD patients with or without PV extent. Methods: A single-center retrospective longitudinal observational study originating from a consecutive registry with 1380 symptomatic PAD patients over a mean observational time of 60 ± 32 months. The association of atherosclerotic extent and statin use (PAD, plus one additional region (CAD or CeVD, [+1 V]), +2 vascular regions (+CAD and CeVD [+2 V]) with the risk of all-cause mortality was evaluated using Cox proportional hazard models adjusted for potential confounding factors. Results: The mean age of the study's participants was 72.0 ± 11.7 years, with 36% being female. PAD patients with PV extent [+1 V] and [+2 V] were older and suffered from diabetes, hypertension, or dyslipidemia more often; they, too, had more severely impaired kidney function (all p < 0.0001) compared to patients with PAD only. PAD patients with PV [+1 V] and [+2 V] received better statin medication and reached the recommended LDL-C target compared to PAD-only patients (p < 0.001). Despite better statin treatment, the rate of all-cause mortality was higher in PV patients than in PAD-only patients (PAD only: 13%; [+1 V]: 22%; [+2 V]: 35%; p < 0.0001). Conclusion: PV patients receive better statin therapy than PAD-only patients but nevertheless still have higher mortality rates. Future studies are needed to explore whether more aggressive LDL-lowering treatment for PAD patients may be translated into better prognosis. [ABSTRACT FROM AUTHOR]

Polyvascular disease affects up to 20% of atherosclerotic patients and portends a significantly higher cardiovascular risk, especially in terms of ischemic events. Therapeutic options mainly focus on aggressive pharmacotherapy and risk factor control. We present the case of a male obese patient with coronary artery disease, chronic renal disease, and refractory hypertension who underwent serial contrast imaging to document the extent and severity of his systemic atherosclerosis and was consequently referred for cardiovascular surgery to address total occlusion of the abdominal aorta. We further discuss specific features complicating the medical management of patients with severe hypertension, extensive atherosclerosis, and renal disease.

Recent genome-wide association studies have identified Phactr1 as a risk gene associated with polyvascular diseases. However, it remains elusive how Phactr1 is involved in the pathogenesis of vascular diseases. More recently, mounting evidence has suggested that PHACTR1 as an actin and protein phosphatase 1 binding protein, regulates endothelial proliferation, apoptosis, migration and tube formation, affects polarization in macrophages, and aggravates calcification in vascular smooth muscle cells. This paper focuses on the correlation between Phactr1 and polyvascular disease, and the molecular mechanism of Phactr1 in regulating atherosclerosis. We thus provided an overview of the role and therapeutic potential of Phactr1 in the progression of polyvascular disease.

Background: Heart failure (HF) is a growing public health problem and ischemic heart disease is an important risk factor. Understanding the epidemiology of HF in patients with atherosclerosis may help identify subgroups at greater risk who have the potential to derive greater benefit from preventive strategies. Methods and Results: The TRA 2°P‐TIMI 50 trial randomized 26,449 patients with stable atherosclerosis to the antiplatelet agent vorapaxar versus placebo. Hospitalization for HF (HHF) endpoints were adjudicated from serious adverse events by blinded structured review using established definitions. HHF incidence was estimated using Kaplan–Meier analysis. Independent predictors of HHF risk were identified using multivariable logistic regression. The effect of vorapaxar on HHF risk was explored using Cox regression. The estimated incidence of HHF at 3 years was 1.6%. Independent predictors of HHF included prior HF (adjusted odds ratio [adj‐OR]: 8.31; 95% confidence interval [CI]: 6.56–10.54), age (adj‐OR [per 10 years]: 1.67; 95% CI: 1.47–1.89), type 2 diabetes mellitus (T2DM; adj‐OR: 2.55; 95% CI: 2.01–3.24), polyvascular disease (two‐territory disease, adj‐OR: 1.89; 95% CI: 1.46–2.44; three‐territory disease, adj‐OR: 2.68; 95% CI: 1.94–3.70), chronic kidney disease (CKD; adj‐OR: 1.65; 95% CI: 1.30–2.11), body mass index (BMI; adj‐OR [per 5 kg/m2]: 1.15; 95% CI: 1.03–1.27), prior myocardial infarction (MI) (adj‐OR: 1.35; 95% CI: 1.03–1.78), and hypertension (adj‐OR: 1.44; 95% CI: 1.02–2.04). Patients who experienced HHF during follow‐up had higher rates of subsequent rehospitalization and death. Vorapaxar did not modify the risk of HHF. Conclusions: In patients with stable atherosclerosis, prior HF, age, T2DM, polyvascular disease, CKD, BMI, prior MI, and hypertension are important predictors of HHF risk. [ABSTRACT FROM AUTHOR]

Background Heterozygous familial hypercholesterolemia (HeFH) more likely exhibits extensive atherosclerotic disease at multiple vascular beds. Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein that elevates HeFH‐related atherosclerotic cardiovascular disease risks. Whether circulating Lp(a) level associates with polyvascular propagation of atherosclerosis in subjects with HeFH remains uncertain. Methods and Results The current study analyzed 370 subjects with clinically diagnosed HeFH who received evaluation of systemic arteries. Polyvascular disease (polyVD) was defined as more than 2 coexisting atherosclerosis conditions including coronary artery disease, carotid stenosis, or peripheral artery disease. Clinical characteristics and lipid features were analyzed in subjects with HeFH and polyVD; 5.7% of patients with HeFH (21/370) had polyVD. They were more likely to have a clustering of risk factors, tendon (P58 years old, family history of premature coronary artery disease, and Lp(a) ≥50 mg/dL (OR, 10.3 [95% CI, 3.12–33.4], P

The similarity of the pathogenesis of atherosclerosis and atherothrombotic complications, regardless of their location, makes the approaches to secondary prevention similar, which include lifestyle modification, pharmacotherapy of hemodynamic disorders, metabolic changes and hemostasis. Secondary prophylaxis in patients with multifocal arterial lesions using antihypertensive, antithrombotic and lipid-lowering therapy provides a more pronounced decrease in the incidence of cardiovascular complications than in lesions of single vascular lesions due to a higher initial risk. However, these treatments do not reduce the risk to the level that is achieved by treating patients with less atherosclerotic lesion. In this regard, it is of interest to use the currently available new methods and regimens of drug therapy in patients with multifocal arterial lesions, which make it possible to more intensively influence the mechanisms of atherosclerosis progression and more effectively prevent the development of its complications.

Polyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. The Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in more than one arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using the χ2 test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. Polyvascular disease was identified in 47% of CEA (39.0% in 2 arterial beds, 7.6% in 3 arterial beds; n = 93,736) and 47% of LEB (41.0% in 2 arterial beds, 5.7% in 3 arterial beds; n = 25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P <.0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% in 1 bed vs 1.5% in 2 beds vs 2.7% in 3 beds; P <.001) and LEB (2.2% in 1 bed vs 5.3% in 2 beds vs 6.6% in 3 beds; P <.001). Polyvascular disease was associated independently with perioperative MI/death after CEA (odds ratio, 1.59; 95% confidence interval [CI], 1.40-1.81; P <.0001) and LEB (odds ratio, 1.78; 95% CI, 1.52-2.08; P <.0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% in 3 beds vs 88% in 2 beds vs 92% in 1 bed; P <.01) and LEB (72% in 3 beds vs 75% in 2 beds vs 84% in 1 bed; P <.01) in a dose-dependent manner, with the lowest 5-year survival observed in those with three arterial beds involved. Polyvascular disease was independently associated with 5-year mortality after CEA (hazard ratio, 1.33; 95% CI, 1.24-1.40; P =.0001) and LEB (hazard ratio, 1.30; 95% CI, 1.20-1.41; P =.0001). Polyvascular disease is common in patients undergoing CEA and LEB and is associated with a higher risk of perioperative MI/death and decreased long-term survival. After revascularization, patients with polyvascular disease should be considered for more aggressive cardioprotective medications and closer follow-up. [ABSTRACT FROM AUTHOR]

Multifocal arterial disease is common in patients with atherosclerotic cardiovascular disease and is associated with an increased risk of cardiovascular complications and death. The possibility of improving the prognosis of patients with multifocal arterial disease is associated with a more efficient diagnosis of both the underlying disease and obstructive atherosclerotic lesions of other localizations and with a more intensive secondary prevention. According to observational studies, the presence of significant stenoses of the carotid arteries and, especially, lower extremities arterial disease can be predictorы of similar lesions in other vascular beds and their detection with screening methods available in clinical practice allows improvement of the diagnosis in patients with suspected coronary artery disease. On the other hand, screening of lower extremities artery diseases in patients with acute coronary syndrome can clarify indications for the use of invasive diagnostic and treatment strategy, in patients with chronic coronary artery disease it can justify more aggressive approaches to secondary prevention.

Background Peripheral artery disease (PAD) is associated with heightened risk for major adverse cardiovascular and limb events, but data on the burden of risk for total (first and potentially subsequent) events, and the association with polyvascular disease, are limited. This post hoc analysis of the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial evaluated total cardiovascular and limb events among patients with symptomatic PAD, overall and by number of symptomatic vascular territories. Methods and Results In the EUCLID trial, patients with symptomatic PAD (lower extremity revascularization >30 days before randomization or ankle‐brachial index ≤0.80) were randomized to treatment with ticagrelor or clopidogrel. Relative effects on total events (cardiovascular death; nonfatal myocardial infarction and ischemic stroke; acute limb ischemia, unstable angina, and transient ischemic attack requiring hospitalization; coronary, carotid, and peripheral revascularization procedures; and amputation for symptomatic PAD) were summarized by hazard ratios (HRs), whereas absolute risks were estimated by incidence rates and mean cumulative functions. Among 13 885 randomized patients, 7600 total cardiovascular and limb events occurred during a median 2.7 years of follow‐up, translating to 60.0 and 62.5 events per 100 patients through 3 years for the ticagrelor and clopidogrel groups, respectively (HR, 0.96; 95% CI, 0.89–1.03; P=0.27). Among 1393 patients with disease in 3 vascular territories, event accrual rates through 3 years for the ticagrelor and clopidogrel groups were 87.3 and 97.7 events per 100 patients, respectively. Absolute risk reductions for ticagrelor relative to clopidogrel at 3 years were −0.2, 6.7, and 10.3 events per 100 patients for 1, 2, and 3 affected vascular territories, respectively (Pinteraction=0.09). Conclusions Patients with symptomatic PAD have nearly double the number of total events than first events, with rates reflecting the number of affected vascular territories. These findings highlight the clinical relevance of quantifying disease burden in terms of total events and the need for long‐term preventive treatments in high‐risk patient populations. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT01732822.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle–brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle–brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement. [ABSTRACT FROM AUTHOR]

Background and Aims: The Mediterranean Diet (MD) represents a key player in cardiovascular disease prevention. Therefore, we aimed to assess the relationship between adherence to the MD and inflammatory, lipid and glycemic profile in patients affected by polyvascular atherosclerotic disease (PAD). We also investigated the incidence of long-term major adverse cardiovascular events (MACEs) according to MD adherence.Methods and Results: We enrolled 107 patients with PAD, defined as the simultaneous involvement of at least two vascular districts. Adherence to the MD was estimated through a 9-item simplified form of the Mediterranean Diet Score. Improved fasting glycemic and LDL-cholesterol levels were reported in the high-adherence group compared with the low-adherence group (p < 0.001 and p = 0.0049, respectively). Both C-reactive protein and platelet-to-lymphocyte ratio were significantly lower in high-adherence patients than those with poor adherence to the MD (p = 0.0045 and p = 0.008, respectively). During follow-up (mean 34 ± 11 months), fatal events happened exclusively in the low-adherence group (58%), with an event-free survival of 37% compared with 87% in the moderate-adherence group and 70% in the high-adherence group (log-rank p-value < 0.001). Low adherence to the MD was associated with a higher incidence of MACEs in the Cox regression model adjusted for atherosclerotic risk factors (HR 12.23, 95% CI 4.00-37.39).Conclusions: High adherence to Mediterranean dietary pattern seems to be associated with improving inflammatory and metabolic status in patients suffering from PAD, potentially translating into better long-term cardiovascular outcomes. These findings provide evidence regarding the relevance of MD as a secondary preventive tool in this high-risk population. [ABSTRACT FROM AUTHOR]

Polyvascular disease is an independent predictor of major adverse cardiovascular events (MACE). The relationship between the number of diseased arterial beds and MACE is unknown. How MACE risk changes in individuals with type 2 diabetes (T2D) is also understudied. Furthermore, it is unknown whether heart failure (HF) status and hemoglobin A1c (HbA1c) levels influence outcomes in polyvascular disease. This analysis from the Exenatide Study of Cardiovascular Event Lowering trial (EXSCEL) aimed to examine the risk associated with increasing number of diseased arterial beds on MACE and all-cause mortality (ACM). Cox models were used to test associations between the number of diseased arterial beds and MACE and ACM. Prespecified interaction testing between number of diseased arterial beds with baseline HF, HbA1c (≤8% vs. >8%), and treatment assignment was performed. Overall, 14,751 participants were included; 26.5% were without atherosclerosis, 58.9% had 1-bed, 12.3% had 2-bed, and 2.3% had 3-bed disease. An increasing burden of atherosclerotic disease was associated with increasing risk of MACE (adjusted HR [aHR] 1.71 [95% CI 1.46–2.02]; 2.61 [2.17–3.15]; 3.46 [2.69–4.45] for 1, 2, and 3 beds, respectively, p < 0.001 for all) and ACM (1.94 [1.56–2.42]; 3.03 [2.33–3.95]; 3.66 [2.59–5.18] for 1, 2, and 3 beds, respectively, p < 0.001 for all). Prespecified interaction testing did not reveal any significant associations. In patients with T2D, compared to those without atherosclerotic vascular disease, risk of MACE and ACM increases incrementally with each additional diseased arterial bed. [Display omitted] • Polyvascular disease is an independent predictor of adverse outcomes including major adverse cardiovascular events (MACE) and all-cause mortality (ACM). • The relationship between the number of diseased arterial beds and MACE, especially in patients with type 2 diabetes (T2D), is unknown. • This analysis from the EXSCEL trial demonstrated that in patients with T2D, compared to those without atherosclerotic vascular disease, risk of MACE and ACM increases incrementally with each additional diseased arterial bed. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to examine the association of polyvascular disease and clinical outcomes in patients with lacunar stroke.Methods: Data of patients with recent lacunar stroke were collected from The Third China National Stroke Registry. Polyvascular disease is defined as the existence of atherosclerosis across two or more vascular beds. For the present study, polyvascular disease patients were grouped as follows: coronary heart disease (CHD) and lacunar stroke, peripheral arterial disease (PAD) and lacunar stroke, and CHD/PAD and lacunar stroke. The major clinical outcome was recurrence, and the secondary clinical outcome was major adverse cardiovascular events (MACEs). A Cox proportional multivariable hazards regression model was applied to estimate the association between polyvascular disease and outcomes.Results: Among 3,165 patients with recent lacunar stroke, CHD was present in 375 (11.8%) and peripheral arterial disease in 168 (5.3%). The hazard ratio (HR) for stroke recurrence was 0.98 (95% confidence interval [CI], 0.65–1.46; p = 0.91) for patients with CHD and lacunar stroke, 1.07 (95% CI, 0.61–1.87; p = 0.82) for patients with PAD and lacunar stroke, and 0.95 (95% CI, 0.66–1.35; p = 0.75) for patients with CHD/PAD and lacunar stroke compared with patients with isolated lacunar stroke. The HR for MACEs was 1.01 (95% CI, 0.69–1.49; p = 0.94) for patients with CHD and lacunar stroke, 1.11 (95% CI, 0.65–1.90; p = 0.71) for patients with PAD and lacunar stroke, and 0.99 (95% CI, 0.70–1.40; p = 0.95) for patients with CHD/PAD and lacunar stroke.Conclusion: Polyvascular disease is not associated with recurrence of stroke and MACEs in patients with recent lacunar stroke at 1 year.

Clinical implications of systemic atherosclerosis in patients with cardiogenic shock (CS) remain unclear. This study investigated the association between polyvascular disease (PVD) and clinical outcome in CS patients. A total of 1247 CS patients was enrolled from the RESCUE registry, a multicenter, observational cohort between January 2014 and December 2018. They were divided into two groups according to presence of PVD, defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, or cerebrovascular disease. Primary outcome was all-cause death during 12 months of follow-up. 136 (10.9%) patients were diagnosed with PVD. The risk of 12-month all-cause death was significantly higher in the PVD group than in the non-PVD group (54.4% versus 40.4%, adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.02–1.69, p = 0.034). There was a significant interaction between PVD and vasoactive inotropic score (VIS) (p for interaction = 0.014). Among the 945 patients with VIS <84, PVD was associated with a higher risk of 12-month all-cause death (unadjusted HR 1.77, 95% CI 1.30–2.41, p = 0.030); among the 302 patients with VIS ≥84, the incidence of 12-month all-cause death was similar between the PVD and non-PVD groups (unadjusted HR 1.03, 95% CI 0.68–1.56, p = 0.301). Presence of PVD was associated with 12-month all-cause mortality in patients with CS, especially for less severe forms of CS patients with VIS <84. Clinical trials.gov number: NCT02985008 • Polyvascular disease was associated with higher mortality in cardiogenic shock. • Prognostic role of polyvascular disease was notable in less severe cardiogenic shock. • Polyvascular disease was related to poor prognosis in shock requiring vasopressors. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to examine the association of polyvascular disease and clinical outcomes in patients with lacunar stroke. Methods: Data of patients with recent lacunar stroke were collected from The Third China National Stroke Registry. Polyvascular disease is defined as the existence of atherosclerosis across two or more vascular beds. For the present study, polyvascular disease patients were grouped as follows: coronary heart disease (CHD) and lacunar stroke, peripheral arterial disease (PAD) and lacunar stroke, and CHD/PAD and lacunar stroke. The major clinical outcome was recurrence, and the secondary clinical outcome was major adverse cardiovascular events (MACEs). A Cox proportional multivariable hazards regression model was applied to estimate the association between polyvascular disease and outcomes. Results: Among 3,165 patients with recent lacunar stroke, CHD was present in 375 (11.8%) and peripheral arterial disease in 168 (5.3%). The hazard ratio (HR) for stroke recurrence was 0.98 (95% confidence interval [CI], 0.65–1.46; p = 0.91) for patients with CHD and lacunar stroke, 1.07 (95% CI, 0.61–1.87; p = 0.82) for patients with PAD and lacunar stroke, and 0.95 (95% CI, 0.66–1.35; p = 0.75) for patients with CHD/PAD and lacunar stroke compared with patients with isolated lacunar stroke. The HR for MACEs was 1.01 (95% CI, 0.69–1.49; p = 0.94) for patients with CHD and lacunar stroke, 1.11 (95% CI, 0.65–1.90; p = 0.71) for patients with PAD and lacunar stroke, and 0.99 (95% CI, 0.70–1.40; p = 0.95) for patients with CHD/PAD and lacunar stroke. Conclusion: Polyvascular disease is not associated with recurrence of stroke and MACEs in patients with recent lacunar stroke at 1 year. [ABSTRACT FROM AUTHOR]

Patients with peripheral artery disease (PAD) and end-stage kidney disease are a high-risk population, and concomitant atherosclerosis in coronary arteries (CAD) or cerebral arteries (CVD) is common. The aim of the study was to assess long-term outcomes of PAD and the impact of coexistent CAD and CVD on outcomes. The United States Renal Data System was used to identify patients with PAD within 6 months of incident dialysis. Four groups were formed: PAD alone, PAD with CAD, PAD with CVD, and PAD with CAD and CVD. PAD-specific outcomes (chronic limb-threatening ischemia, major amputation, percutaneous/surgical revascularization, and their composite, defined as major adverse limb events [MALE]) as well as all-cause mortality, myocardial infarction, and stroke were studied. The study included 106,567 patients (mean age, 71.2 years; 40.8% female) with a median follow-up of 546 days (interquartile range, 214-1096 days). Most patients had PAD and CAD (49.8%), 25.8% had PAD alone, and 19.2% had all three territories involved. MALE rate in patients with PAD was 22.3% and 35.0% at 1 and 3 years, respectively. In comparison to PAD alone, the coexistence of both CAD and CVD (ie, polyvascular disease) was associated with a higher adjusted rates of all-cause mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.24-1.31), myocardial infarction (HR, 1.78; 95% CI, 1.69-1.88), stroke (HR, 1.66; 95% CI, 1.52,1.80), and MALE (HR, 1.07; 95% CI, 1.04-1.11). Patients with end-stage kidney disease have a high burden of PAD with poor long-term outcomes, which worsen, in an incremental fashion, with the involvement of each additional diseased arterial bed. [ABSTRACT FROM AUTHOR]

Aim. To estimate the prevalence of inflammatory residual risk in patients with stable atherosclerotic cardiovascular disease (ASCVD) and establish the relationship between concentration of C-reactive protein (CRP) and the presence of the polyvascular disease.Materials and Methods. The study included 120 patients with stable ASCVD. The plan of the instrumental study included ultrasound scanning of the carotid arteries and lower limb arteries with measurement of the ankle-brachial index. The concentration of hsCRP in the serum was determined by the enzyme-linked immunosorbent assay.Results. An increase in the content of hsCRP ≥ 2,0 mg/l was detected in 45,8% of patients. Clinically significant lesion of one vascular bed was observed in 41,6% of patients, two – in 36,6%, three – in 21,6%. In the group of patients with atherosclerosis of the three vascular beds, the median value of hsCRP was 3,28 (1,77–5,67) mg/l, which was statistically significantly higher compared to patients with the involvement of one vascular bed – 1,56 (0,68–3,92) mg/L. An increase in hsCRP over 2,0 mg/l was associated with an increase in the relative risk of a patient with polyvascular disease with a atherosclerosis of three vascular beds 3,63 times (95% CI 1,06–12,4; p = 0,04) with adjusting for gender, age, obesity, diabetes, smoking, cholesterol levels and glomerular filtration rate.Conclusion. Inflammatory residual risk was observed in 45,8% of patients with stable ASCVD. An increase in CRP was established with an increase in the number of affected vascular beds. An increase in hsCRP over 2,0 mg/l was independently associated with an increase in the relative risk of a patient having an polyvascular disease.

Aim: To determine the relationship between polyvascular disease and risk of hospitalization for heart failure (HHF) and cardiovascular (CV) death in the EMPA‐REG OUTCOME population, and the relationship of kidney dysfunction co‐existent with polyvascular disease on CV/heart failure (HF) outcomes. Materials and Methods: Patients with type 2 diabetes and atherosclerotic CV (ASCVD) received empagliflozin 10, 25 mg or placebo. Post hoc, subgroups were analyzed by one versus two or more vascular beds, and the estimated glomerular filtration rate ([eGFR] < vs. ≥60 mL/min/1.73 m2) at baseline. The empagliflozin arms were pooled. Time to CV death, HHF, CV death (excluding fatal stroke) or HHF, all‐cause mortality (ACM) and 3‐point major adverse CV events (3P‐MACE) were assessed using multivariable Cox regression models. Results: Baseline characteristics (N = 6959) within subgroups were balanced between treatment groups. In the placebo group, two or more versus one vascular bed increased HHF risk (1.59 [95% confidence interval 1.02, 2.49]), CV death (2.17 [1.52, 3.09]), CV death/HHF (1.79 [1.32, 2.43]), ACM (1.95 [1.44, 2.64]) and 3P‐MACE (1.76 [1.36, 2.27]). Hazard ratios for those with polyvascular disease/kidney dysfunction (vs. 1 vascular bed/eGFR ≥60 mL/min/1.73 m2) were HHF 2.80 (1.46, 5.36), CV death 3.10 (1.87, 5.13), CV death/HHF 2.71 (1.74, 4.23), ACM 2.59 (1.67, 4.02) and 3P‐MACE 2.62 (1.82, 3.77). Empagliflozin reduced the risk of all outcomes across subgroups. Conclusions: Polyvascular disease with/without kidney dysfunction markedly increases the risk of HF/CV events. Empagliflozin consistently reduces risk, regardless of vascular bed and kidney function status. [ABSTRACT FROM AUTHOR]

Background: Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear.Methods: Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients.Results: A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6

Background: Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear. Methods: Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients. Results: A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6<2.64 pg/mL patients, patients had non-PolyVD with IL-6 ≥ 2.64 pg/mL (HR 1.245 95%CI 1.072–1.446; P < 0.001) and PolyVD with IL-6 <2.64 pg/mL (HR 1.251 95%CI 1.002–1.563; P = 0.04) were associated with an increased risk of recurrent stroke during 1-year follow-up. Likewise, patients with PolyVD and IL-6 ≥ 2.64 pg/mL (HR 1.290; 95% CI 1.058–1.572; P = 0.01) had the highest risk of recurrent stroke at 1-year follow-up among groups. Conclusion: PolyVD and elevated IL-6 levels are both associated with poor outcomes in patients with AIS or TIA. Moreover, the combination of them increases the efficiency of stroke risk stratification compared with when used alone. More attention and intensive treatment should be given to those patients with both PolyVD and elevated IL-6 levels. [ABSTRACT FROM AUTHOR]

Background: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI)., Methods and results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71)., Conclusions: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Background Atherosclerosis in >1 vascular bed (ie, polyvascular disease), often a feature of peripheral artery disease (PAD), is associated with high morbidity and mortality. We sought to identify risk factors for polyvascular involvement in patients with PAD. Methods and Results We performed 2‐sample Mendelian randomization using an inverse‐variance‐weighted approach, to assess 60 exposures including size and lipid content of atherogenic lipoproteins, blood pressure, glycated hemoglobin, and smoking as causal mediators for polyvascular disease in patients with PAD. Genetic instruments for these exposures were obtained from prior genome‐wide association studies. Patients with PAD were from the Mayo Vascular Disease Biorepository, and polyvascular disease (ie, concomitant coronary heart disease, cerebrovascular disease, and/or abdominal aortic aneurysm) was ascertained by validated phenotyping algorithms. Of 3279 patients with PAD, 61% had polyvascular disease. Genetically predicted levels of the lipid content and/or particle measures of very small and small size very low‐density lipoprotein, intermediate‐density lipoprotein, and large low‐density lipoprotein were associated with polyvascular disease: odds ratios (OR) of 1.80 (95% CI, 1.23–2.61), 1.70 (95% CI, 1.17–2.61), and 1.40 (95% CI, 1.09–1.80) per 1 SD increase in genetically determined levels, respectively. Both genetically predicted diastolic and systolic blood pressure were associated with polyvascular disease; OR per 10 mm Hg genetic increase in diastolic and systolic blood pressure were 1.66 (95% CI, 1.19–2.33) and 1.31 (95% CI, 1.07–1.60), respectively. Conclusions Lifetime exposure to increased lipid content and levels of very small and small very low‐density lipoprotein, intermediate‐density lipoprotein, and large low‐density lipoprotein particles as well as elevated blood pressure are associated with polyvascular involvement in patients with PAD. Reduction in levels of such exposures may limit progression of atherosclerosis in patients with PAD.

Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with coronary artery disease or lower extremity peripheral artery disease. Thirteen trials were included ranging in size from 7243 to 27,395 patients. In 9 trials (CHARISMA, TRA 2°P–TIMI 50, PEGASUS—TIMI 54, VOYAGER PAD, TRACER, EUCLID, TRILOGY ACS, PLATO, and COMPASS), patients in the PVD subgroup treated with increased-intensity antithrombotic therapy had similar or greater relative risk reductions for ischemic events in comparison with the general trial cohorts. In four trials (DAPT, THEMIS, APPRAISE-2, and ATLAS ACS 2 TIMI 51), the PVD subgroup had an increased hazard of ischemic events with increased-intensity therapy compared with the general trial cohorts. More intense antithrombotic therapy in patients with PVD was associated with a similar relative risk reduction for ischemic events compared with patients without PVD. Therefore, patients with PVD benefit from a larger absolute risk reduction because of their higher baseline risk. Future trials in patients with atherosclerotic cardiovascular disease should intentionally include PVD patients to adequately assess treatment options for this under-studied, under-treated population. Image 1 • Polyvascular disease (PVD) is a strong independent risk factor for ischemic outcomes. • We reviewed 13 antithrombotic RCTs ranging in size from 7243 to 27,395 patients. • We assessed if increased intensity therapy improved ischemic outcomes in PVD. • PVD patients had similar or greater ischemic risk reduction with more intense therapy. • Intensive therapy in PVD does not seem to be associated with increased bleeding risk. [ABSTRACT FROM AUTHOR]

Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (–2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether theWalking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during twoyear follow-up. Design: A prospective observational study. Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital. Participants: Patients admitted with acute Non-STEMI-or STEMI-elevation myocardial infarction. Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile. Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%). Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease is a frequently underdiagnosed disease that can severely affect the quality of life. We present a clinical case of a 62-year-old smoker post-menopause woman with a mild stroke. Further investigation revealed a severe disseminated arterial disease. Due to multidisciplinary and timely interventions, peripheral ischemia was prevented successfully. In fact, this patient had polyvascular disease. Despite its worst prognosis than either coronary artery disease, cerebrovascular disease, or peripheral arterial disease alone, polyvascular disease is still underdiagnosed. Atherosclerosis and cardiovascular risk should be regarded as multisystemic and managed as such in multidisciplinary teams. A proper and timely intervention is essential to diminish its morbidity and mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Costa et al.)

Background: Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 ( CYP2C19 ) polymorphisms with multi-site atherosclerosis., Methods: The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed., Results: The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P =0.007) and rs4986893 G allele (97.7% vs 94.8%, P =0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups ( P =0.002). The results of univariate logistic regression indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231-0.902, P =0.024) may decrease risk of multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.780, 95% CI: 1.100-2.880, P =0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: OR 0.459, 95% CI: 0.231-0.909, P =0.026) may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.767, 95% CI: 1.091-2.864, P =0.021) may be an independent risk factor for multi-site atherosclerosis., Conclusion: CYP2C19 *1/*3 genotype may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype may be an independent risk factor for multi-site atherosclerosis., Competing Interests: The authors declare that they have no competing interests in this work., (© 2023 Xie et al.)

Aims: The aim of this study was to investigate the association between serum total bilirubin concentration and complicated macrovascular diseases, such as cerebrovascular disease (CBVD), cardiovascular disease (CAD), and peripheral arterial disease (PAD), in patients with type 2 diabetes.Methods: We performed a retrospective cross-sectional study in 674 patients with type 2 diabetes. Serum total bilirubin concentration was compared between patients with and without CBVD, CAD, and PAD. Logistic regression analyses were performed to identify risk factors for CBVD, CAD, and PAD. Associations between total bilirubin concentration and the number of complicated macrovascular diseases were analyzed.Results: Patients with CBVD and PAD showed significantly lower serum total bilirubin concentrations than did those patients without those diseases. However, the bilirubin concentration did not differ between patients with and without CAD. Total bilirubin concentration was an independent predictor of CBVD, but not of CAD or PAD. There was a statistically significant trend for a decrease in bilirubin concentration in the presence of an increasing number of macrovascular diseases.Conclusion: The presence of more than one macrovascular disease, called polyvascular disease, carries a high risk for cardiovascular mortality. Serum total bilirubin concentration may be useful as a clinical biomarker of polyvascular disease. [ABSTRACT FROM AUTHOR]

Paul Y Takahashi, Casey R Caldwell, Paul V TargonskiPrimary Care Internal Medicine, Mayo Clinic, Rochester MN, USABackground: Vascular dementia (VaD) is a challenging illness that affects the lives of older adults and caregivers. It is unclear how multiple vascular risk factor exposures (polyvascular disease) affect VaD.Purpose: To determine the relationship between multiple vascular risk exposures, as counted on an index in cases with VaD, compared with healthy age-/gender-matched controls.Methods: This was a matched case-control study of subjects living in Olmsted County, MN with documented VaD. Controls were selected by gender and age within 3 years from those who did not have dementia. The exposures included a total index (eleven exposure factors) added together, along with indexes for cerebrovascular disease (two exposures), cardiovascular disease (four exposures), vascular disease (three exposures), and lifestyle (two exposures). Analysis used matched conditional univariable logistic regression for each index.Results: A total of 1736 potential subjects were identified, and 205 subjects were diagnosed with VaD. There was a significant association of the total score index with an odds ratio of 1.45 (95% confidence interval 1.21–1.74). The cerebrovascular index was also associated with VaD with an odds ratio of 12.18 (95% confidence interval 6.29–23.61). The cardiovascular and vascular indexes were also associated with VaD status. The lifestyle index was not associated with VaD.Conclusion: The cumulative role of multiple vascular risk factors or diseases increased the risk of VaD, as noted by the total vascular index. The lifestyle index did not reveal any significant differences. Further work is required for evaluation of these indexes.Keywords: polyvascular disease, elderly, vascular dementia

Although during the last decade there have been great advances in our knowledge of the epidemiology and pathophysiology of multi-district atherosclerotic disease, little is known about the association between peripheral arterial disease and carotid artery disease. This review was conceived to cast some light on this topic, paying special attention to inflammation which plays a pivotal role in atherosclerosis. An aspect of pathophysiologic and clinical relevance is that the coexistence of carotid disease is more frequent in peripheral arterial disease than in coronary artery disease, not only in terms of carotid stenosis, but also with respect to the presence of hypoechoic unstable plaque. These latter plaques present a large infiltration of macrophages and are associated to high levels of inflammatory markers. In particular, the greater prevalence of hypoechoic carotid plaques in peripheral arterial disease compared to patients with carotid artery disease was poorly related to classic risk factors, but showed an independent association with an increased number of leukocyte and neutrophil cells, which are reliable markers of inflammation. The greater prevalence of hypoechoic unstable carotid plaques could explain why peripheral arterial disease portends higher risk of stroke than coronary artery disease.

Background Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI. Method 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds. Results A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p < 0.001), diabetes (p = 0.039), previous PAD (p = 0.009) and female gender (p = 0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7–79.2%) and specificity of 92.4% (95% CI 89.5–95.4%). Conclusions PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients. [ABSTRACT FROM AUTHOR]