Association of the triglyceride-glucose index with early-onset atherosclerotic cardiovascular disease events and all-cause mortality: a prospective cohort study.

BACKGROUND: The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. METHODS: The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. RESULTS: During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38-1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17-1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear < 0.01), and a linear association between TyG index and all-cause mortality (P for non-linear = 0.476). CONCLUSIONS: A higher TyG index is significantly associated with an increased incidence of early-onset ASCVD events and all-cause mortality in a young and middle-aged population from North China.

Demographic and regional trends of peripheral artery disease-related mortality in the United States, 2000 to 2019.

INTRODUCTION: Peripheral artery disease (PAD) is a common progressive atherosclerotic disease associated with significant morbidity and mortality in the US; however, data regarding PAD-related mortality trends are limited. This study aims to characterize contemporary trends in mortality across sociodemographic and regional groups. METHODS: The Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) was queried for data regarding PAD-related deaths from 2000 to 2019 in the overall sample and different demographic (age, sex, race/ethnicity) and regional (state, urban-rural) subgroups. Crude and age-adjusted mortality rates (CMR and AAMR, respectively) per 100,000 people were calculated. Associated annual percentage changes (APC) were computed using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. RESULTS: Between 2000 and 2019, a total of 1,959,050 PAD-related deaths occurred in the study population. Overall, AAMR decreased from 72.8 per 100,000 in 2000 to 32.35 per 100,000 in 2019 with initially decreasing APCs followed by no significant decline from 2016 to 2019. Most demographic and regional subgroups showed initial declines in AAMRs during the study period, with many groups exhibiting no change in mortality in recent years. However, men, non-Hispanic (NH) Black or African American individuals, people aged ⩾ 85 years, and rural counties were associated with the highest AAMRs of their respective subgroups. Notably, there was an increase in crude mortality rate among individuals 25-39 years of age from 2009 to 2019. CONCLUSION: Despite initial improvement, PAD-related mortality has remained stagnant in recent years. Disparities have persisted across several demographic and regional groups, requiring further investigation.

Atherosclerosis: Known and unknown.

Atherosclerotic disease, such as myocardial infarction and stroke, is the number one killer worldwide. Atherosclerosis is considered to be caused by multiple factors, including genetic and environmental factors. In humans, it takes several decades until the clinical complications develop. There are many known risk factors for atherosclerosis, including hypercholesterolemia, hypertension, diabetes and smoking, which are involved in the pathogenesis of atherosclerosis; however, it is generally believed that atherosclerosis is vascular chronic inflammation initiated by interactions of these risk factors and arterial wall cells. In the past 30 years, the molecular mechanisms underlying the pathogenesis of atherosclerosis have been investigated extensively using genetically modified animals, and lipid-reducing drugs, such as statins, have been demonstrated as the most effective for the prevention and treatment of atherosclerosis. However, despite this progress, questions regarding the pathogenesis of atherosclerosis remain and there is a need to develop new animal models and novel therapeutics to treat patients who cannot be effectively treated by statins. In this review, we will focus on two topics of atherosclerosis, "pathology" and "pathogenesis," and discuss unanswered questions.

Oral GLP-1 analogue: perspectives and impact on atherosclerosis in type 2 diabetic patients.

Cardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug's antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management.

Atherogenic index of plasma is associated with major adverse cardiovascular events in patients with type 2 diabetes mellitus.

BACKGROUND: Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). METHODS: This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. RESULTS: AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. CONCLUSIONS: This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

The expression of miR-211-5p in atherosclerosis and its influence on diagnosis and prognosis.

BACKGROUND: The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. METHODS: A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan-Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. RESULTS: The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r = - 0.639, P < 0.001) and CIMT (r = - 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). CONCLUSION: Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.

What Do US Physicians and Patients Think About Lipid-Lowering Therapy and Goals of Treatment? Results From the GOULD Registry.

Background Because of an increasing number and complexity of treatment options for lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision-making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid-lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low-density lipoprotein cholesterol (LDL-C) control (LDL-C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid-lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL-C level, and 69% did not know their LDL-C goal. Patients on PCSK9 inhibitors (versus LDL-C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient-reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid-lowering medications, current LDL-C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision-making and treatment adherence. Registration URL: https://www.clinicaltrials.org; Unique identifier: NCT02993120.

Cardiac pathology in COVID-19: a single center autopsy experience.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19). METHODS: Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization. In the case of out-of-hospital death, patients were included if post-mortem testing was positive. Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination. If available, laboratory findings and echocardiograms were reported. RESULTS: The median age of the decedents was 63.5 years. The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%). Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients. Acute myocardial ischemia was observed in eight (16.0%) patients. The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%). The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients. CONCLUSIONS: Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings. Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes. A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed.

Natural history of penetrating atherosclerotic ulcers in aortic branch vessels.

OBJECTIVE: Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs. METHODS: Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model. RESULTS: Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm. CONCLUSIONS: This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare-the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed.

Serum albumin and risks of hospitalization and death: Findings from the Atherosclerosis Risk in Communities study.

OBJECTIVES: To determine whether lower serum albumin in community-dwelling, older adults is associated with increased risk of hospitalization and death independent of pre-existing disease. DESIGN: Prospective cohort study of participants in the fifth visit of the Atherosclerosis Risk in Communities (ARIC) study. Baseline data were collected from 2011 to 2013. Follow-up was available to December 31, 2017. Replication was performed in Geisinger, a health system in rural Pennsylvania. SETTING: For ARIC, four US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota. PARTICIPANTS: A total of 4947 community-dwelling men and women aged 66 to 90 years. EXPOSURE: Serum albumin. MAIN OUTCOMES: Incident all-cause hospitalization and death. RESULTS: Among the 4947 participants, mean age was 75.5 years (SD: 5.12) and mean baseline serum albumin concentration was 4.05 g/dL (SD: 0.30). Over a median follow-up period of 4.42 years (interquartile interval: 4.16-5.05), 553 participants (11.2%) died and 2457 participants (49.7%) were hospitalized at least once. The total number of hospitalizations was 5725. In analyses adjusted for demographics and numerous clinical characteristics, including tobacco use, obesity, frailty, cardiovascular disease, kidney disease, diabetes C-reactive protein (CRP), cognitive status, alcohol use, medication use, respiratory disease, and systolic blood pressure, 1 g/dL lower baseline serum albumin concentration was associated with higher risk of both hospitalization (incidence rate ratio [IRR]: 1.58; 95% confidence interval [CI]: 1.36-1.82; p < 0.001) and death (hazard ratio [HR]: 1.67; 95% CI: 1.24-2.24; p < 0.001). Associations were weaker with older age but not different by frailty status or level of high-sensitivity CRP. Associations between serum albumin, hospitalizations, and death were also similar in a real-world cohort of primary care patients. CONCLUSIONS: Lower baseline serum albumin was significantly associated with increased risk of both all-cause hospitalization and death, independent of pre-existing disease. Older adults with low serum albumin should be considered a high-risk population and targeted for interventions to reduce the risk of adverse outcomes.

Effects of Anthocyanins on Vascular Health.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis.

BACKGROUND: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. OBJECTIVE: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. METHODS: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan-Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. RESULTS: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 -1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 -1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 -1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 -1.117], p = 0.017). CONCLUSION: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.

LDL cholesterol and atherosclerosis: The evidence. / Colesterol LDL y aterosclerosis: evidencias.

The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development. Multiple experimental, epidemiological, and clinical evidence underpins this association. Atherosclerotic cardiovascular disease remains as the major cause of mortality in the world. Recent genetic studies of Mendelian randomisation and randomised clinical trials aimed at LDL cholesterol reduction, are summarised in this article. They, unequivocally ratify the aetiological role of LDL cholesterol in the development of atherosclerosis. Thus, LDL cholesterol lowering is the cornerstone of lipid lowering therapy for the reduction of cardiovascular complications of atherosclerosis.

Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease.

BACKGROUND: Obesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown. OBJECTIVES: The aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes. METHODS: A screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints. RESULTS: Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects. CONCLUSIONS: These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183).

Soluble ST2, a biomarker of fibrosis, is associated with multiple risk factors, chronic diseases and total mortality in the OPERA study.

Several diseases have a deleterious fibrosis component. Biomarkers indicating potential clinical utility that reliably reflect the degree of fibrosis have been introduced, one of them being soluble suppression of tumorigenicity 2 (sST2). The aim of our study was to explore the association of cardiometabolic risk factors, different diseases and total mortality with biomarker sST2 and see, how fibrosis is portrayed in these conditions. In addition, we were interested to see if sST2 levels could predict fibrosis in the long-term (21 years). The Oulu Project Elucidating Risk of Atherosclerosis (OPERA) survey collected data on the same individuals in years 1991-1993 (baseline, n = 1045), 2013-2014 (follow-up, n = 600) and mortality data until year 2019. Smoking at baseline retained a significant association with sST2 levels reflecting fibrosis development 20 years later. In the multivariate model male gender, diabetes, quick-index, levels of alanine aminotransferase (ALAT), high-density lipoprotein (HDL) cholesterol and high-sensitivity C-reactive protein (hsCRP) were associated with elevated sST2 levels at the examination 2013-2014. sST2 levels were higher among subjects suffering from cardiovascular disease (p = .031), cancer (p = .021), mild cognitive decline (p = .046) and diabetes (p < .001). Total mortality was assessed by using the Cox proportional hazard survival model analysis. sST2 (log-transformed) was an independent predictor of total mortality (HR 9.4; 95% CI 2.8-31.4, p<.001) when age, gender, diabetes, smoking, quick-index, levels of ALAT, HDL-cholesterol and hsCRP were added as covariates. In addition, elevated levels indicated worse prognosis and predicted mortality.

Prestroke Physical Activity and Adverse Health Outcomes After Stroke in the Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: The association of physical activity (PA) before stroke (prestroke PA) with long-term prognosis after stroke is still unclear. We examined the association of prestroke PA with adverse health outcomes in the ARIC study (Atherosclerosis Risk in Communities). METHODS: We included 881 participants with incident stroke occurring between 1993 and 1995 (visit 3) and December 31, 2016. Follow-up continued until December 31, 2017 to allow for at least 1-year after incident stroke. Prestroke PA was assessed using a modified version of the Baecke questionnaire in 1987 to 1989 (visit 1) and 1993 to 1995 (visit 3), evaluating PA domains (work, leisure, and sports) and total PA. We used Cox proportional hazards models to quantify the association between tertiles of accumulated prestroke PA levels over the 6-year period between visits 1 and 3 and mortality, risk of cardiovascular disease, and recurrent stroke after incident stroke. RESULTS: During a median follow-up of 3.1 years after incident stroke, 676 (77%) participants had adverse outcomes. Highest prestroke total PA was associated with decreased risks of all-cause mortality (hazard ratio, 0.78 [95% CI, 0.63-0.97]) compared with lowest tertile. In the analysis by domain-specific PA, highest levels of work PA were associated with lower risk for all-cause (hazard ratio, 0.77 [95% CI, 0.62-0.96]) and cardiovascular mortality (hazard ratio, 0.45 [95% CI, 0.29-0.70]), and highest levels of leisure PA were associated with lower all-cause mortality (hazard ratio, 0.72 [95% CI, 0.58-0.89]) compared with lowest tertile of PA. No significant associations for sports PA were observed. CONCLUSIONS: Higher levels of total prestroke PA as well as work and leisure PA were associated with lower risk of mortality after incident stroke. Public health strategies to increase lifetime PA should be encouraged to decrease long-term mortality after stroke.

Prognostic value of malnutrition using geriatric nutritional risk index in patients with coronary chronic total occlusion after percutaneous coronary intervention.

BACKGROUND: Malnutrition is associated with poor prognosis in a wide range of chronic illnesses, however, the impact of malnutrition on long-term outcomes of patients at advanced stages of atherosclerosis, coronary chronic artery occlusion (CTO), is not known. AIMS: This study aims to investigate the relationship between malnutrition and adverse cardiovascular events in patients with CTO after percutaneous coronary intervention (PCI). METHODS: Baseline malnutrition risk was determined in 669 patients with CTO after PCI in this study. All patients were divided into 3 groups according to 3 categories of the geriatric nutritional risk index (GNRI): moderate to severe, GNRI of <92 (n = 70); low, GNRI of 92-98 (n = 197); and absence of risk, GNRI of ≥98 (n = 402). The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE). RESULTS: Average age in this study was 65.32 ± 9.97 years old. More than one-third of patients were at risk of malnutrition (moderate to severe: 10.5%; low: 29.4%; and absence of risk: 60.1%). Over a median follow-up of 33 months, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the all-cause death, cardiovascular death and MACE (hazard ratio [HR]: 2.90, 95% confidence interval [CI]: 1.43 to 5.87, P for trend = 0.002; HR: 3.72, 95% CI: 1.42 to 9.77, P for trend = 0.010; HR: 1.76, 95% CI: 1.02 to 3.03, P for trend = 0.040; respectively) after adjustment for baseline variables. Moreover, addition of the GNRI score significantly raised the predictive value for the all-cause death (0.383, p = 0.004 and 0.022, p = 0.011, NRI and IDI respectively), cardiovascular death (0.488, p < 0.001 and 0.013, p = 0.014, NRI and IDI respectively) and MACE (0.368, p = 0.004 and 0.014, p = 0.008, NRI and IDI respectively) as compared to traditional factors. CONCLUSIONS: Malnutrition assessed by the GNRI score on admission was an independent predictor for adverse cardiovascular events in CTO patients after PCI. Addition of the GNRI score to the existing risk prediction model significantly increased the predictive ability for cardiovascular events in CTO patients after PCI.

Long-Term Mortality After Renal Artery Stenting in Patients With Severe Atherosclerotic Renal Artery Stenosis and High-Risk Clinical Manifestations.

BACKGROUND: Atherosclerotic renal artery stenosis is a risk factor for cardiovascular death. Observational studies support the benefit of renal revascularization on outcomes in patients with high-risk clinical manifestations. In this context, we evaluated the factors associated with long-term mortality after renal artery stenting in patients with severe renal artery stenosis, impaired kidney function, and/or uncontrolled hypertension. METHODS: The medical records of patients undergoing renal artery stenting between 2004 and 2014 were extracted. Blood pressure and creatinine were recorded at baseline, 24 hours poststenting and in the 1-month to 1-year interval that followed revascularization. Long-term follow-up was performed in March 2020. RESULTS: The cohort consisted of 65 patients. Median follow-up was 120 months. In the first year after stenting, less patients had chronic kidney disease (CKD) class 3b-5 as compared with baseline (35.3% vs. 56.9%, P = 0.01). The number of patients with controlled blood pressure after revascularization increased with 69.2% (P < 0.001). Long-term all-cause mortality reached 44.6%. Age (odds ratio (OR) 1.1; 95% confidence interval (CI) 1.0-1.2; P = 0.01), male gender (OR 7.9; 95% CI 1.9-43.5; P = 0.008), poststenting CKD class 3b-5 (OR 5.8; 95% CI 1.5-27.9; P = 0.01), and postrevascularization uncontrolled hypertension (OR 8.9; 95% CI 1.7-63.5; P = 0.01) were associated with long-term mortality independent of diabetes mellitus and coronary artery disease. CONCLUSIONS: Improved CKD class and blood pressure were recorded in the first year after renal artery stenting in patients with severe renal artery stenosis and high-risk clinical manifestations. The lack of improvement in kidney function and blood pressure was independently associated with long-term mortality.

High HDL-Cholesterol Paradox: SCARB1-LAG3-HDL Axis.

PURPOSE OF THE REVIEW: To evaluate recent studies related to the paradox of high HDL-C with mortality and atherosclerotic cardiovascular disease (ASCVD) risk. RECENT FINDINGS: Two observational studies (Cardiovascular Health in Ambulatory Care Research Team [CANHEART] and Copenhagen City Heart Study and the Copenhagen General Population Study [Copenhagen Heart Studies]) of adults without pre-existing ASCVD have shown a significant U-shaped association of HDL-C with all-cause and cause-specific mortality. Both studies showed that low HDL-C levels consistently increased hazard risk (HR) for all-cause and cause-specific mortality. In the CANHEART study, high HDL-C levels, HDL-C > 90 mg/dL, were associated with increased HR for non-CVD/non-cancer mortality. In the Copenhagen Heart Studies, women with HDL-C ≥ 135 mg/dL showed increased HR for all-cause and CVD mortality, while men with HDL-C > 97 mg/dL showed increased HR for all-cause and CVD mortality. Genetic association studies failed to show that genetic etiologies of high HDL-C significantly reduced risk for myocardial infarction (MI), while hepatocyte nuclear factor-4 (HNF4A) was significantly associated with high HDL-C and increased MI risk. Candidate gene studies have identified scavenger receptor B class I (SCARB1) and lymphocyte activation gene-3 (LAG3) as genes significantly associated with high HDL-C and increased MI risk. Low HDL-C remains as a significant factor for increased disease risk while high HDL-C levels are not associated with cardioprotection. Clinical CVD risk calculators need revision.

Independent association of atherogenic dyslipidaemia with all-cause mortality in individuals with type 2 diabetes and modifying effect of gender: a prospective cohort study.

BACKGROUND: Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes. METHODS: This observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006-2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and TG:HDL. RESULTS: There were 3,602 deaths over a follow-up 7.42 ± 2.05 years (31.0 × 1000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total, LDL, or non-HDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055-1.291], p = 0.003) and TG:HDL (1.192 [1.082-1.314], p < 0.0001) and the lowest HDL cholesterol (1.232 [1.117-1.360], p < 0.0001) quartile, though the association of triglycerides and HDL cholesterol disappeared after further adjustment for each other. Interaction with gender was significant only for HDL cholesterol (p = 0.0009). The relationship with death was stronger for triglycerides in males and HDL cholesterol in females, with these associations remaining significant even after adjustment for HDL cholesterol (1.161 [1.019-1.324], p = 0.025, for the highest vs the lowest triglyceride quartile) and triglycerides (1.366 [1.176-1.587], p < 0.0001, for the lowest vs the highest HDL cholesterol quartile). CONCLUSIONS: In patients with type 2 diabetes, higher triglycerides and TG:HDL and lower HDL cholesterol were independently associated with increased all-cause mortality, with a modifying effect of gender for triglycerides and HDL cholesterol. These data suggest that atherogenic dyslipidaemia, especially TG:HDL, may serve as predictor of all-cause death in these individuals. Trial registration ClinicalTrials.gov, NCT00715481, 15 July, 2008.