Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population.Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45).ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.     

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events

BackgroundIntensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients.ObjectivesThe aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment.MethodsThis was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment.ResultsAmong 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = ?0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality.ConclusionsSPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)     

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis

Background and aimsPrevious studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients.Methods and resultsIn this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6–71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06–1.93, P = 0.019), 1.54 (95%CI = 1.01–2.35, P = 0.046), respectively.ConclusionHigher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.     

Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies

AimsCirculating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.Data synthesisA total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26–1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46–2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose–response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89–0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32–0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65–0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).ConclusionsThe lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events.     

Haptoglobin Phenotype Modifies the Influence of Intensive Glycemic Control on Cardiovascular Outcomes

BackgroundWhereas there exists a direct relationship between glycated hemoglobin and cardiovascular disease (CVD), clinical trials targeting glycated hemoglobin to near-normal levels using intensive therapy have failed to prevent CVD and have even increased mortality, making clinical decision making difficult. A common polymorphism at the haptoglobin (Hp) genetic locus is associated with CVD, especially coronary heart disease, in the setting of hyperglycemia.ObjectivesThis study sought to determine whether the treatment difference of intensive versus standard glucose-lowering therapy on risk of CVD events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study depended on Hp phenotype.MethodsHp phenotype was measured within 5,806 non-Hispanic white ACCORD participants using a validated assay. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different Hp phenotype groups (Hp2-2, Hp1 carriers).ResultsCompared with standard therapy, intensive therapy was associated with a lower risk of incident coronary heart disease among participants with the Hp2-2 phenotype (n = 2,133; aHR: 0.71; 95% CI: 0.55 to 0.91; p = 0.006), but not among the other 2 phenotypes (Hp1 allele carriers) (n = 3,673; aHR: 0.95; 95% CI: 0.79 to 1.13; p = 0.550). The same pattern was observed for CVD. Conversely, intensive therapy was associated with an increased risk of fatal CVD (aHR: 1.50; 95% CI: 1.00 to 2.25; p = 0.049) and total mortality (aHR: 1.40; 95% CI: 1.08 to 1.81; p = 0.011) among the Hp1 carriers, whereas this risk was not increased in the Hp2-2 phenotype (fatal CVD: aHR: 1.02; 95% CI: 0.59 to 1.77; p = 0.931; total mortality: aHR: 0.98; 95% CI: 0.68 to 1.41; p = 0.908).ConclusionsIntensive glucose-lowering therapy was effective at preventing incident coronary heart disease and CVD events in ACCORD study participants with the Hp2-2 phenotype but not in Hp1 carriers, who had increased mortality risk from intensive therapy.     

Recovery of Left Ventricular Systolic Function and Clinical Outcomes in Young Adults With Myocardial Infarction

BackgroundLeft ventricular ejection fraction (EF) recovery is associated with better long-term outcomes after myocardial infarction (MI). However, the association between long-term outcomes and EF recovery among young MI patients has not been investigated.ObjectivesThis study sought to evaluate the prevalence of left ventricular systolic dysfunction among patients who experience their first MI at a young age and to compare outcomes between those who recovered their EF versus those who did not.MethodsThe YOUNG-MI registry is a retrospective cohort study of patients who experienced an MI at ≤50 years of age. EF at the time of MI and within 180 days post-MI were determined from all available medical records. The primary outcomes were all-cause and cardiovascular mortality.ResultsThere were 1,724 patients with baseline EF data: 503 (29%) had EF <50%, whereas 1,221 (71%) had a normal baseline EF. Patients with lower EF were more likely to have experienced ST-segment elevation MI, have higher troponin values, and have more severe angiographic coronary artery disease. Among patients with abnormal baseline EF, information on follow-up EF was available for 216, of whom 90 (42%) recovered their EF to ≥50%. Patients who experienced EF recovery had less severe angiographic disease, lower alcohol use, and a lower burden of comorbidities. Over a median follow-up of 11.1 years, EF recovery was associated with an ∼8-fold reduction in all-cause mortality (adjusted hazard ratio: 0.12; p = 0.001) and a ∼10-fold reduction in cardiovascular mortality (adjusted hazard ratio: 0.10; p = 0.025).ConclusionsNearly one-third of young patients presented with left ventricular dysfunction post-MI. Among them, EF recovery occurred in more than 40% and was independently associated with a substantial decrease in all-cause and cardiovascular mortality.     

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).     

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies

BackgroundCardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer therapy. Yet, whether CVD events were consistently reported in pivotal trials supporting contemporary anticancer drugs is unknown.ObjectivesThe authors sought to evaluate the incidence, consistency, and nature of CVD event reporting in cancer drug trials.MethodsFrom the Drugs@FDA, clinicaltrials.gov, MEDLINE, and publicly available U.S. Food and Drug Administration (FDA) drug reviews, all reported CVD events across latter-phase (II and III) trials supporting FDA approval of anticancer drugs from 1998 to 2018 were evaluated. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction, stroke, heart failure, coronary revascularization, atrial fibrillation, or CVD death, irrespective of treatment arm. The secondary outcome was report of any CVD event. Pooled reported annualized incidence rates of MACE in those without baseline CVD were compared with reported large contemporary population rates using relative risks. Population risk differences for MACE were estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios on the basis of the presence or absence of reported CVD were also assessed.ResultsOverall, there were 189 trials, evaluating 123 drugs, enrolling 97,365 participants (58.5 ± 5 years, 46.0% female, 72.5% on biologic, targeted, or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 30 months, 1,148 incidents of MACE (375 heart failure, 253 myocardial infarction, 180 strokes, 65 atrial fibrillation, 29 revascularizations, and 246 CVD deaths; 792 in the intervention vs. 356 in the control arm; p < 0.01) were reported from the 62.4% of trials noting any CVD. The overall weighted-average incidence was 542 events per 100,000 person-years (716 per 100,000 in the intervention arm), compared with 1,408 among similar-aged non-cancer trial subjects (relative risk: 0.38; p < 0.01), translating into a risk difference of 866. There was no association between reporting CVD events and drug efficacy (hazard ratio: 0.68 vs. 0.67; p = 0.22).ConclusionsAmong pivotal clinical trials linked to contemporary FDA-approved cancer drugs, reported CVD event rates trail expected population rates.     

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients

Background and aimsRemnant cholesterol (RC) adversely contributes to cardiovascular disease (CVD) and overall survival in various diseases. However, its role in CVD outcomes and all-cause mortality in patients undergoing peritoneal dialysis (PD) is limited. Therefore, we aimed to investigate the association between RC and all-cause and CVD mortality in patients undergoing PD.Methods and resultsBased on lipid profiles recorded using standard laboratory procedures, fasting RC levels were calculated in 2710 incident patients undergoing PD who were enrolled between January 2006 and December 2017 and followed up until December 2018. Patients were divided into four groups according to the quartile distribution of baseline RC levels (Q1: <0.40 mmol/L, Q2: 0.40 to <0.64 mmol/L, Q3: 0.64 to <1.03 mmol/L, and Q4: ≥1.03 mmol/L). Associations between RC and CVD and all-cause mortality were evaluated using multivariable Cox models. During the median follow-up period of 35.4 months (interquartile range, 20.9–57.2 months), 820 deaths were recorded, of which 438 were CVD-related. Smoothing plots showed non-linear relationships between RC and adverse outcomes. The risks of all-cause and CVD mortality increased progressively through the quartiles (log-rank, p < 0.001). Using adjusted proportional hazard models, a comparison of the highest (Q4) to lowest (Q1) quartiles revealed significant increases in the hazard ratio (HR) for all-cause mortality (HR 1.95 [95% confidence interval (CI), 1.51–2.51]) and CVD mortality risk (HR 2.60 [95% CI, 1.80–3.75]).ConclusionAn increased RC level was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that RC was important clinically and required further research.     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

Triglycerides and Residual Atherosclerotic Risk

BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Sex-discrete role of depressive symptomatology on 10-year first and recurrent cardiovascular disease incidence: results from ATTICA and GREECS prospective studies

ObjectiveThe sex-specific effect of depressive symptomatology on 10-year first and recurrent cardiovascular disease (CVD) events was evaluated.MethodsThe Greek samples from ATTICA (2002-2012, n = 845 free-of-CVD subjects) and GREECS (2004-2014, n = 2,172 subjects with acute coronary syndrome (ACS)) prospective epidemiological studies with baseline psychological assessments were used for the first and the recurrent event, respectively. Depressive symptomatology was assessed at baseline, through Zung Self-Rating Depression Scale in the ATTICA study, and through the Center for Epidemiological Studies-Depression scale in the GREECS study.ResultsACS as well as free-of-CVD women scored significantly higher for depressive symptomatology. Men scored higher than women against first (19.7% vs. 11.7%) and subsequent CVD events (38.8% vs. 32.9%). In participants with depressive symptoms man-to-woman first and recurrent CVD event rate ratio was below 1, confirming that depressive women were more likely to have a CVD event than depressive men. Multiadjusted analysis revealed that depressive symptomatology had an independent aggravating effect on the first (hazard ratio (HR) = 2.72, 95% confidence interval (95% CI) 1.50, 9.12) and recurrent (HR = 1.31, 95% CI 1.01, 1.69) CVD events only in women. Mediation analysis in women revealed that 35% (23%, 44%) of excess first-CVD-event risk of depressive symptoms was attributed to conventional risk factors. The respective number for recurrent CVD events was 46% (23%, 53%); different patterns of ranking regarding the mediating effect corresponding to each adjustment factor were observed.ConclusionsThe present work augments prior evidence that psychological stressors possess important drivers of CVD onset and progression mainly in women, while it gives rise to research toward unidentified paths behind this claim.     

Outcomes of Drug-Eluting Stent Thrombosis After Treatment for Acute Versus Chronic Coronary Syndrome

ObjectivesThe primary objective of the current analysis was to assess the association between the clinical presentation at index procedure and mortality in patients with second-generation drug-eluting stent thrombosis (G2-ST).BackgroundPatients with acute coronary syndrome (ACS) have a higher risk for stent thrombosis (ST) as compared with those with chronic coronary syndrome (CCS). However, clinical outcomes of patients with G2-ST after treatment for ACS and CCS remain poorly understood.MethodsFrom the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 313 patients with G2-ST. According to baseline clinical presentation, patients were divided into the 2 groups: the ACS and CCS groups (n = 147 and n = 166, respectively). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST events. Timing of ST, target lesion revascularization, and recurrent ST were also assessed.ResultsEarly ST was more frequently observed in the ACS group (71.4% vs. 44.6%), while very late ST was less likely to occur in the ACS group than in the CCS group (11.6% vs. 30.7%). Cumulative 3-year incidence of all-cause death after the index ST events was comparable between the ACS and CCS groups (28.6% vs. 28.3%; hazard ratio: 1.14; 95% confidence interval: 0.75 to 1.73; p = 0.55). Compared with the CCS group, the ACS group showed higher incidences of target lesion revascularization and recurrent ST (23.8% vs. 17.2%; p = 0.06; and 9.9% vs. 1.4%; p = 0.001, respectively).ConclusionsPatients with G2-ST were associated with higher mortality irrespective of baseline clinical presentation.     

Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity

AimsAdults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight.Data synthesisA Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46–12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12–9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02–14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17–2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15–1.64).ConclusionsAlthough we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications.Registration number (PROSPERO)CRD42020210329.     

Association of Age of Onset of Hypertension With Cardiovascular Diseases and Mortality

BackgroundThe relations of hypertension onset age with cardiovascular diseases (CVD) and all-cause mortality remain inconclusive.ObjectivesThis study sought to examine the associations of hypertension onset age with CVD and all-cause mortality.MethodsThis prospective study included 71,245 participants free of hypertension and CVD in the first survey (July 2006 to October 2007) of the Kailuan study, a prospective cohort study in Tangshan, China. All participants were followed biennially until December 31, 2017. A total of 20,221 new-onset hypertension cases were identified during follow-up. We randomly selected 1 control participant for each new-onset hypertensive participant, matching for age (±1 year) and sex, and included 19,887 case-control pairs. We used weighted Cox regression models to calculate the average hazard ratios of incident CVD and all-cause mortality across the age groups.ResultsDuring an average follow-up of 6.5 years, we identified 1,672 incident CVD cases and 2,008 deaths. After multivariate adjustment, with the increase in hypertension onset age, the hazards of outcomes were gradually attenuated. The average hazard ratio (95% confidence interval) of CVD and all-cause mortality were 2.26 (1.19 to 4.30) and 2.59 (1.32 to 5.07) for the hypertension onset age <45 years old group, 1.62 (1.24 to 2.12) and 2.12 (1.55 to 2.90) for the 45- to 54-year age group, 1.42 (1.12 to 1.79) and 1.30 (1.03 to 1.62) for the 55- to 64-year age group, and 1.33 (1.04 to 1.69) and 1.29 (1.11 to 1.51) for the ≥65-year age group, respectively (p for interaction = 0.38 for CVD and <0.01 for death).ConclusionsHypertension was associated with a higher risk for CVD and all-cause mortality, and the associations were stronger with a younger age of onset.     

Relevance of Fitness to Mortality Risk in Men Receiving Contemporary Medical Care

BackgroundAn inverse association between cardiorespiratory fitness and mortality was robustly demonstrated 3 decades ago.ObjectivesThe purpose of this study was to determine whether significant advances in disease prevention, detection, and treatment since that time have modified this association.MethodsA total of 47,862 men completed baseline examinations, including a maximal treadmill test. Cohort 1 (n = 24,475) was examined during 1971 to 1991 and followed for mortality through 1992. Cohort 2 (n = 23,387) was examined during 1992 to 2013 with follow-up through 2014. Men were categorized as low fit, moderate fit, or high fit using Cooper Clinic normative data. Hazard ratios (HRs) for all-cause, cardiovascular disease, and cancer mortality were determined across fitness categories in the 2 cohorts.ResultsA significant inverse trend between fitness categories and all-cause (HR: 1.0, 0.60, and 0.53 in cohort 1 and HR: 1.0, 0.76, and 0.52 in cohort 2) and cardiovascular disease mortality (HR: 1.0, 0.55, and 0.43 in cohort 1 and HR: 1.0, 0.84, and 0.52 in cohort 2) was observed (p trend <0.001 for all). The trend across fitness categories and cancer mortality was significant for cohort 1 (HR: 1.0, 0.62, and 0.48; p < 0.001), but not for cohort 2 (HR: 1.0, 1.08, and 0.74; p = 0.19). HRs for all-cause mortality were 0.86 (95% confidence interval: 0.82 to 0.90) and 0.87 (95% confidence interval: 0.83 to 0.91) per 1-MET increment in fitness for cohorts 1 and 2, respectively (p < 0.001 for both). Similar values were seen for cardiovascular disease and cancer mortality.ConclusionsDespite significant advances in disease prevention, detection, and treatment since fitness was first shown to be associated with mortality, the inverse association between fitness and mortality remains consistent in a contemporary cohort of men.     

Diastolic Blood Pressure and Heart Rate Are Independently Associated With Mortality in Chronic Aortic Regurgitation

BackgroundThe prognostic significance of diastolic blood pressure (DBP) and resting heart rate (RHR) in patients with hemodynamically significant aortic regurgitation (AR) is unknown.ObjectivesThis study sought to investigate the association of DBP and RHR with all-cause mortality in patients with AR.MethodsConsecutive patients with ≥ moderate to severe AR were retrospectively identified from 2006 to 2017. The association between all-cause mortality and routinely measured DBP and RHR was examined.ResultsOf 820 patients (age 59 ± 17 years; 82% men) followed for 5.5 ± 3.5 years, 104 died under medical management, and 400 underwent aortic valve surgery (AVS). Age, symptoms, left ventricular ejection fraction (LVEF), LV end-systolic diameter-index (LVESDi), DBP, and RHR were univariable predictors of all-cause mortality (all p ≤ 0.002). When adjusted for demographics, comorbidities, and surgical triggers (symptoms, LVEF, and LVESDi), baseline DBP (adjusted-hazard ratio [HR]: 0.79 [95% confidence interval: 0.66 to 0.94] per 10 mm Hg increase, p = 0.009) and baseline RHR (adjusted HR: 1.23 [95% confidence interval: 1.03 to 1.45] per 10 beat per min [bpm] increase, p = 0.01) were independently associated with all-cause mortality. These associations persisted after adjustment for presence of hypertension, medications, time-dependent AVS, and using average DBP and RHR (all p ≤ 0.02). Compared with the general population, patients with AR exhibited excess mortality (relative risk of death >1), which rose steeply in inverse proportion (p nonlinearity = 0.002) to DBP starting at 70 mm Hg and peaking at 55 mm Hg and in direct proportion to RHR starting at 60 bpm.ConclusionsIn patients with chronic hemodynamically significant AR, routinely measured DBP and RHR demonstrate a robust association with all-cause death, independent of demographics, comorbidities, guideline-based surgical triggers, presence of hypertension, and use of medications. Therefore, DBP and RHR should be integrated into comprehensive clinical decision-making for these patients.     

Left Ventricular Hypertrophy and Clinical Outcomes Over 5 Years After TAVR: An Analysis of the PARTNER Trials and Registries

ObjectivesThis study sought to evaluate the association between severity of left ventricular hypertrophy (LVH) before transcatheter aortic valve replacement (TAVR) and outcomes out to 5 years.BackgroundPrior studies assessing the association between baseline LVH and outcomes after surgical or TAVR for aortic stenosis (AS) have yielded conflicting results.MethodsPatients with severe symptomatic AS at intermediate or high risk in the PARTNER (Placement of Aortic Transcatheter Valve) 1, 2, and S3 trials and registries who received TAVR and had baseline measurements for left ventricular mass index (LVMi) were analyzed. The presence and severity of LVH was determined by LVMi using American Society of Echocardiography sex-specific cutoffs.ResultsAmong 4,280 patients, those with no (n = 1,325), mild (n = 777), moderate (n = 628), and severe (n = 1,550) LVH had 5-year rates of death of 32.8%, 37.3%, 37.2%, and 44.8%, respectively (p < 0.001), and 5-year rates of cardiovascular (CV) death or rehospitalization of 33.6%, 39.2%, 42.4%, and 49.2%, respectively (p < 0.001). After adjustment, severe LVH (compared with no LVH) was associated with increased all-cause death (adjusted hazard ratio: 1.16; 95% confidence interval: 1.00 to 1.34; p = 0.04) and CV death or rehospitalization (adjusted hazard ratio: 1.34; 95% confidence interval: 1.16 to 1.54; p < 0.001), but no increased hazard was observed for mild or moderate LVH. In spline analyses performed in males and females separately, there was a consistent linear association between increased LVMi and an increased adjusted hazard of CV mortality or rehospitalization. A similar relationship was observed for all-cause death in females, but not males.ConclusionsSevere baseline LVH is associated with higher 5-year death and rehospitalization rates after TAVR. These findings may have implications for the optimal timing of valve replacement and the potential role for medical therapy to slow or prevent LVH as AS progresses before valve replacement, but further studies are needed.