Lower Risk Of Cardiovascular Events Research Articles

#233 Marine n-3 polyunsaturated fatty acids and cardiovascular events in patients with end-stage renal disease receiving hemodialysis

Abstract Background and Aims Cardiovascular (CV) disease is the leading cause of death in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). The two major marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have cardioprotective effects. This study aimed to investigate the predictive value of plasma n-3 PUFAs on CV events and all-cause mortality in patients with ESRD receiving HD. Method A validated prospective multicenter cohort study of 336 patients with ESRD receiving HD with 5 years of follow-up was conducted. Blood samples were collected at baseline and analyzed for the plasma levels of EPA and DHA expressed as a weight percentage (wt%) of total plasma fatty acids. The primary outcome was CV events defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease (PAD), or cardiovascular mortality. The secondary outcomes were all-cause mortality and each individual component of CV events. The sum of EPA and DHA (EPA+DHA) was used in all analyses and expressed as n-3 PUFAs in wt%. The population was divided into three groups according to n-3 PUFA tertiles. Kaplan-Meier curves and multivariable Cox regressions adjusted for relevant confounders were used to analyze the association between plasma n-3 PUFA levels and study outcomes. Results Median follow-up time was 5.05 years (IQR, 5.02-5.07). Mean age was 65 ± 15 years and plasma n-3 PUFA levels ranged from 2.1 to 16.8 wt%, with a median of 5.7 wt% (IQR, 4.72-6.96 wt%). During follow-up 60% of the cohort died, 17% died of CV disease, and 42% had a CV event. Figure 1 shows the unadjusted associations between the plasma n-3 PUFA tertiles and the risk of CV events. A n-3 PUFA level between 5.06-6.52 wt% was associated with a 36% lower risk of CV events [unadjusted HR 0.64 (95% CI 0.43-0.96)]. Additionally, a n-3 PUFA level above 6.52 wt% was associated with a 34% lower risk of CV events [unadjusted HR 0.66 (95% CI 0.44-0.98)], both in comparison to levels below 5.06 wt%. After adjusting for relevant confounders, as shown in Figure 2, n-3 PUFA levels between 5.06 to 6.52 wt% were associated with a significantly lower risk of CV events [adjusted HR 0.60 (95% CI 0.40-0.92)], PAD [adjusted HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [adjusted HR 0.61 (95% CI 0.42-0.86)], when compared to levels below 5.06 wt%. Conclusion In this study of patients with ESRD receiving HD, a low plasma level of n-3 PUFA was associated with a higher risk of CV events, peripheral artery disease, and all-cause mortality.

Long-term Effects of Phosphodiesterase-5 Inhibitors on Cardiovascular Outcomes and Death: A Systematic Review and Meta-analysis.

Phosphodiesterase 5 inhibitors (PDE-5i), which are widely used for the treatment of erectile dysfunction (ED), have been found to exhibit systemic vascular benefits by improving endothelial function. In this context, we sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality. A comprehensive search of electronic databases was conducted up to May 30, 2023. Cohort studies comparing PDE5i treatment at any dose with other ED treatment, placebo or no treatment and minimum follow-up duration of 6 months were considered eligible. The primary endpoints were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. Sixteen studies were included (1,257,759 subjects - 10.5% treated with PDE5i). The majority of patients (99.4%) were men[median age 61.5 years (range 30 - 72.8)]. The median follow-up duration was 4.3 years (range 6 months - 7.5 years). PDE5i use was associated with a significant reduction in the composite of MACE (RR 0.78, 95% CI 0.69-0.89). Moreover, the analysis of pooled data from 13 studies, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.56-0.87). The use of PDE5i primarily in men with or without known coronary artery disease was associated with a lower risk for cardiovascular events and overall mortality. This information underlines that PDE5i could provide clinical benefit beyond ED treatment and could instigate the conduction of further, large-scale randomized clinical trials.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear. The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching. The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period. Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification.

Respiratory exchange ratio overshoot during exercise recovery: a promising prognostic marker in HFrEF.

Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF. This cross-sectional study includes HFrEF patients who underwent functional evaluation with maximal CPET for the heart transplant checklist at our Sports and Exercise Medicine Division. RER recovery parameters, including RER overshoot as the percentual increase of RER during recovery (RER mag), have been evaluated after CPET with assessment of hard clinical long-term endpoints (MACEs/deaths and transplant/LVAD-free survival). A total of 190 patients with HFrEF and 103 controls were included (54.6 ± 11.9years; 73% male). RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects (RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%), and they showed significant correlations with prognostically relevant CPET parameters. Thirty-three patients with HFrEF did not present a RER overshoot, showing worse cardiorespiratory fitness and efficiency when compared with those patients who showed a detectable overshoot (VO2 peak: 11.0 ± 3.1 vs 15.9 ± 5.1ml/kg/min; VE/VCO2 slope: 41.5 ± 8.7 vs 32.9 ± 7.9; ΔPETCO2: 2.75 ± 1.83 vs 4.45 ± 2.69mmHg, respectively). The presence of RER overshoot was associated with a lower risk of cardiovascular events and longer transplant-free survival. RER overshoot represents a meaningful cardiorespiratory index to monitor during exercise gas exchange evaluation; it is an easily detectable parameter that could support clinicians to comprehensively interpreting patients' functional impairment and prognosis. CPET recovery analyses should be implemented in the clinical decision-making of advanced HF.

Impact of diagnosis-to-ablation time on clinical outcomes in patients with early-onset atrial fibrillation.

Evidence was lacking for the early choice of radiofrequency ablation (RFA) among patients with early-onset atrial fibrillation (AF). This study aimed to explore whether earlier RFA was associated with better clinical outcomes among early-onset AF patients. Patients, who were diagnosed with AF before 45 years and underwent their first RFA procedures at baseline of the China Atrial Fibrillationregistry, were enrolled and divided into four diagnosis-to-ablation time (DAT) groups: DAT ≤ 1 year, 1 year < DAT ≤ 3 years, 3 years < DAT ≤ 6 years, and DAT > 6 years. Another group of nonablation patients, who were newly diagnosed with AF and younger than 45 years, were also included. Adjusted associations of groups with composite cardiovascular events (cardiovascular death, embolism, major hemorrhages, or cardiac rehospitalization) or recurrent AF were analyzed using Cox proportional hazards models. Among 1694 patients who underwent their first RFA at enrollment, incidences of composite cardiovascular outcomes were increasing with extension of DAT (DAT ≤ 1 year: 6.1/100 person-years, 1 year < DAT ≤ 3 years: 7.9/100 person-years, 3 years < DAT ≤ 6 years: 7.6/100 person-years, DAT > 6 years: 10.5/100 person-years; p < .001). In comparison with DAT > 6 years group, theDAT ≤ 1 year group was associated with reduced risk of cardiovascular events (adjusted hazard ratio, HR[95%confidence interval,CI] = 0.64 [0.47-0.87], p = .005) and AF recurrence (adjusted HR[95% CI] = 0.70 [0.57-0.88], p = .002). Associations remained similar after stratified by AF types. Compared to nonablation group (n = 413), DAT ≤ 1year patients tended to show lower cardiovascular risk (adjusted HR[95% CI] = 0.78 [0.58-1.05], p = .099) and lower risk of recurrent AF (adjusted HR[95% CI] = 0.46 [0.38-0.55], p < .001). A shorter DAT was associated with a lower risk of cardiovascular events and recurrent AF for early-onset AF patients.

Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study

BackgroundCardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort.MethodsWe conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin–angiotensin–aldosterone system inhibitors.ResultsDuring the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66–0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased.ConclusionsStatin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.

Ultra-processed food consumption and cardiovascular events risk

Abstract Background The consumption of ultra-processed food (UPF) has been suggested to be associated with cardiovascular events risk, but their dose-response relationship have not reached a consensus. Methods We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for manuscripts published from inception to November 17, 2021, which reported the relationship between UPF consumption and cardiovascular events risk. A total of ten studies were included with 325,403 participants and 38,720 cardiovascular events cases. Using the fixed/random-effects models, hazard ratios of pooled outcomes were estimated. Results A non-linear relationship of UPF consumption with cardiovascular events risk was identified (P for heterogeneity = 0.013, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.013). Compared with the lowest UPF consumption category, the third highest pooled HR for cardiovascular events risk was 1.02 (95% CI, 0.98 to 1.05), the second highest was 1.08 (95% CI, 1.04 to 1.12) and the highest was 1.24 (95% CI, 1.16 to 1.32). A linear association between UPF consumption and coronary heart disease (CHD) risk was identified (P for heterogeneity = 0.110, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.202). A 10% increase in UPF consumption in daily calorie intake was associated with a 6% increase in CHD risk. UPF consumption was non-linearly associated with cerebrovascular disease (CeVD) risk (P for heterogeneity = 0.001, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.026). Conclusions There was a nonlinear relationship between UPF consumption and cardiovascular events. Moderate intake of UPF was associated with a lower risk of cardiovascular events, with the lowest risk at &amp;lt;15%/day of UPF consumption out of total calorie intake. Heavy UPF consumption was significantly and positively associated with increased risk of cardiovascular events.

Effect of renin-angiotensin system inhibitors on cardiovascular events in hemodialysis patients with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

The clinical benefits of renin-angiotensin system inhibitors (RASi) in patients undergoing hemodialysis remain obscure. This is a post hoc cohort analysis of the LANDMARK trial investigate whether RASi use was associated with cardiovascular events (CVEs) and all-cause mortality. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity-score matching. The risk of CVEs was similar between participants with RASi use at baseline and those without RASi use at baseline and between participants with RASi use during the study period and those without RASi use during the study period. No clinical benefits of RASi use on all-cause mortality were observed. Serum phosphate levels were significantly associated with the effect of RASi on CVEs. RASi use was not significantly associated with a lower risk of CVEs or all-cause mortality in hemodialysis patients at risk of vascular calcification.

Long-term Clinical Outcomes Following Cardiac Stress Testing After Percutaneous Coronary Intervention.

Cardiac stress testing (CST) is commonly performed after percutaneous coronary intervention (PCI), yet little is known whether such ischemic testing is associated with improved clinical outcomes. We studied patients who underwent their first PCI procedure from October 2008 to December 2016 in Ontario, Canada. Patients who underwent CST from 60 days to 1 year after PCI were compared with those who did not undergo CST. The primary outcome was a composite of cardiovascular death or hospitalisation for myocardial infarction (MI) at 3 years after CST. Inverse probability of treatment weighting was used to adjust for potential differences between the study groups. Among the 86,150 included patients, 40,988 (47.6%) underwent CST within 60 days to 1 year after PCI. Patients who underwent CST had higher prescription rates of cardiac medications. At 1 year after CST, rates of cardiac catheterisation and coronary revascularisation were more than double those observed in the nontested group (13.4% vs 5.9%, standardised difference [SD] 0.26, for cardiac catheterisation; 6.6% vs 2.7%, SD 0.19, for PCI). The CST group had a significantly lower primary event rate at 3 years compared without CST (3.9% vs 4.5%, hazard ratio 0.87, 95% confidence interval 0.81-0.93). This population-based study of PCI patients found a small but significantly lower risk of cardiovascular events among patients who received CST. Further studies are needed to confirm these findings and determine the specific aspects of care that may be associated with the modestly improved outcomes.

Association of Vascular Aging With Cardiovascular Disease in Middle-Aged Chinese People: A Prospective Cohort Study

BackgroundWhether middle-aged individuals with a greater difference between chronological age and vascular age show a lower cardiovascular disease risk remains to be clarified. ObjectivesThis study sought to examine whether individuals with supernormal vascular aging (VA) have a lower cardiovascular disease risk than do individuals with normal VA. MethodsThis prospective cohort study included 20,917 middle-aged (40-60 years) participants from the Kailuan Study. VA was defined as the predicted age in a multivariate regression model, including classic cardiovascular risk factors and pulsed wave velocity. The chronological age minus the VA was defined as the Δ-age, and the 10th and 90th percentiles of the Δ-age were used as cutoffs to define early VA and supernormal VA, respectively. The outcome was a composite of myocardial infarction, hospital admission for heart failure, and stroke. The study used Cox proportional hazards regression to examine the association between the VA categories and the incident cardiovascular outcome. ResultsDuring the median 4.6-year follow-up period, 584 endpoint events were observed. After adjusting for potential variables, when compared with the normal VA group, the supernormal VA group had a decreased rate of cardiovascular events (HR: 0.47; 95% CI: 0.35-0.64), and the early VA group had an increased rate (HR: 1.90; 95% CI: 1.22-2.95) of cardiovascular events. ConclusionsIndividuals with supernormal VA are at a lower risk of cardiovascular events, and individuals with early VA are at a higher risk of cardiovascular events than individuals with normal VA. Further characterization may provide novel insight into future preventive strategies against cardiovascular disease.

Incremental Benefit of Lipid Lowering in a Large Chinese Population Aged 75 Years and Older With Established Atherosclerotic Cardiovascular Disease

ObjectiveTo explore the optimal low-density lipoprotein cholesterol (LDL-C) level in patients aged 75 years and older with established atherosclerotic cardiovascular disease (ASCVD). Patients and MethodsWe conducted a retrospective multicenter cohort study of veterans aged 75 years and older with ASCVD who were regularly hospitalized or medically examined in 15 medical institutions in southern China from January 1, 2006, to December 31, 2013. Follow-up continued through October 1, 2021. The time-weighted average (TWA) LDL-C level represented the average LDL-C level during follow-up. Participants were divided into TWA LDL-C groups of 55.0 mg/dL or lower, 55.1 to 70.0 mg/dL, 70.1 to 85.0 mg/dL, 85.1 to 100.0 mg/dL, and greater than 100.0 mg/dL. The subgroup with LDL-C levels lower than 55.0 mg/dL was further subdivided into groups with LDL-C levels from 40.1 to 55.0 mg/dL and 40.0 mg/dL or less. The association of TWA LDL-C levels with outcomes was evaluated with Cox proportional hazards models. ResultsOverall, 6387 patients aged 75 years or older with ASCVD were included (mean age, 79.4 years). In total, 4267 major adverse cardiovascular events, 1518 stroke events, and 515 myocardial infarction events occurred during a mean follow-up of 12.7 years. Generally, lower TWA LDL-C level was associated with a lower risk of cardiovascular events but was not associated with a higher risk of adverse events in elderly individuals with ASCVD, with the lowest cardiovascular risk observed for LDL-C levels of less than 55.0 mg/dL. After multivariable adjustment, the risk of a major adverse cardiovascular event was 1.30 (95% CI, 1.26 to 1.34; P<.001) for a per SD increment in TWA LDL-C level. Compared with TWA LDL-C levels of 40.1 to 55.0 mg/dL, TWA LDL-C levels of 40.0 mg/dL or less were associated with an increased risk of hemorrhagic stroke (hazard ratio, 3.71; 95% CI, 1.89 to 7.26). ConclusionLow-density lipoprotein cholesterol levels from 40.1 to 55.0 mg/dL exhibited the maximum cardiovascular benefit in patients aged 75 years and older who had ASCVD. Lowering LDL-C levels to 40.0 mg/dL or less might increase the risk of hemorrhagic stroke.

Association of prior outpatient diabetes screening with cardiovascular events and mortality among people with incident diabetes: a population-based cohort study

BackgroundOutcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada.MethodsWe conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014–2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death.ResultsWe included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63–0.69) and mortality (0.68, 0.64–0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77–0.88) and mortality (0.71, 0.66–0.78) outcomes than a result in the normoglycemic range.ConclusionsPreviously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults.

Statin Treatment on Cardiovascular Risk After Retinal Artery Occlusion: A Historical Cohort Study

IntroductionRetinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events.MethodsThis study was a historical cohort study with nested case–control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed.ResultsAmong 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520–0.780; P < 0.001). A longer duration of statin exposure was associated with a lower cardiovascular risk.ConclusionsIn patients with newly diagnosed RAO, treatment with statins, particularly long-term use, was associated with a low risk of future cardiovascular events.

Efficacy of the calcium channel blocker amlodipine in the treatment of salt-sensitive hypertension in patients with different genetic status

Aim. To study the effectiveness of the calcium channel blocker amlodipine in the treatment of salt-sensitive hypertension (HTN) and compare it with the genotypes of patients.Material and methods. The study involved 96 patients aged 42,7±5,2 years. There were following inclusion criteria: diagnosis — grade 1, stage 1 hypertension with low risk of cardiovascular events (CVEs). Before inclusion in the study, patients had not taken regular antihypertensive therapy for 3 months. Next, all patients underwent assessment of salt sensitivity of blood pressure according to the M. H. Weinberger method and, based on it, the participants were divided into salt-sensitive and salt-resistant. Regardless of the result, all patients were recommended to have a low-salt diet of 3-5 g/day, with subsequent 24-hour ambulatory blood pressure monitoring (ABPM) during the diet. In patients with ineffective diet, amlodipine was prescribed on day 26 at a dose of 2,5-5 mg once a day. The effectiveness of the drug was assessed by repeated ABPM. In addition, a genetic study was performed on 4 polymorphic variants of the genes AGT (T704C), AGT (C521T), AGTR1 (A1166C), AGTR2 (G1675A), ADD1 (G1378T), CYP11B2 (C344T), GNB3 (C825T), NOS3 (T786C), NOS3 (G894T), to determine their association with the effectiveness of a low-salt diet and amplodipine therapy.Results. In patients with grade 1, stage 1 hypertension with low risk of CVEs, the effectiveness of a low-salt diet and amlodipine monotherapy at a dose of 2,55 mg/day was revealed. The results of the study were confirmed by achieving target values of office blood pressure and ABPM. In hypertensive patients not sensitive to salt, amlodipine monotherapy was ineffective. The genotyping revealed a relationship between antihypertensive therapy with amlodipine in salt-sensitive patients and carriage of the GG polymorphism of the AGTR2 gene.Conclusion. The effectiveness of amlodipine and a low-salt diet in salt-sensitive patients with grade 1 hypertension, stage 1, low risk of CVEs with carriage of the GG genotype of the AGTR2 gene.

Association between physical activity and clinical outcomes in high-risk hypertension: Post-hoc analysis of SPRINT

ObjectiveEngaging in physical activity (PA) is recommended to reduce the risk of morbidity and mortality in patients with hypertension. However, the association between PA and clinical outcomes in individuals with high-risk hypertension is understudied. We examined the relationship between PA and clinical outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT investigated the benefit of intensive (vs. standard) blood pressure treatment in patients with high-risk hypertension. MethodsBaseline data on PA was self-reported. Vigorous-intensity PA (VPA) was categorized into 2 groups based on frequency of “Rarely or Never” and 1 or more sessions/month. Moderate-intensity PA (MPA) was also categorized into 2 groups based on average duration/day of <15 min and 15 or more minutes. Using multivariable Cox regression, we estimated the associations between PA the primary outcome which was a composite of cardiovascular events, and all-cause mortality. ResultsA total of 8,320 (age 67.8 ± 9.3, 34.9% women) of SPRINT participants with data on PA were included. During a median follow-up of 3.8 years, 619 primary outcome, and 419 all-cause mortality events occurred. Compared to not engaging in VPA, the risk of the primary outcome, myocardial infarction, and all-cause mortality (HR 95% CIs) associated with VPA of ≥1sessions/month was 0.79(0.65–0.94; p=0.009), 0.70(0.52–0.93; p=0.014) and 0.75(0.60–0.94; p=0.011), respectively. Similarly, the risk of the primary outcome and all-cause mortality (HR 95% CI) associated with engaging in MPA for ≥15 min/day, relative to <15 min/day was 0.76(0.63–0.93; p=0.008) and 0.80(0.62–1.02; p=0.066), respectively. ConclusionAmong individuals with hypertension from the SPRINT study, VPA and MPA at a threshold of ≥1sessions/month and MPA of ≥15 min/day respectively, were both associated with a lower risk for cardiovascular events, and VPA was also associated with a reduced risk for all-cause mortality. Further studies are required to identify the optimal volume and intensity of PA in high-risk hypertension.

Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation.

Background Whether the early use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose-lowering drugs were matched based on a propensity score. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all-cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow-up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54-0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60-0.99]; P=0.04). All-cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all-cause mortality, hospitalizations for heart failure, and major adverse cardiac events.

Antithrombotic Therapy in Chronic Kidney Disease

Abstract Chronic kidney disease (CKD) affects over 10% of the global population and is more prevalent in the elderly, females, patients with diabetes or hypertension, and certain racial minorities. CKD is a leading cause of mortality, especially in CKD stage G5 and End-Stage Renal Disease (ESRD). Left ventricular hypertrophy (LVH) is common in CKD patients, predicting mortality even in early stages. CKD patients face a higher risk of bleeding, with a 3.5 times higher risk in hemodialysis patients. Atrial fibrillation (AF) and acute coronary syndrome are more prevalent in patients with eGFR &lt;60 ml/min, and the risk of pulmonary embolism increases by 25-30% regardless of CKD stage. Antithrombotic treatment is crucial for CKD patients with cardiovascular diseases. In early stages (G1-G3), both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) can be used, with NOACs preferred due to their safety profile. In advanced stages (G4-G5) and ESRD (G5D), warfarin is commonly used, with reduced NOAC doses as an option. NOACs require careful monitoring of renal function, and hemodialysis can remove a significant portion of plasma dabigatran. Monitoring renal function is vital for CKD patients receiving NOACs. Some studies suggest NOACs may have a lower risk of cardiovascular events compared to warfarin, but conflicting data exist regarding bleeding risk. Individualized treatment decisions should consider the patient's renal function.

The effect of dapagliflozin therapy on ventricular repolarization parameters in electrocardiography in patients with diabetic cardiovascular disease

BackgroundDapagliflozin is an agent that has both antihyperglycemic effects and is significantly associated with a lower risk of cardiovascular events in patients with diabetes mellitus (DM). However, there is insufficient data and information about the effect of dapagliflozin on electrocardiographic (ECG) parameters. AimThe effects of dapagliflozin on ventricular repolarization parameters have not been fully elucidated yet. This study aimed to investigate whether dapagliflozin has a positive effect on ventricular repolarization heterogeneity parameters in patients with type 2 DM. MethodWe retrospectively enrolled 140 patients with a known diagnosis of type 2 DM who were newly prescribed dapagliflozin in addition to standard anti-diabetic therapy. The patients were divided into two groups according to whether they had cardiovascular disease (CVD). The effect of dapagliflozin treatment on ventricular repolarization parameters (frontal plane QRST angle, Tp-e interval, Tp-e/QTc, QTc, and QTc dispersion) was investigated, patient groups were compared before and after treatment. ResultsAmong 140 patients, 70 (50 %) had CVD and 70 (50 %) did not have CVD. Dapagliflozin treatment resulted in significant reductions in ventricular repolarization parameters over the study period in the CVD group with diabetes. Mean fQRST angle, Tp-e interval, Tp-e/QTc, QTc, and QTc dispersion were significantly lower than baseline values at 6-month follow-up visits in the CVD group (61.61 ± 9.22° vs 52.55 ± 8.31°, 74.45 ± 16.06 msec vs 63.27 ± 13.99 msec, 0.19 ± 0.03 vs 0.16 ± 0.03, 384.12 ± 47.93 msec vs 356.15 ± 43.31 mesc, 55.28 ± 5.50 msec vs 48.08 ± 6.48 msec for all pairwise comparisons p < 0.001). ConclusionSimilar antihyperglycemic effects were found with dapagliflozin treatment in patients with and without CVD. However, significant reductions in ventricular repolarization parameters were observed only in patients with CVD.

THE RENIN ANGIOTENSIN SYSTEM BLOCKADE DOES NOT SIGNIFICANTLY REDUCE THE RISK OF CARDIOVASCULAR EVENTS IN DIALYSIS PATIENTS: A META-ANALYSIS OF 5 RCTS

Objective: Angiotensin-converting-enzyme-inhibitors (ACEIs) and/or angiotensin-receptor-blockers (ARBs) are recommended by guidelines as first-line therapies for the management of hypertension in the general population. However, the cardioprotective benefit of these agents among patients on chronic dialysis remains uncertain. This meta-analysis aimed to explore the effect of ACEIs/ARBs on cardiovascular events in this high-risk patient population. Design and method: We searched Medline/PubMed and Cochrane database of clinical trials from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the effect of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis. RCTs were eligible in quantitative data synthesis, if they were assessing fatal or non-fatal cardiovascular events as a primary efficacy endpoint. Results: We identified 5 RCTs including a total of 1,582 dialysis patients. As compared with placebo or no add-on treatment, the use of ACEIs/ARBs was not associated with a significantly lower risk of cardiovascular events [risk ratio (RR): 0.79; 95% confidence interval (CI): 0.57-1.11; I2 = 73%, P = 0.005]. Furthermore, there was no benefit of ACEIs/ARBs on cardiovascular mortality (RR: 0.82; 95% CI: 0.59-1.14; I2 = 6%, P = 0.37) and all-cause mortality (RR: 0.86; 95% CI: 0.64-1.15; I2 = 44%, P = 0.13). These results were consistent, when the included RCTs were stratified into subgroups according to the hypertension status and ethnicity of patients, sample size, duration of follow-up and method quality. Conclusions: The present meta-analysis showed that among patients on dialysis, the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality as compared with placebo or no add-on treatment.

Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events.

Transforming growth factor-beta (TGF-β) exists in three isoforms TGF-β1, -β2 and -β3. TGF-β1 has been suggested to be important for maintaining plaque stability, yet the role of TGF-β2 and -β3 in atherosclerosis remains to be investigated. This study explores the association of these three isoforms of TGF-β with plaque stability in the human atherosclerotic disease. TGF-β1, -β2 and -β3 proteins were quantified in 223 human carotid plaques by immunoassays. Indications for the endarterectomy were: symptomatic carotid plaque with stenosis >70% or without symptoms and >80% stenosis. Plaque mRNA levels were assessed by RNA sequencing. Plaque components and extracellular matrix were measured histologically and biochemically. Matrix metalloproteinases were measured with ELISA. Monocyte chemoattractant protein-1 (MCP-1) was measured with immunoassays. The effect of TGF-β2 on inflammation and protease activity was investigated in vitro using THP-1 and RAW264.7 macrophages. Patients were followed longitudinally for cardiovascular events.TGF-β2 was the most abundant isoform and was increased at both protein and mRNA levels in asymptomatic plaques. TGF-β2 was the main determinant separating asymptomatic plaques in an Orthogonal Projections to Latent Structures Discriminant Analysis. TGF-β2 correlated positively to features of plaque stability and inversely to markers of plaque vulnerability. TGF-β2 was the only isoform inversely correlated to the matrix-degrading matrix metalloproteinase-9 and inflammation in the plaque tissue. In vitro, TGF-β2 pre-treatment reduced MCP-1 gene and protein levels as well as matrix metalloproteinase-9 gene levels and activity. Patients with plaques with high TGF-β2 levels had a lower risk to suffer from future cardiovascular events. TGF-β2 is the most abundant TGF-β isoform in human plaques and may maintain plaque stability by decreasing inflammation and matrix degradation.