Composite Of Major Cardiovascular Events Research Articles

Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease

BackgroundClassical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD.MethodTwo hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE).ResultsThe median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates).ConclusionOur results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Lipoprotein(a) and cardiovascular prognosis of familial dyslipidemias: data from a 10-year follow-up study

Abstract Background Familial dyslipidemias, such as heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) are associated with premature cardiovascular (CV) disease. On the other hand, increased lipoprotein(a) [Lp(a)] is considered as the most prevalent monogenic lipid disorder in the general population. Purpose This study aimed to longitudinally follow up two specific populations with familial dyslipidemias associated with increased CV risk, namely FH and FCH, and compare them with reference to their CV prognosis, investigating in parallel the effect of Lp(a) levels. Methods 433 patients with FH (34% males, mean age 44.2±12.8 years) and 476 patients with FCH (57% males, mean age 49.0±11.1 years) from the outpatient lipid clinic of our hospital, without history of CV disease, who fulfilled the FH and FCH criteria, respectively, participated in the study. Participants were evaluated for a mean follow-up period of 9.6±7.6 years, with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke). Results The incidence of the composite endpoint of major CV events during the follow-up period in the total population was 6.5%, while it was greater in patients with FH compared to patients with FCH (8.1% vs 5.5%, p=0.03). Regarding CV risk factors, FCH compared to FH patients had greater prevalence of baseline hypertension (36% vs 9.7%, p<0.001) and diabetes (11% vs 2%, p<0.001), whereas FH patients had greater Lp(a) levels (37.4±40.3 vs 29.7±34.6 mg/dl, p<0.01). Multiple Cox regression analysis revealed that FH patients had greater CV risk compared to FCH patients (HR 2.17, 95% CI 1.10-4.26, p=0.02). Moreover, in FH patients, increased baseline Lp(a) levels (≥30mg/dl) were an independent predictor of major adverse CV events (HR 2.37 95% CI 1.41-4.90, p=0.02), whereas in FCH patients increased Lp(a) was not an independent predictor. In FCH patients the presence of diabetes at baseline was a strong independent prognosticator of adverse CV events (HR 3.56 95% CI 1.19-11.33, p=0.03), after adjustment for confounding factors. Conclusions FH patients have greater CV risk compared to FCH patients. In FH patients, the presence of increased Lp(a) doubles the CV risk, beyond low density lipoprotein cholesterol levels. On the other hand, in FCH patients the presence of diabetes triples the CV risk, whereas Lp(a) does not convey an independent prognostic value.

Long-Term Outcomes of Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction: A Study from Mexico City

While primary percutaneous coronary intervention (pPCI) is the treatment of choice in ST elevation myocardial infarction (STEMI), challenges may arise in accessing this intervention for certain geodemographic groups. Pharmacoinvasive strategy (PIs) has demonstrated comparable outcomes when delays in pPCI are anticipated, but real-world data on long-term outcomes are limited. The aim of the present study was to compare long-term outcomes among real world patients with STEMI undergoing either PIs or pPCI. This was a prospective registry including patients with STEMI who received reperfusion during the first 12 hours from symptom onset. The primary objective was cardiovascular mortality at 12 months according the reperfusion strategy (pPCI vs PIs); major cardiovascular events (cardiogenic shock, recurrent MI, congestive heart failure) and BARC type 3-5 bleeding events were also evaluated.A total of 799 patients with STEMI were included, 49.1% underwent pPCI and 50.9% received PIs. Patients in the PIs group presented with more heart failure on admission (Killip Kimbal >I 48.1 vs 39.7, p=0.02) and had a lower proportion of pre-existing heart failure (0.2 vs 1.8%, p=0.02) and atrial fibrillation (0.25 vs 1.2%, p=0.02). No statistically significant difference was observed in cardiovascular mortality at the 12-month follow-up (HR for PIs: 0.74, 95% CI: 0.42-1.30; log-rank p=0.30) according to the reperfusion strategy employed. The composite of major cardiovascular events (HR for PIs 0.98, 95% CI: 0.75-1.29, p=0.92) as well as BARC 3-5 bleeding rates were also comparable. A low socioeconomic status, Killip-Kimball >2, age > 60 years and admission creatinine >2.0mg/dL were predictors of the composite endpoint after multivariate analysis.In conclusion, this prospective real-world registry provides additional support that long term major cardiovascular outcomes and bleeding are not different between patients undergoing PIs versus primary PCI.

Glucagon-like Peptide 1 Receptor Agonists and Cardiovascular Outcomes in Solid Organ Transplant Recipients With Diabetes Mellitus.

Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers. The primary outcome was a composite of major cardiovascular events (MACEs): a nonfatal cardiac event (myocardial infarction, stable/unstable angina, coronary bypass, and coronary angiography), ischemic stroke and all-cause mortality. Secondary outcomes were MACE or peripheral vascular disease (MACE-PVD), and all-cause mortality. Safety outcomes included biliopancreatic adverse events. We included 318 patients (69% males, average age 58.3 ± 11.0 y) with a 3.1-y median follow-up. The incidence of MACE was 101 of 1000 patient-years in GLP1-RAs users compared with 134 of 1000 in controls (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.27-0.78). GLP1-RAs similarly reduced the risk of MACE-PVD (HR 0.53; 95% CI, 0.33-0.88) and the risk of all-cause mortality (HR 0.39; 95% CI, 0.18-0.84). Biliopancreatic adverse events occurred less in GLP1-RA users. Transplant recipients with diabetes who used GLP1-RAs had lower risks for MACE and all-cause mortality. These results may profoundly implicate the daily management of posttransplant recipients with diabetes, a population with a high prevalence of cardiometabolic risk factors and cardiovascular death. Transplant patients are usually excluded from randomized controlled trials and, hence might be undertreated with disease-modifying drugs. Larger prospective studies are needed in this unique population.

Sex Differences in Cardiovascular Disease Risk Factor Prevalence, Morbidity, and Mortality in Colombia: Findings from the Prospective Urban Rural Epidemiology (PURE) Study.

Controversies exist on whether the presence of cardiovascular risk factors and their association with major cardiovascular events (MACE) is different between men and women. Most of the evidence comes from high-income countries, hindering extrapolation of sociocultural and demographic factors of other regions. To evaluate sex differences in the prevalence of cardiovascular risk factors and the incidence of MACE and diabetes in Colombian adults. We performed a survival analysis from women and men aged 35-70 belonging to the Prospective Urban Rural Epidemiology-Colombia prospective study. Incidence rates for MACE composite (myocardial infarction, stroke, heart failure, death) and each outcome and diabetes were calculated. Kaplan-Meier curves and log-rank tests were performed. The association between demographic, behavioral, and metabolic variables with MACE and diabetes were evaluated with Cox proportional hazards models. 7,552 participants (50±9.7 years) were included; 64% were women. Women had higher hypertension prevalence, body mass index, levels of total cholesterol, LDL-c, and HDL-c but lower triglycerides levels. Women were more sedentary but fewer smokers or active alcohol consumers and had higher educational levels. After 12-year mean follow-up (SD 2.3), the incidence rate of MACE composite was higher in men [4.2 (3.6-4.9) vs. 3.2 (2.8-3.7) cases per 1000 person-years]. Diabetes had the greatest association with MACE (HR = 2.63 95%CI:1.85;3.76), followed by hypertension (HR = 1.75 95%CI:1.30;2.35), low relative grip strength (HR = 1.53 95%CI:1.15;2.02), smoking (HR = 1.47 95%CI: 1.11;1.93), low physical activity (HR = 1.42 95%CI: 1.03;1.96). When evaluating risk factors by sex, only an increased waist-to-hip ratio was more strongly associated with MACE in men (p-interaction <0.05). The composite MACE outcome was higher in men despite having a lower overall burden of risk factors. The risk factors contribution was similar, leading us to reconsider the need to carrying out differentiated cardiovascular risk prevention and management campaigns, at least in our region.

Increased Lipoprotein (a) and familial hypercholesterolemia: a dangerous combination.Data from a 12-year follow-up study

Abstract Background Lipoprotein (a)[Lp(a)] is a molecule characterized by very increased atherogenicity. Mounting evidence support the causal link between high Lp(a) concentration and atherosclerotic cardiovascular (CV) disease in the general population. Purpose The role of Lp (a) in specific categories of patients at high CV risk, such as patients with familial hypercholesterolaemia (FH), is also of special importance. The aim of our study was to investigate the prognostic role of Lp (a) regarding major adverse CV outcomes in subjects with heterozygous FH. Methods 155 patients from the outpatient lipid clinic of our hospital (56 males,mean age 41.2±14.2 years, 26% smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FH criteria participated in the study. Participants were evaluated for a mean follow-up period of 12.4±7.1 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke). Results The incidence of the composite endpoint of major CV events during the follow-up period was 9% (n=14). In the total population, the mean baseline Lp (a) levels were 34.9±33.7 mg/dl, while 42% had increased Lp (a) levels ≥30mg/dl. The group of FH patients with new-onset CV disease had higher levels of Lp(a) at baseline compared to those without new-onset CV disease (48.1±37.3 vs 33.6±33.1 mg/dl, p=0.01). Also, those with new-onset CV disease had higher percentage of increased Lp(a) levels (≥30mg/dl) at baseline compared to those without development of CV disease (71% vs 39%, p=0.02).Multiple Cox regression analysis revealed that during the follow-up period independent predictors of major adverse CV events were:increased baseline Lp(a) levels(≥30mg/dl)(HR 5.61, 95% CI 1.51-10.92, p=0.01), male sex (HR 8.11, 95% CI 2.02-12.48, p&amp;lt;0.01), baseline low-density cholesterol levels (HR 1.01, 95% CI 1.00-1.02, p=0.04) and the presence of hypertension at baseline (HR 3.59, 95% CI 1.03-12.49, p=0.04), after adjustment for confounding factors. Conclusions In patients with FH, increased baseline Lp(a) is an independent predictor of adverse CV events, after a 12-year follow-up period. FH patients with Lp (a)levels ≥30mg/dl have an almost 5-fold greater CV risk compared to those with lower Lp (a) levels. It seems that Lp (a) reclassifies the already increased CV risk of FH subjects into an even higher level.

The new score predicts 1-year poor outcome in patients with successful percutaneous coronary intervention: Naples prognostic score

Aims: This study investigated the relationship between Naples prognostic score (NPS) and 1-year poor clinical outcomes in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI).&#x0D; Methods: The study included 121 patients who had NSTEMI and received successful PCI treatment. The researchers calculated NPS using the neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, serum albumin level, and total cholesterol. The patients were divided into two groups based on their NPS scores: those with scores of 0.1 and 2 and those with scores of 3 and 4. The study compared the occurrence of major cardiovascular events (MACE) such as 1-year all-cause mortality, 1-year nonfatal recurrent MI, and stroke between the two groups.&#x0D; Results: Patients with high NPS scores were observed to have significantly higher all-cause mortality than those with low NPS scores (23.9% vs. 9.3%, p=0.029). When the MACEs of the patients were compared, significantly higher MACE was observed in the high NPS group (39.1% vs. 18.7%, p=0.013).&#x0D; In multivariate logistic regression analysis, creatinine (OR:4,914, CI 95%: 1.310-18,433, p=0.018) and NPS 3-4 (OR:2.565, CI 95%: 1.093-6.017, p=0.030) were independent predictors of MACE.&#x0D; Conclusion: Composite MACEs of non-fatal recurrent MI, cerebrovascular accident, and all-cause death were higher at one year in patients with high NPS who underwent successful percutaneous intervention. High NPS is an indicator of MACE.

Left ventricular myocardial work for the prediction of postoperative outcomes in patients with bicuspid aortic stenosis.

Chronic elevation of left ventricular (LV) afterload contributes to adverse LV remodeling and myocardial impairment in bicuspid aortic valve (BAV) patients with severe aortic stenosis (AS). Incorporating LV afterload into global longitudinal strain (GLS) analysis, myocardial work facilitates early detection of LV dysfunction. The present study was to evaluate myocardial work in BAV patients with severe AS undergoing surgical aortic valve replacement (SAVR) and to evaluate its prognostic impact on early postoperative outcomes. Between January 2021 and March 2022, BAV patients with severe AS scheduled for SAVR were included and underwent comprehensive transthoracic echocardiography. Quantification of LV myocardial work was performed to obtain LV global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Clinical outcome was defined as a composite of major cardiovascular events including mortality, myocardial infarction, stroke, acute kidney injury, low cardiac output syndrome and vascular complications during hospitalization or within 30 days after operation. Among 103 BAV patients with severe AS undergoing SAVR (mean age of 65 ± 9 years, 57.3% male), 22 experienced postoperative major cardiovascular events. BAV patients with major cardiovascular events demonstrated lower LV GWI (P < 0.001) and GCW (P = 0.002) along with elder age (P = 0.030), decreased LVGLS (P = 0.026) and right ventricular longitudinal strain (P = 0.019), and higher prevalence of abnormal average E/e' ratio (P = 0.029) than those without major events. Decreased LV GWI and GCW was independently associated with the occurrence of major cardiovascular events (P < 0.01 for adjusted OR). Multivariable logistic regression model including LV GWI demonstrated superior power than the model including LVGLS and yielded best discrimination for BAV patients with and without major cardiovascular events during early postoperative period. Echocardiography-based LV myocardial work overcomes the limitations of LVGLS and presents as a promising novel index for the early detection of functional myocardial damage and the optimization of intervention timing among BAV patients with severe AS.

#2889 CAROTID PLAQUE THICKNESS PREDICTS CARDIOVASCULAR EVENTS AND DEATH IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Classical risk scoring systems highly underestimate the elevated risk of cardiovascular (CV) disease in chronic kidney disease (CKD) (1). Coronary artery calcification score (CACS) has improved prediction of CV events in patients with CKD (2). Recently, ultrasound examination of the carotid arteries with measurement of maximal carotid plaque thickness (cPTmax) has demonstrated similar predictive value as CACS in the general population (3). This is the first study to investigate whether cPTmax can predict CV events in patients with CKD. We also compared the predictive value of cPTmax and CACS. Method Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries in 2016 to 2017. The assessment consisted of finding areas with plaque, if there were any, and measuring the thickest part of the plaque, cPTmax, defined as the radial distance from the media–adventitia interface to the intima–lumen interface towards the center of the arterial lumen. For the statistical analysis only the anatomical side with the highest cPTmax was used. The intra-observer coefficient of variation was 9%. Based on the distribution of cPTmax, the subjects were divided into 3 groups: No plaques, cPTmax 1.0-1.9 mm and cPTmax &amp;gt; 1.9 mm (the median cPTmax in the group was 1.9 mm). One hundred and seventy-five of the patients underwent a non-contrast CT scan of the coronary arteries, which was used to measure CACS. The patients were divided into the following categories: no calcification, CACS = 1-100, CACS = 101-400 and CACS &amp;gt; 400. The follow-up time was time elapsed from the ultrasound scan and until a predefined end-date or the time of first event, which was defined as a composite of major CV events or death of any cause (MACE). CV events included: myocardial infarction, percutaneous coronary intervention, coronary bypass surgery, ischemic stroke, carotid endarterectomy or stenting, non-traumatic lower limb amputation, lower limb artery bypass graft, percutaneous transluminal angioplasty of a lower limb. Results The average follow-up time was 5.4 years. Twenty patients (10%) experienced a CV event and 28 patients died (14%). In a crude absolute risk plot (Figure), patients with no plaque at baseline showed the lowest risk of MACE, whereas patients with cPTmax 1.0-1.9 mm showed an intermediate risk, and patients with cPTmax &amp;gt;1.9 mm the highest risk (log rank test, p&amp;lt;0.0001). When using the group of patients with no plaque as the reference in an unadjusted Cox-regression analysis, the hazard ratio (HR) of MACE was significantly increased in patients with cPTmax = 1.0-1.9 mm (HR = 3.8 (CI: 1.5 - 9.9), p&amp;lt;0.01) and in patients with cPTmax &amp;gt;1.9 mm (HR = 8.4 (CI: 3.4 – 20.8), p&amp;lt;0.0001). After adjustment for age, sex, diabetes, smoking, hypertension, and hypercholesterolemia, only patients with cPTmax &amp;gt;1.9 mm showed a significantly increased HR of MACE (HR 3.2, CI 1.1-9.3), p&amp;lt;0.05. We applied C-statistics to assess which imaging technique had the best predictive value of MACE in this cohort. The differences in C-statistics were similar for the two imaging methods: cPTmax (0.21, p &amp;lt; 0.0001) and CACS (0.21, p &amp;lt; 0.0001). Conclusion Our results indicate that measurement of cPTmax may be a useful method for prediction of MACE in CKD. In the present small study, cPTmax and CACS showed equal potential for predicting MACE Ultrasound imaging is more convenient, more widely available, and without radiation exposure. To further assess the value of cPTmax in predicting CV risk in CKD, a larger study of patients with all CKD stages is needed.

COMPARATIVE EFFICACY AND ACCEPTABILITY OF ANTIHYPERTENSIVE DRUG CLASS COMBINATIONS FOR CARDIOVASCULAR DISEASE PREVENTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Objective: European guidelines recommend combination therapy for most hypertensive patients, but direct comparisons between major drug class combinations are lacking. Our aim was to compare the efficacy and acceptability of different drug class combinations. Design and method: We performed a systematic review and network meta-analysis guided by the recommendations from the Cochrane collaboration. We included all trials assessing any antihypertensive drug combination against another combination, single agent or placebo, with at least 1000 patient-years of follow-up in each treatment arm. Risk of bias was assessed using Cochrane Collaborations RoB2 tool, excluding trials at high risk of bias from the analysis. Odds ratios from individual trials were pooled using random-effects network meta-analysis, with composite major cardiovascular events as the primary outcome for efficacy, and treatment discontinuation as the primary outcome for acceptability. Results: 85 trials, including 406 067 participants followed for an average of 4.0 years, were included in the analysis. Mean age was 64.0 years and 41% percent were women. Overall, 15 different drug classes, drug class combinations and placebo were included in the network. Direct comparisons between dug class combinations were sparse, and there were signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Combination therapy using renin-angiotensin system inhibitors (RASi) and calcium channel blockers (CCB) appeared most effective in preventing major cardiovascular events, followed by a combination of thiazide and potassium-sparring diuretics. The combination of RASi and diuretics appeared least effective among combinations studied. For acceptability, no combination differed significantly compared to placebo, although combinations including an angiotensin receptor blocker (ARB) trended towards being more acceptable, and combinations including and angiotensin-converting enzyme inhibitor trended towards being less acceptable, compared to placebo. Conclusions: In this first network meta-analysis of antihypertensive drug combinations, RASi + CCB appears most effective in preventing major cardiovascular events. Based on a more beneficial acceptability profile, combinations including ARB may be preferred over combinations including ACEi, although these findings should be interpreted with caution due to lack of direct comparisons.

COMPARATIVE EFFICACY AND ACCEPTABILITY OF DIFFERENT ANTIHYPERTENSIVE DRUG CLASSES FOR CARDIOVASCULAR DISEASE PREVENTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Objective: No single trial has compared all major antihypertensive drug classes head-to-head and current guidelines give different recommendations for first-line agents. Our aim was to assess the efficacy for cardiovascular disease prevention as well as acceptability across all antihypertensive drug classes. Design and method: We performed a systematic review and network meta-analysis guided by the recommendations from the Cochrane collaboration. We included all trials assessing any antihypertensive agent against another agent or placebo with at least 1000 patient-years of follow-up in each treatment arm. Risk of bias was assessed using Cochrane Collaborations RoB2 tool, and trials at high risk of bias were excluded from the analysis. Odds ratios from individual trials were pooled using random-effects network meta-analysis, with composite major cardiovascular events as the primary outcome for efficacy, and treatment discontinuation as the primary outcome from acceptability. Results: 85 trials, including 406 067 participants followed for an average of 4.0 years, were included in the analysis. Mean age was 64.0 years and 41% percent were women. Overall, 15 different drug classes, drug class combinations and placebo were included in the network. There were some signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), and calcium channel blockers (CCB) all reduced the risk of major cardiovascular events compared to placebo. Diuretics showed a similar trend, whereas beta-blockers (BB) and renin inhibitors did not. For acceptability, ARB and CCB were comparable to placebo, diuretics showed a non-significant trend towards more discontinuations, whereas ACEi, BB and alpha-blockers were significant more prone to treatment discontinuation compared to placebo and other agents. Conclusions: This is the most comprehensive network meta-analysis of antihypertensive agents to date. Our findings indicate that ACEi, ARB and CCB are the most effective agents in preventing major cardiovascular events. Based on a more beneficial acceptability profile, ARB and CCB may be considered most appropriate as first-line agents, although these findings should be interpreted with caution due inconsistency.

Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study

BackgroundCoronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. MethodsAdult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Outcomes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. ConclusionsThe CORONA-VTE-Network study will share contemporary information related to rates of cardiovascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

PS-BPC06-10: FATTY LIVER INDEX AND CARDIOVASCULAR RISK IN HYPERTENSIVE PATIENTS

Objective: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing rapidly worldwide affecting 25–30% of population. Fatty liver index (FLI) is a validated marker of NAFLD and can be used as a screening tool for hepatic steatosis. The purpose of the study was to evaluate the relationship between FLI and the risk of major cardiovascular events in hypertensive patients. Design and method: 903 hypertensive patients without history of cardiovascular disease participated in the study (mean age 52.7 ± 11.4 years; males 55%; baseline clinic BP 149.8 ± 15.2/95.5 ± 10.1 mmHg). Participants were prospectively evaluated for a mean follow-up period of 6.0 ± 3.3 years with at least one annual visit. The diagnosis of NAFLD was based on FLI and consequently patients were divided in two groups according to the presence of NAFLD. The primary endpoint was a composite of major cardiovascular events. Results: The incidence of cardiovascular events during the follow up was 8.5% (n = 77). Patients without NAFLD (n = 625) had better BP control compared to their counterparts with NAFLD (n = 278) during follow up (43% vs 33%, p = 0.02). A Cox-regression analysis indicated that age (hR 1.09 CI 1.04–1.13, p &lt; 0.01), smoking (hR 2.4 CI 1.1–5.2, p = 0.03) and FLI (hR 2.7 CI 1.9–4.1, p &lt; 0.001) were significant independent determinants of the outcome. The presence of NAFLD at baseline visit was also a significant independent determinant of the outcome (hR 5.2 CI 2.4–11.1, p &lt; 0.001). Conclusions: In conclusion, FLI has an independent prognostic value for the incidence of cardiovascular events in hypertensive patients. Therefore, it could be useful in identifying patients at higher risk of cardiovascular events. Further studies will clarify whether the early treatment of NAFLD could reduce the incidence of cardiovascular disease.

Inclisiran and cardiovascular events: a patient-level analysis of phase III trials.

Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established. Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)]. This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.

Rationale and Design of LAPIS: A Multicenter Prospective Cohort Study to Investigate the Efficacy and Safety of Low-Dose Aspirin in Elderly Chinese Patients.

Although aspirin can effectively reduce the occurrence of atherothrombosis, it is significantly associated with increased bleeding, with elderly individuals being at increased risk of cardiovascular diseases(CVDs) and hemorrhage. While the adverse effects of aspirin can be reduced by using the lowest effective dose, its optimal dose remains undetermined in the elderly Chinese population with both higher cardiovascular and bleeding risks. This study aims to assess the current status of aspirin therapy in real-world clinical settings as well as investigate the efficacy and safety of different doses of aspirin intake (≤ 50 mg/d and > 50 mg/d) for CVD prevention and management in elderly Chinese individuals. The Low-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly Study (LAPIS) is a multicenter, prospective, observational cohort study. At least 10,000 people aged ≥ 60 years who require long-term aspirin therapy will be recruited. The effectiveness outcome is a composite of major cardiovascular events(MACEs), including nonfatal myocardial infarction, unstable angina, arteriosclerotic disease requiring surgery or intervention, nonfatal stroke, transient ischemic attack, or cardiovascular death (excluding intracranial hemorrhage). The safety outcome is a composite of the first occurrence of fatal bleeding, major bleeding and minor bleeding. Information on the incidence of aspirin-associated gastrointestinal adverse events will also be collected for safety analyses. Outcome measurements will be performed at intervals of 30 days, 3 months, 6 months and then every 6 months for the next 3 years. The results of the LAPIS study will ascertain the efficacy and safety of different doses of aspirin for the prevention and management of CVD, thereby providing evidence to determine the optimal evidence-based dose of aspirin therapy in Chinese elderly individuals. ChiCTR1900021980 (chictr.org.cn). Registered on March 19, 2019.

Relationships between endogenous and exogenous testosterone and cardiovascular disease in men.

In this narrative review, we discuss the evidence about the controversy about the cardiovascular effects of endogenous and exogenous testosterone in men. Prospective cohort studies with follow-up of ~5-15years generally indicate no association or a possible inverse relationship between serum endogenous testosterone concentrations and composite major cardiovascular events, cardiovascular deaths and overall mortality. Pharmacoepidemiological studies of large databases generally show no association between testosterone therapy and incident major cardiovascular events, and some pharmacoepidemiological studies demonstrate an association with decreased overall mortality. Randomized, placebo-controlled trials indicate that there is no increased incidence of overall major cardiovascular events with 1-3years of testosterone therapy. These placebo-controlled trials have major limitations including small numbers of participants, short duration of testosterone therapy and follow-up, and lack of systematic adjudication of cardiovascular events. Overall, the evidence indicates that endogenous testosterone concentrations and testosterone therapy at physiological dosages confer no or minimal effects on the incidence of cardiovascular outcomes. There is insufficient evidence to make conclusions about testosterone therapy for patients at high risk of cardiovascular events (e.g., men with recent myocardial infarctions or stroke and men with recurrent idiopathic deep venous thromboses). In general, clinicians should avoid prescribing supraphysiological testosterone therapy to hypogonadal men or men with slightly low to low-normal serum testosterone concentrations and no identified disorder of the hypothalamus-pituitary-testicular axis because of the uncertain cardiovascular risks and the lack of proven health benefits. For most men with bona fide hypogonadism, benefits of testosterone therapy exceed the potential risk of adverse cardiovascular effects.

Lipoprotein (a) and new-onset type-2 diabetes in patients with familial combined hyperlipidemia: a 9 years follow-up study

Abstract Background Elevated lipoprotein(a) [Lp(a)] levels have been related with increased cardiovascular (CV) risk in the general population. However, its relationship with type-2 diabetes and CV risk in patients with Familial Combined Hyperlipidemia (FCH) is rather unclear. Thus, the aim of our study was to investigate the prognostic role of Lp(a) regarding new-onset type-2 diabetes and major adverse cardiovascular outcomes in patients with FCH. Methods 485 patients from the outpatient lipid clinic of our hospital (301 males,mean age 49.8±10.8 years, 35%smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FCH criteria participated in the study. Participants were evaluated for a mean follow-up period of 8.9±7.5 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile, and levels of Lp(a). All subjects were on lipid-lowering medication (statin and ezetimibe or fibrate) during the follow-up period. The endpoints of our study was new-onset diabetes and the composite of major CV events (coronary artery disease events and stroke). Results The incidence of new-onset diabetes during the follow-up period was 10% (n=42). The group of patients with new-onset diabetes (n=42) had lower levels of Lp(a) at baseline compared to those without new-onset diabetes (n=376) (23.8±19.2 vs 32.9±39.5 mg/dl, p=0.01). Also, those with new-onset diabetes had a lower percentage of increased Lp(a) levels (≥30 mg/dl) at baseline compared to those without new-onset diabetes (21% vs 34%). Multiple Cox regression analysis revealed that increased Lp(a) (≥30 mg/dl) is an independent predictor of lower diabetes incidence during the follow-up period (HR 0.39, 95% CI 0.17–0.90), after adjustment for confounding factors. Moreover, the incidence of new-onset CV events in the total population was 6.4% (n=31).In the group of patients with increased Lp(a) levels at baseline (≥30 mg/dl, n=159, 33%) there was a trend towards a greater incidence of CV events during the follow-up period, compared to the group of patients with lower Lp(a) levels (&amp;lt;30 mg/dl, n=326, 67%), although the difference between the two groups was not statistically significant (8.8% vs 5.1%, p=0.1). Conclusions In patients with FCH, increased baseline Lp(a) is an independent predictor of lower incidence of new-onset type-2 diabetes after an almost 9 years follow-up period. Moreover, increased Lp(a) seems to convey an increased CV risk also in patients with FCH. Funding Acknowledgement Type of funding sources: None.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study

There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. Funding sources are listed at the end of the Article.

THE PROGNOSTIC VALUE OF FATTY LIVER INDEX FOR CARDIOVASCULAR EVENTS IN HYPERTENSIVE PATIENTS

Objective: The prevalence of on-alcoholic fatty liver disease (NAFLD) has been increasing rapidly worldwide affecting 25–30% of population. Fatty liver index (FLI) is a validated marker of NAFLD and can be used as a screening tool for hepatic steatosis. The purpose of the study was to evaluate the relationship between FLI and the risk of major cardiovascular events in hypertensive patients. Design and method: 903 hypertensive patients without history of cardiovascular disease participated in the study (mean age 52.7 ± 11.4 years; males 55%; baseline clinic BP 149.8 ± 15.2/95.5 ± 10.1 mmHg). Participants were prospectively evaluated for a mean follow-up period of 6.0 ± 3.3 years with at least one annual visit. The diagnosis of NAFLD was based on FLI and consequently patients were divided in two groups according to the presence of NAFLD. The primary endpoint was a composite of major cardiovascular events. Results: The incidence of cardiovascular events during the follow up was 8.5% (n = 77). Patients without NAFLD (n = 625) had better BP control compared to their counterparts with NAFLD (n = 278) during follow up (43% vs 33%, p = 0.02). A Cox-regression analysis indicated that age (HR 1.09 CI 1.04–1.13, p &lt; 0.01), smoking (HR 2.4 CI 1.1–5.2, p = 0.03) and FLI (HR 2.7 CI 1.9–4.1, p &lt; 0.001) were significant independent determinants of the outcome. The presence of NAFLD at baseline visit was also a significant independent determinant of the outcome (HR 5.2 CI 2.4–11.1, p &lt; 0.001). Conclusions: FLI has an independent prognostic value for the incidence of cardiovascular events in hypertensive patients. Therefore, it could be useful in identifying patients at higher risk of cardiovascular events. Further studies will clarify whether the early treatment of NAFLD could reduce the incidence of cardiovascular disease.