Favorable Cardiovascular Risk Profile Research Articles

Does cardiorespiratory fitness moderate the relationship between overweight, cardiovascular risk markers and mental health among forcibly displaced individuals living in a Greek refugee camp?

Refugees may have an increased risk of developing overweight/obesity as they often experience a nutritional transition. Because maintaining good cardiorespiratory fitness can help reduce the negative impact of excess weight on overall health, the objective of this study was to examine whether fitness moderates the relationship between weight status and cardiovascular and mental health outcomes in forcibly displaced individuals living in a Greek refugee camp. A sample of 142 forcibly displaced individuals were recruited. Cardiorespiratory fitness was assessed with the submaximal Åstrand-Rhyming bicycle ergometer test. Blood pressure, blood lipids, blood glucose, and hs-CRP were assessed as physical health outcomes, whereas post-traumatic stress disorder, depression and anxiety symptoms, pain, and quality of life were assessed as mental health outcomes. Main and interaction effects were tested via analyses of covariance (ANCOVAs). Almost 50% of the participants were overweight/obese, more than 60% presented with very poor fitness levels, and the percentage of participants with very poor fitness levels was particularly high among overweight/obese participants. Whereas overweight/obesity was associated with a less favorable body composition and cardiovascular risk profile, poor fitness was associated with a higher percentage of body fat and a lower percentage of muscle mass. Cardiorespiratory fitness did not moderate the relationship between overweight/obesity and most of the assessed health outcomes. Only limited support was found for the applicability of the fit-but-fat concept to our population of forcibly displaced individuals. Public health services should prioritize measures to prevent overweight/obesity and associated diseases in refugee camps. Moreover, efforts are needed to improve the fitness of camp residents via exercise/sport interventions.

Myocardial mechano-energetic efficiency is not impaired in patients with metabolically healthy overweight and obesity.

Reduced myocardial mechano-energetic efficiency (MEE) was associated with BMI. Subgroups of individuals with increased BMI but favorable cardiovascular risk profile were identified as individuals with "metabolically healthy overweight" (MHOW) and "metabolically healthy obesity" (MHO), respectively. We aim to investigate whether those with MHOW/MHO, defined as those having none of the components of metabolic syndrome, exhibit impaired MEE compared with their unhealthy counterparts. Myocardial MEE per gram of left ventricular mass (MEEi) was assessed by echocardiography in 2190 nondiabetic individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study who were divided, according to BMI and metabolic status, into groups of individuals with metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHOW, metabolically unhealthy overweight (MUOW), MHO, and metabolically unhealthy obesity (MUO). After adjusting for age and sex, no differences in myocardial MEEi were observed among individuals with MHNW, MHOW, and MHO (p = 0.56). Myocardial MEEi was comparable among individuals with MUNW, MUOW, and MUO (p = 0.21). Individuals with MHNW, MHOW, and MHO displayed significantly higher myocardial MEEi compared with their unhealthy counterparts. Increased BMI is not an obligate determinant for reduced myocardial MEEi. Other known components of metabolic syndrome rather than increased BMI contributed to reduced myocardial MEEi.

Abstract WMP107: Exploration of the Inflammatory Profile of Gluteofemoral Adipose Tissue Distribution Supports Role of Targeting Inflammation to Further Decrease Cardiovascular Risk

Introduction: Recent evidence suggests that body fat distribution is associated with cardiovascular risk. We have previously shown that gluteofemoral adipose tissue (GFAT) distribution is associated with a favorable cardiovascular risk profile. Given the emerging role of inflammation in cardiovascular health, we explored the inflammatory profile of GFAT and the possible mediatory role of inflammatory cytokines underlying the association between GFAT and cardiovascular risk. Methods: As previously described, utilizing GWAS data and univariable Mendelian Randomization (MR) analyses we explored the association between genetically proxied GFAT (n= 37,750) and 6 vascular outcomes [ischemic stroke (IS) (n=62,100), large artery stroke (LAS) (n=6,399), small vessel stroke (SVS) (n=6,811), coronary artery disease (CAD) (n=181,522), lacunar stroke (n=6,030), and carotid intima media thickness (cIMT) (n=45,185)]. We also performed univariable MR between GFAT and 40 circulating inflammatory markers (n=75,000) and derived the significant profile after FDR correction. We then explored the mediatory effect of the inflammatory profile on the cardiovascular outcomes after performing two-step mediation MR. Cytokines that showed significant univariable MR associations with both GFAT and the vascular outcomes were considered candidate mediators. Results: Genetically proxied GFAT was associated with decreased risk of IS (p=0.006), LAS (p=0.016), SVS (p<0.001), CAD (p<0.001), and lacunar stroke (p=0.001), and lower mean cIMT (p=0.001). GFAT showed significant association with 9 inflammatory cytokines (Figure) . HGF was a candidate mediator underlying the GFAT-CAD association and IL-2 showed significant suppression effect in the GFAT-cIMT axis (β GFAT-cIMT =-0.07, p=0.001; β IL-2-cIMT =0.01, p=0.0126). Conclusion: In the context of a favorable body fat distribution, targeting IL-2 may further enhance the protective role of GFAT on cardiovascular risk.

Abstract 12107: Cardiovascular Outcomes Associated With Gonadotropin-Releasing Hormone Antagonists vs Gonadotropin-Releasing Hormone Agonists for Prostate Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

Background: Androgen deprivation therapy (ADT), comprising the administration of Gonadotropin-releasing hormone (GnRH) agonists and antagonists, is a widely utilized treatment for prostate cancer patients and has been universally accepted as the first-line treatment for symptomatic metastatic prostatic cancer. While ADT has proven effective, concerns about its impact on cardiovascular health have emerged. Conflicting results regarding the association between ADT and cardiovascular events have been reported in the most recent PRONOUNCE trial hence a meta-analysis to systematically evaluate the evidence is desired. Aim: The primary objective of this meta-analysis was to investigate and compare the effects of GnRH agonists and antagonists on cardiovascular events in patients with prostate cancer. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: 9 studies met the eligibility criteria and were included in the final analysis. A total of 3648 patients were randomized to receive either an agonist (n=1375) or an antagonist (n=2273). The pooled results revealed a significant reduction in the risk of adverse cardiovascular events by 48% with the use of GnRH agonists compared to GnRH antagonists (RR=0.52; 95% CI=0.39-0.71; p<0.01). Furthermore, GnRH agonists also decreased the risk of all-cause mortality by 46% (RR=0.54; 95% CI= 0.33-0.88; p=0.01) and cardiovascular mortality by 78% (RR= 0.22; 95% CI= 0.07-0.76; p=0.02) compared to GnRH antagonists. Conclusion: The findings of this meta-analysis reveal the favorable cardiovascular risk profile associated with GnRH agonists, supporting their role as a preferred treatment option over GnRH antagonists.

A comparison of cardiovascular and pulmonary morbidities and risk factors in breast cancer survivors compared to an age-matched female control group in the Lifelines prospective population cohort.

To provide more insight into late treatment-related toxicities among breast cancer (BC) survivors by comparing morbidities and risk factors between BC survivors and age-matched controls. All female participants diagnosed with BC before inclusion in Lifelines, a population-based cohort in the Netherlands, were selected and matched 1:4 to female controls without any oncological history on birth year. Baseline was defined as the age at BC diagnosis. Outcomes were obtained from questionnaires and functional analyses performed at entry to Lifelines (follow-up 1; FU1) and several years later (FU2). Cardiovascular and pulmonary events were defined as morbidities that were absent at baseline but present at FU1 or FU2. The study consisted of 1,325 BC survivors and 5,300 controls. The median period from baseline (i.e., BC treatment) to FU1 and FU2 was 7 and 10 years, respectively. Among BC survivors more events of heart failure (OR: 1.72 [1.10-2.68]) and less events of hypertension (OR: 0.79 [0.66-0.94]) were observed. At FU2, more electrocardiographic abnormalities were found among BC survivors compared to controls (4.1% vs. 2.7%, respectively; p=0.027) and Framingham scores for the 10-year risk of coronary heart disease were lower (difference: 0.37%; 95% CI [-0.70 to -0.03%]). At FU2, BC survivors had more frequently a forced vital capacity below the lower limit of normal than controls (5.4% vs. 2.9%, respectively; p=0.040). BC survivors are at risk of late treatment-related toxicities despite a more favourable cardiovascular risk profile compared to age-matched female controls.

Ideal Cardiovascular Health in Mexican Adults with CKD Living in Mexico City Versus Chicago.

Evidence suggests that Mexican adults living in Mexico have a more favorable cardiovascular risk profile than Mexican adults living in the U.S. However, this relationship has not been evaluated among patients with chronic kidney disease (CKD), which is a question of importance given the high risk for cardiovascular disease among patients with CKD. Using data from two ongoing observational cohort studies, we compared the prevalence of ideal cardiovascular health metrics (assessed by the American Heart Association "Life's Simple 7" criteria) in 309 Mexican adults with CKD living in Mexico City to 343 Mexican adults with CKD living in Chicago. Mexican adults with CKD living in Mexico City had a significantly higher prevalence of ideal body mass index (25 vs. 10%), diet (17 vs. 8%), total cholesterol (80 vs. 63%), blood pressure (43 vs. 25%), and fasting glucose (54 vs. 42%). Mexican adults with CKD living in both Mexico City and Chicago had low levels of cardiovascular health scores. Future work is needed to better understand the lower prevalence of ideal cardiovascular health metrics in Chicago as compared to Mexico City.

Clinical Characteristics and Outcomes Among People Living With HIV Undergoing Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Background Clinical characteristics and outcomes in people living with HIV (PLWH) undergoing percutaneous coronary intervention (PCI) remain poorly described. We sought to compare real-world treatment of coronary artery disease, as well as patient and procedural factors and outcomes after PCI between PLWH and uninfected controls. Methods and Results We utilized procedural registry data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program between January 1, 2009 and December 31, 2019 to analyze patients with obstructive coronary artery disease on angiography. In the PCI subgroup, we used inverse probability of treatment weighting and applied Cox proportional hazards to evaluate the association of HIV serostatus with outcomes, including all-cause mortality at 5 years. Among 184 310 patients with obstructive coronary artery disease, treatment strategy was similar between PLWH and controls-35.7% versus 34.2% PCI, 13.6% versus 15% coronary artery bypass grafting, and 50.7% versus 50.8% medical therapy. The PCI cohort consisted of 546 (0.9%) PLWH and 56 811 (99.1%) controls. PLWH undergoing PCI had well-controlled HIV disease, and compared with controls, were younger, more likely to be Black, had fewer traditional risk factors, more acute coronary syndrome, less extensive coronary artery disease, and similar types of stents and P2Y12 therapy. However, PLWH experienced worse survival as early as 6 months post-PCI, which persisted over time and amounted to a 21% increased mortality risk by 5 years (hazard ratio, 1.21 [95% CI, 1.03-1.42; P=0.02]). Conclusions Despite well-controlled HIV disease, a more favorable overall cardiovascular risk profile, and similar PCI procedural metrics, PLWH still have significantly worse long-term survival following PCI than controls.

Physical activity and risk of all-cause mortality in patients with stable angina pectoris: Effect modification by β-blocker treatment

BackgroundPhysical activity (PA) influences sympathetic stimulation, platelet activation as well as vascular function, and has been associated with improved health outcomes in patients with coronary heart disease. β-blocker therapy reduces sympathetic activity and improves platelet and endothelial function. We investigated if β-blocker treatment modifies the association of self-reported PA with the risk of all-cause mortality. MethodsA total of 2284 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) were studied. Using Cox modeling, we examined associations between PA (categorized as ‘sedentary/inactive’, ‘low’, ‘moderate’, and ‘high’) and all-cause mortality according to β-blocker therapy. ResultsDuring a median follow-up of 10.3 years, 390 patients (17.1%) died. Higher PA was generally associated with a more favorable cardiovascular risk profile. Compared to the patients who were sedentary or inactive, the age and sex adjusted HRs (95% CI) for all-cause mortality were 0.89 (0.66–1.20), 0.73 (0.57–0.95) and 0.72 (0.55–0.95) in the low, moderate and high PA group, respectively. However, and notably, these risk estimates were 0.85 (0.60–1.20), 0.65 (0.47–0.89) and 0.58 (0.41–0.81) in β-blocker treated subjects vs. 1.00 (0.57–1.78), 0.96 (0.61–1.52) and 1.20 (0.74–1.95) in non-treated groups (Pinteraction = 0.018). The results were essentially similar in the multivariable adjusted models. ConclusionsIn patients with suspected SAP, increased PA was associated with reduced mortality risk primarily in patients treated with β-blockers.

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.

NAFLD-related gene polymorphisms and all-cause and cause-specific mortality in an Asian population: the Shanghai Changfeng Study.

The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. To investigate the effects of the NAFLD risk alleles on the all-cause and cause-specific mortality in 5581 Chinese adults. The genome-wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. Genome-wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P=8.6×10-7 ). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29425.1 person-years of follow-up, the overall mortality was 816 per 100000 person-years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver-specific mortality (P for trend=0.034) but reduced cardiovascular mortality (P for trend=0.047). A composite genetic-predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver-specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver-specific mortality were found (Pinteraction <0.05). The reduced serum VLDL1 concentration was responsible for the increased liver-specific mortality related to NAFLD risk alleles. The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver-specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.

Regular Exercise is Associated with a More Favorable Cardiovascular Risk Profile, Better Quality of Life, Less Depression and Less Psychological Stress.

IntroductionIt is well documented that insufficient physical activity (PA) contributes substantially to cardiovascular diseases. The number of physically active people in Germany is still too low.MethodsIn ELITE study in Germany, 4602 participants are regularly examined for cardiovascular risk factors (CVRF). The aim is to motivate participants to improve their CVRF through individual recommendations and regular follow-up. Here, the PA data are presented in correlation with CVRF at baseline. A feature of this presentation is that the usual CVRF but also the effects on psychosocial factors were recorded simultaneously.ResultsParticipants were divided into 3 groups based on their PA: 1. frequent exercise (FE): daily to 2–3x per week (41.4%), 2. moderate exercise (ME): 1x/week to 2x/month (28.8%), 3. rarely exercise (RE): 1x/month to not at all (29.8%). Age did not differ in the 3 groups. The most common CVRF was arterial hypertension, which decreased significantly with an increase in PA. Diabetes, nicotine, and increased BMI were also significantly less frequent in group 1. Antihypertensives were taken less frequently in this group 1. Less physically active participants were significantly more likely to have 3 or more additional CVRF. While group 1 consumed more fruit (64%) and considerably less pork, in group 2 and 3 only 58.3% and 50.3% respectively included fruit in their diet. FE also had a favorable effect on stress, depression and general well-being, all of which were significantly better in group 1.ConclusionResults confirm the beneficial influences of exercise on known CVRF and on psychosocial parameters. The prevalence of several CVRF per person at low levels of sport is of particular concern, as these participants would benefit most. During a 5-year follow-up, participants will receive intensive education on the need to increase PA. It remains to be seen how successful the effort will be.

Abstract 13366: Cardiovascular Risk Profile of Middle Eastern Immigrants Living in the United States

Introduction: Middle Eastern (ME) immigrants are one of the fastest-growing groups in the US. Several studies have noted a relatively high burden of CVD in ME countries. In the US, while their risk profile has been partially described as part of immigrant studies, the burden of risk factors and ASCVD have not been studied in detail among ME immigrants. Methods: We used 2012-2018 data from the National Health Interview Survey (NHIS), a US nationally representative survey. ME origin was ascertained through self-reported region of birth. ASCVD and CVD risk factors were also self-reported. We compared these to US-born non-Hispanic white (NHW) individuals in the US, using chi-square tests and logistic regression models. Results: Among 139,778 adults included, 886 (representing 1.3 million individuals, mean age 46.8) were of ME origin, and 138,892 were US-born NHWs (representing 150 million US adults, mean age 49.3). ME participants were more likely to have higher education, lower income and be uninsured. The age-adjusted prevalence of hypertension (22.7% vs 27.8%) and obesity (22.1% vs 32%) were significantly lower in MEs vs NHWs participants, respectively. There were no significant differences between the groups in the age-adjusted prevalence of ASCVD, diabetes, hyperlipidemia, and smoking. Only physical inactivity was higher among ME individuals (Fig) . In multivariable analyses, ME participants had lower odds of hypertension (OR 0.71, 95% CI 0.61, 0.83) and obesity (OR 0.61, 95% CI 0.52, 0.72), and higher odds of physical inactivity (OR 1.30, 95% CI 1.11, 1.53), with no significant differences in the other factors or ASCVD (Fig) . Conclusions: ME immigrants in the US exhibit a more favourable cardiovascular risk profile compared to NHWs. Further studies are needed to determine whether this finding is related to lower risk, selection of a healthier ME subgroup in NHIS, or possible under-detection of cardiovascular risk factors in ME immigrants living in the US.

Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes.

BACKGROUNDWhether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown.METHODS AND RESULTSThis study included 4018 patients with acute coronary syndrome recruited in the ISAR‐REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all‐cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P=0.267). All‐cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P=0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89–2.28]; HRC: HR, 1.33 [95% CI, 1.04−1.72]; P for interaction=0.800).CONCLUSIONSPatients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1‐year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Impact of gender on long-term prognosis after transcatheter edge-to-edge repair for mitral regurgitation

Abstract Background A symptomatic and prognostic benefit by Transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) has been proven. A variety of individual factors including female sex has been suggested to be associated with adverse outcome in cardio-surgical procedures. Purpose While gender is factored in common risk factor models for adverse outcome, evidence on sex-specific differences in long-term outcome after TEER for MR is limited. We aimed to investigate the impact of gender on prognosis in a large monocentric cohort with long-term follow-up. Methods We analyzed survival stratified for gender after successful isolated edge-to-edge repair of MR in the period between 06/2010 and 03/2018 (exclusion of combined forms of TMVR) in a monocentric retrospective cohort by performing survival analyses and cox regression analyses. Results Consecutively, 627 patients (47.0% females, 57.4% functional MR; survival status was available in 96.7%) entered the study and were followed for a median follow-up period of 462 days [IQR 142–945 days]. Survival rates were 97.6% at discharge, 75.7% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7 years. Risk score as calculated by the Logistic Euroscore I did not differ significantly between females and males (at baseline: 25.0 [IQR 18.0/34.8] vs. 27.0 [18.4/40.1]%, p=0.093) and no relevant differences were found for in-hospital (2.0 vs. 2.7%, p=0.613), 30 days (4.8 vs. 6.5%, p=0.473) and 1-year mortality (27.0 vs. 25.3%, p=0.675). At the time of procedure, women were older (79.9 [IQR 75.6/84.4] vs. 78.3 [72.9/83.4] years, p&amp;lt;0.001), were less often affected by coronary artery disease (53.1% vs. 75.0% p&amp;lt;0.001), diabetes mellitus (23.7% vs. 31.3%, p=0.040) and impaired left ventricular function (44.5±12.9% vs. 38.9±13.4%, p&amp;lt;0.001). Regarding long-term survival, women had a better prognosis after MR-therapy, especially in functional etiology: e.g., 4-year survival in FMR 65.7 vs. 35.7%, p=0.006 (Figure 1). Remarkably, female sex was associated with a lower risk for long-term mortality in the Cox-regression models, especially in the FMR subgroup (total cohort: univariate HR 0.81 [0.62–1.04], p=0.101; FMR: univariate HR 0.68 [0.49–0.96], p=0.028). Conclusion In our cohort of patients undergoing TEER for MR, we found no evidence for an impaired short- and mid-term prognosis for female patients. In contrary and not as indicated by Logistic Euroscore, female sex was associated with better long-term survival in comparison to men despite higher median age, which might be partly explained by a slightly more favorable cardiovascular risk profile. Funding Acknowledgement Type of funding sources: None. Figure 1

P665 Cardiovascular risk profile in chronic auto-inflammatory diseases: a cross-sectional single center study

Abstract Background Chronic auto-inflammatory diseases are associated with an increased risk of arterial and venous cardiovascular diseases (CVD). Pathogenesis may be related to chronic inflammation and/or traditional CVD risk factors. We aimed to assess the prevalence of CVD and cardiovascular risk profile in inflammatory bowel disease (IBD), psoriasis (PSO) and spondylarthropathies (SpA). Methods This is a single center cross-sectional study at the depts. of Gastroenterology, Dermatology and Rheumatology. Patients ≥18 years underwent body measurements (blood pressure (BP), BMI, waist and hip circumference), laboratory analysis (plasma glucose, lipid spectrum) and completed a cardiovascular questionnaire (e.g. history of CVD, medication use). Multivariate linear and logistic regression models corrected for age and sex were applied to identify differences between groups.. Sensitivity analyses were performed excluding patients taking statins or anti hypertensive drugs. Within groups, association between lipid levels and clinical disease activity was assessed by stratification, and with CRP levels by Pearson correlation test. Results A total of 668 patients were included (335 males (50%), median age 47 years: 459 IBD (69%), 106 PSO (16%) and 103 SpA patients (15%). (Table 1) The prevalence of venous thromboembolisms was 6%, heart failure 3% and arterial CVD 8%. IBD patients had lower BMI, systolic BP, TC and LDL-c levels, and lower odds ratio of having diabetes, overweight and hypercholesterolemia, as compared to PSO and SpA, but a higher odds ratio of having VTE. (Table 2) These results were independent of statin of anti hypertensive drug use. All groups showed a trend towards higher levels of TC, HDL-c and LDL-c during disease remission as compared to active disease (Figure 1) Overall, TC and LDL-c levels were inversely correlated with CRP (R -.145, p=.002 and R -.111, p=.016); within groups a significant association was only observed in IBD. (Table 3, Figure 2) Conclusion IBD patients have a more favorable cardiovascular risk profile, as compared to PSO and SpA. Screening and early intervention for CVD risk factors requires different strategies for each population.

Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes.

Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). Pubertal youth (n = 284) aged 12-21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO2peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. In adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO2peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. Obesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.

Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry.

AimsDilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe.Methods and resultsPatients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01).ConclusionsWe observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence.

NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes

The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death.

Importance of Sensitive Vascular Measurements for Evaluating Effects of Lifestyle in Premenopausal Women.

Premenopausal women generally have a favorable cardiovascular risk profile, owing to young age and the protective effects of estrogen. Rates of hypertension and more advanced cardiovascular disease (CVD) are low in premenopausal women. A large body of epidemiological evidence has shown that lifestyle behaviors in midlife, i.e., cardiorespiratory fitness, physical activity, and healthy diet, are associated with lower risk of overt CVD and adverse cardiovascular outcomes in the future for men and women. Despite differences in future cardiovascular risk, brachial blood pressures might be similar between premenopausal women with favorable vs. unfavorable levels of lifestyle behaviors in early-to-mid-life. Here we make the case for deeper phenotyping by means of vascular function measurements, such as arterial stiffness, augmentation index, and endothelial function, to identify potential mechanistic pathways linking lifestyle behaviors in early-to-mid-adulthood with lifelong CVD risk in women. We describe considerations for vascular function measurement in premenopausal women and opportunities for investigators to fill in knowledge gaps to further our understanding of CVD risk assessment and CVD progression in premenopausal women.

Effects of leptin and adiponectin on the cardiovascular system

Elevated circulating leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of leptin depending on the pathophysiological context. Studies performed in mice deficient in leptin or in leptin receptors are often contradictory, showing both protective and deleterious effects of leptin. These effects appear to vary depending on the genetic background of the animal and the doses of leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile. Adiponectin exerts protective effects at all stages of development of atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of adipokines actions and show the complexity to use these biomarkers in cardiovascular diseases. Resistance to the action of these adipokines is one of the hypotheses put forward to explain these discrepancies.