Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease最新文献

{"title":"Risk Burden of Coronary Perforation in Chronic Total Occlusion Recanalization: Latin American CTO Registry Analysis","authors":"M. Ribeiro, Carlos M Campos, Lucio T. Padilla, A. C. B. da Silva, J. E. T. de Paula, Marco A. Alcántara, Ricardo Santiago, Franklin Hanna, Franciele R da Silva, Karlyse C Belli, L. Azzalini, P. P. de Oliveira, G. Araujo, V. Sucato, K. Mashayekhi, A. Galassi, A. Abizaid, A. Quadros","doi":"10.1161/JAHA.121.024815","DOIUrl":"https://doi.org/10.1161/JAHA.121.024815","url":null,"abstract":"Background Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention‐Chronic total occlusions scores were 2.0 (1.0–3.0) and 1.0 (0.0–2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1‐year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%; P<0.01). Using weighted composite end point, perforation was associated with increased bleeding and ischemic events at 6 months (P=0.04) and 1 year (P<0.01). We found as independent predictors associated with coronary perforation during CTO PCI: maximum activated clotting time (P<0.01), Multicenter CTO Registry in Japan score ≥2 (P=0.05), antegrade knuckle wire (P=0.04), and right coronary artery CTO PCI (P=0.05). Conclusions Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow‐up.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73884229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the WATCH‐DM and TRS‐HFDM Risk Scores to Predict the Risk of Incident Hospitalization for Heart Failure Among Adults With Type 2 Diabetes: A Multicohort Analysis","authors":"M. Segar, Kershaw V. Patel, A. Hellkamp, M. Vaduganathan, Y. Lokhnygina, Jennifer B. Green, S. Wan, A. Kolkailah, R. Holman, E. Peterson, V. Kannan, D. Willett, D. McGuire, A. Pandey","doi":"10.1161/JAHA.121.024094","DOIUrl":"https://doi.org/10.1161/JAHA.121.024094","url":null,"abstract":"Background The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HFDM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P<0.001 for both). In the electronic health record cohort, the integer‐based WATCH‐DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood‐Nam‐D’Agostino P=0.96). TRS‐HFDM score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice. Conclusions The WATCH‐DM and TRS‐HFDM risk scores can discriminate risk of HF among intermediate‐risk populations with type 2 diabetes.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74530878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil‐to‐Lymphocyte Ratios in Patients Undergoing Aortic Valve Replacement: The PARTNER Trials and Registries","authors":"B. Shahim, B. Redfors, B. Lindman, Shmuel Chen, T. Dahlén, Tamim Nazif, S. Kapadia, Z. Gertz, Aaron Crowley, Ditian Li, V. Thourani, S. Kodali, A. Zajarías, V. Babaliaros, R. Guyton, S. Elmariah, H. Herrmann, D. Cohen, M. Mack, Craig R. Smith, M. Leon, I. George","doi":"10.1161/JAHA.121.024091","DOIUrl":"https://doi.org/10.1161/JAHA.121.024091","url":null,"abstract":"Background The neutrophil‐to‐lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow‐up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5–24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70–4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18–1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1‐unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82–0.89; P<0.0001). Conclusions Elevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91212986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intervention Adherence in REHAB‐HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events","authors":"M. Nelson, Olivia N. Gilbert, P. Duncan, D. Kitzman, G. Reeves, D. Whellan, R. Mentz, Haiying Chen, L. Hewston, Karen M Taylor, A. Pastva","doi":"10.1161/JAHA.121.024246","DOIUrl":"https://doi.org/10.1161/JAHA.121.024246","url":null,"abstract":"Background The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial showed that a novel, early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality of life in older, frail patients hospitalized for acute decompensated heart failure. This analysis examined the relationship between intervention adherence and outcomes. Methods and Results Adherence was defined as percent of sessions attended and percent of sessions attended adjusted for missed sessions for medical reasons. Baseline characteristics were examined to identify predictors of session attendance. Associations of session attendance with change in physical function (Short Physical Performance Battery [primary outcome], 6‐minute walk distance, quality of life [Kansas City Cardiomyopathy Questionnaire], depression, and clinical events [landmarked postintervention]) were examined in multivariate analyses. Adherence was 67%±34%, and adherence adjusted for missed sessions for medical reasons was 78%±34%. Independent predictors of higher session attendance were the following: nonsmoking, absence of myocardial infarction history and depression, and higher baseline Short Physical Performance Battery. After adjustment for predictors, adherence was significantly associated with larger increases in Short Physical Performance Battery (parameter estimate: β=0.06[0.03–0.10], P=0.001), 6‐minute walk distance (β=1.8[0.2–3.5], P=0.032), and Kansas City Cardiomyopathy Questionnaire score (β=0.62[0.26–0.98], P=0.001), and reduction in depression (β=−0.08[−0.12 to 0.04], P<0.001). Additionally, higher adherence was significantly associated with reduced 6‐month all‐cause rehospitalization (rate ratio: 0.97 [0.95–0.99], P=0.020), combined all‐cause rehospitalization and death (0.97 [0.95–0.99], P=0.017), and all‐cause rehospitalization days (0.96 [0.94–0.99], P=0.004) postintervention. Conclusions In older, frail patients with acute decompensated heart failure, higher adherence was significantly associated with improved patient‐centered and clinical event outcomes. These data support the efficacy of the comprehensive adherence plan and the subsequent intervention‐related benefits observed in REHAB‐HF. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02196038.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76077024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53‐Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction","authors":"Xiaonan Chen, Hao Lin, Weiyao Xiong, Jia-Yu Pan, Shuying Huang, Shan Xu, Shufang He, Ming Lei, A. C. Chang, Huili Zhang","doi":"10.1161/JAHA.121.024582","DOIUrl":"https://doi.org/10.1161/JAHA.121.024582","url":null,"abstract":"Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high‐fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second‐generation and third‐generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second‐generation telomerase RNA component knockout (at 6 weeks) and third‐generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial‐specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride challenged murine model.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75233013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes","authors":"T. Gallo, C. Heise, R. Woosley, J. Tisdale, Malinda S. Tan, S. Gephart, Corneliu C Antonescu, D. Malone","doi":"10.1161/JAHA.122.024338","DOIUrl":"https://doi.org/10.1161/JAHA.122.024338","url":null,"abstract":"Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high‐risk medications in patients at risk of TdP, but alerts are often ignored. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class (P<0.05 for all actions). Conclusions A modified Tisdale QT risk score–based CDS that offered relevant single‐click management options yielded a high action/response rate. Actions taken by clinicians varied depending on the class of the medication that evoked the TdP risk advisory, but the most frequent was ordering an ECG.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76552627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans","authors":"Hao Zhang, K. Jamieson, J. Grenier, A. Nikhanj, Zeyu Tang, Faqi Wang, Shaohua Wang, J. Seidman, C. Seidman, R. Thompson, J. Seubert, G. Oudit","doi":"10.1161/JAHA.121.022853","DOIUrl":"https://doi.org/10.1161/JAHA.121.022853","url":null,"abstract":"Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non‐invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non‐failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1–150.3] versus 137.4 [109.2–165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF‐MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF‐MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron‐deficient hearts. Mechanistically, iron uptake pathways were impeded in HF‐MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non‐invasively monitor MID.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91029731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Pressure–Lowering Effects of Omega‐3 Polyunsaturated Fatty Acids: Are These the Missing Link to Explain the Relationship Between Omega‐3 Polyunsaturated Fatty Acids and Cardiovascular Disease?","authors":"M. George, Ajay K. Gupta","doi":"10.1161/JAHA.121.026258","DOIUrl":"https://doi.org/10.1161/JAHA.121.026258","url":null,"abstract":"In this issue of the Journal of the American Heart Association (JAHA), Zhang and colleagues1 have reported that the intake of omega3 (ω3) polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) are associated with a reduction in blood pressure (BP) and identified the optimal dose of 2 to 3 g/d. Although these findings are not entirely novel, they are robust and provide insights into the longstanding debate on the role of ω3 PUFAs in modifying cardiovascular risk.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91132709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Health Care Providers' Experiences of Providing Collaborative Palliative Care for Patients With Advanced Heart Failure At Home: A Qualitative Study","authors":"C. Graham, R. Schonnop, T. Killackey, D. Kavalieratos, S. Bush, L. Steinberg, Susanna Mak, Kieran Quinn, S. Isenberg","doi":"10.1016/j.jpainsymman.2022.04.117","DOIUrl":"https://doi.org/10.1016/j.jpainsymman.2022.04.117","url":null,"abstract":"","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80669049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidome‐ and Genome‐Wide Study to Understand Sex Differences in Circulatory Lipids","authors":"R. Tabassum, S. Ruotsalainen, L. Ottensmann, M. Gerl, C. Klose, T. Tukiainen, M. Pirinen, K. Simons, E. Widén, S. Ripatti","doi":"10.1101/2022.05.30.22275704","DOIUrl":"https://doi.org/10.1101/2022.05.30.22275704","url":null,"abstract":"Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0x10-4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, and highlights need for sex- and age-specific prevention strategies.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85388967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}