Sex differences in the prognosis of patients with hypertrophic cardiomyopathy.
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ABSTRACT:
SUBMITTER: Kim M
PROVIDER: S-EPMC7921653 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Sex differences in the prognosis of patients with hypertrophic cardiomyopathy.
Kim Minkwan M Kim Bongsung B Choi You-Jung YJ Lee Hyun-Jung HJ Lee Heesun H Park Jun-Bean JB Lee Seung-Pyo SP Han Kyung-Do KD Kim Yong-Jin YJ Kim Hyung-Kwan HK
Scientific reports 20210301 1
We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' ...[more]
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Project description:BackgroundWe aimed to clarify the sex differences in various cardiovascular and non-cardiovascular outcomes, and to investigate whether sex differences in outcomes are affected by age in hypertrophic cardiomyopathy (HCM).MethodsA cohort of 835 patients with HCM initially evaluated during 2007-2019 were followed for a median of 6.4 years. Study outcomes were all-cause death, cardiovascular and non-cardiovascular death, sudden cardiac death (SCD)/SCD equivalent events, heart failure (HF) events, and the composite cardiovascular outcome including cardiovascular death, SCD/SCD equivalent events, admission for HF, and heart transplantation.ResultsWomen were 5 years older (women 59.9±13.5 vs. men 54.9±11.4 years), had worse dyspnea, and greater left ventricular (LV) diastolic dysfunction and obstructive physiology at presentation. Women compared to men had higher all-cause mortality and cardiovascular event rates, driven by more cardiovascular deaths and heart failure (HF) events. Conversely, non-cardiovascular mortality was not different between the sexes. Female sex was independently associated with all-cause death (HR 1.88, 95% CI 1.11-3.20) and composite cardiovascular events (HR 3.60, 95% CI 2.00-6.49), independent of age, body mass index, New York Heart Association class, SCD risk score, and LV ejection fraction. When stratified by the age of 60, sex differences were not significant at <60 years; however, at ≥60 years, women had worse LV diastolic function, greater obstructive physiology, as well as worse survival and composite cardiovascular outcomes. Sex differences in outcomes remained consistent after propensity score matching for age and other clinical characteristics.ConclusionsWomen with HCM have worse cardiovascular prognosis than men, driven by higher cardiovascular mortality and HF events. The negative impact of female sex on cardiac function and cardiovascular outcome became prominent at age ≥60 years, suggesting age-related sex differences in the prognosis of HCM.
| S-EPMC8880392 | biostudies-literature
Project description:BackgroundSex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM).Methods and resultsA total of 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 to 2011. Compared to male patients, at baseline female patients were older at diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), and had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year follow-up period (range 2-7 years), survival analysis showed that the incidences of mortality from all causes, cardiovascular death and progression to chronic heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21-3.95, P = 0.010; HR 2.19, 95% CI 1.17-4.09, P = 0.014; HR 1.73, 95% CI 1.12-2.69, P = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was identified only in patients younger than 50 years old (P = 0.011, 0.011 and 0.009, respectively), but not for those 50 years or older.ConclusionOur results suggest that female sex is associated with worse survival and heart failure in HCM patients. Further studies are required to determine whether female hormones modify the clinical expression and prognosis of HCM.
| S-EPMC4105411 | biostudies-literature
Project description:IntroductionApical hypertrophic cardiomyopathy (ApHCM) is a subtype of hypertrophic cardiomyopathy (HCM) that affects up to 25% of Asian patients and is not as well understood in non-Asian patients. Although ApHCM has been considered a more "benign" variant, it is associated with increased risk of atrial and ventricular arrhythmias, apical thrombi, stroke, and progressive heart failure. The occurrence of pulmonary hypertension (PH) in ApHCM, due to elevated pressures on the left side of the heart, has been documented. However, the exact prevalence of PH in ApHCM and sex differences remain uncertain.MethodsWe sought to evaluate the prevalence, risk associations, and sex differences in elevated pulmonary pressures in the largest cohort of patients with ApHCM at a single tertiary center. A total of 542 patients diagnosed with ApHCM were identified using ICD codes and clinical notes searches, confirmed by cross-referencing with cardiac MRI reports extracted through Natural Language Processing and through manual evaluation of patient charts and imaging records.ResultsIn 414 patients, echocardiogram measurements of pulmonary artery systolic pressure (PASP) were obtained at the time of diagnosis. The mean age was 59.4 ± 16.6 years, with 181 (44%) being females. The mean PASP was 38 ± 12 mmHg in females vs. 33 ± 9 mmHg in males (p < 0.0001). PH as defined by a PASP value of > 36 mmHg was present in 140/414 (34%) patients, with a predominance in females [79/181 (44%)] vs. males [61/233 (26%), p < 0.0001]. Female sex, atrial fibrillation, diagnosis of congestive heart failure, and elevated filling pressures on echocardiogram remained significantly associated with PH (PASP > 36 mmHg) in multivariable modeling. PH, when present, was independently associated with mortality [hazard ratio 1.63, 95% CI (1.05-2.53), p = 0.028] and symptoms [odds ratio 2.28 (1.40, 3.71), p < 0.001].ConclusionPH was present in 34% of patients with ApHCM at diagnosis, with female sex predominance. PH in ApHCM was associated with symptoms and increased mortality.
| S-EPMC10808763 | biostudies-literature
Project description:AimsTransthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period.Methods and resultsAnalysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056).ConclusionThis study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.
| S-EPMC10087683 | biostudies-literature
Project description:Background: Sex-differences in clinical presentation contribute to the phenotypic heterogeneity of hypertrophic cardiomyopathy (HCM) patients. While disease prevalence is higher in men, women present with more severe diastolic dysfunction and worse survival. Until today, little is known about the cellular differences underlying sex-differences in clinical presentation. Methods: To define sex-differences at the protein level, we performed a proteomic analysis in cardiac tissue obtained during myectomy surgery to relieve left ventricular outflow tract obstruction of age-matched female and male HCM patients harboring a sarcomere mutation (n = 13 in both groups). Furthermore, these samples were compared to 8 non-failing controls. Women presented with more severe diastolic dysfunction. Results: Out of 2099 quantified proteins, direct comparison of male, and female HCM samples revealed only 46 significantly differentially expressed proteins. Increased levels of tubulin and heat shock proteins were observed in female compared to male HCM patients. Western blot analyses confirmed higher levels of tubulin in female HCM samples. In addition, proteins involved in carbohydrate metabolism were significantly lower in female compared to male samples. Furthermore, we found lower levels of translational proteins specifically in male HCM samples. The disease-specificity of these changes were confirmed by a second analysis in which we compared female and male samples separately to non-failing control samples. Transcription factor analysis showed that sex hormone-dependent transcription factors may contribute to differential protein expression, but do not explain the majority of protein changes observed between male and female HCM samples. Conclusion: In conclusion, based on our proteomics analyses we propose that increased levels of tubulin partly underlie more severe diastolic dysfunction in women compared to men. Since heat shock proteins have cardioprotective effects, elevated levels of heat shock proteins in females may contribute to later disease onset in woman, while reduced protein turnover in men may lead to the accumulation of damaged proteins which in turn affects proper cellular function.
| S-EPMC7956946 | biostudies-literature
Project description:Background: Female sex is reported to be associated with poor prognosis in hypertrophic cardiomyopathy (HCM). The plasma B-type natriuretic peptide (BNP) concentration is a prognostic predictor in HCM. However, the effect of sex on BNP concentrations remains unclear among HCM patients. Methods and Results: Patient records in the Clinical Personal Records of HCM national database of the Japanese Ministry of Health, Labour and Welfare from 2009 to 2014 were analyzed. Of 3,570 HCM patients, 611 in whom BNP concentrations were assessed at both baseline and the 2-year follow-up were included in this analysis. The mean age was 60.4 years and 254 (41.6%) patients were female. Median (interquartile range) BNP concentrations were higher in females than males at both baseline (320.3 [159.0-583.1] vs. 182.8 [86.1-363.9] pg/mL; P<0.001) and the 2-year follow-up (299.2 [147.0-535.3] vs. 161.0 [76.2-310.0] pg/mL; P<0.001). Female sex was associated with higher natural log-transformed BNP at the 2-year follow-up regardless of clinical characteristics, including echocardiographic findings and BNP concentrations at baseline (coefficient 0.31; 95% confidence interval 0.13-0.48; P<0.001). Cubic spline analysis showed that, among patients with high BNP concentrations at baseline, females had higher BNP concentrations at the 2-year follow-up than males. Conclusions: In HCM, female sex was associated with higher BNP concentrations than male sex, independent of clinical characteristics, including BNP concentrations at baseline.
| S-EPMC8492405 | biostudies-literature
Project description:BackgroundThis study aimed to explore the effect of sex on left atrial (LA) remodeling and its relationship with myocardial fibrosis in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods and resultsA total of 85 patients with HOCM were enrolled. Myocardial fibrosis was quantified by the collagen volume fraction (CVF) in myocardial samples. The early atrial peak of emptying rate (PER-E) was assessed by LA volume/time (V/t) curves derived from cardiac magnetic resonance (CMR) imaging analysis. The PER-E index was PER-E normalized by left ventricular (LV) filling volume. Patients with HOCM showed a lower PER-E index than healthy controls (P = 0.027). Compared with men, the PER-E (P < 0.001) and the PER-E indexes (P = 0.012) in women were lower. In CVF-stratified subgroups, a sex difference in the PER-E index was eliminated (P > 0.05). The CVF was correlated with the PER-E and PER-E indexes in both sexes (all P-values were <0.05). In multivariate regression analysis, sex (P = 0.007) and CVF (P < 0.001) were independently correlated with PER-E (all P-values were <0.05).ConclusionPatients with HOCM presented LA reverse remodeling. Impaired LA function was more common in female patients with HOCM due to their susceptibility to myocardial fibrosis.
| S-EPMC9748677 | biostudies-literature
Project description:BackgroundHypertrophic cardiomyopathy (HCM) is recognized as the most prevalent form of genetic cardiomyopathy, and recent investigations have shed light on the existence of sex disparities in terms of clinical presentation, disease progression, and outcomes.ObjectivesThis study aimed to systematically review the literature and perform a meta-analysis to comprehensively compare the clinical outcomes between female and male patients with HCM.MethodsA thorough search was conducted in databases including PubMed, Embase, Cochrane Library, and Web of Science, encompassing literature from inception until June 2023. The primary endpoints examined were: (1) all-cause mortality; (2) an arrhythmic endpoint comprising sudden cardiac death (SCD), sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and (3) a composite endpoint incorporating either (1) or (2), in addition to hospitalization for heart failure or cardiac transplantation. Pooled estimates were derived using a random-effects meta-analysis model.ResultsThe analysis encompassed a total of 29 observational studies, involving 44,677 patients diagnosed with HCM, of which 16,807 were female. Baseline characteristics revealed that the female group exhibited an advanced age [55.66 ± 0.04 years vs. 50.38 ± 0.03 years, pooled mean difference (MD) = 0.31, 95% CI: 0.22-0.40, p = 0.000, I2 = 88.89%], a higher proportion of New York Heart Association class III/IV patients [pooled odds ratio (OR) = 1.94, 95% CI: 1.55-2.43, p = 0.000, I2 = 85.92%], and a greater prevalence of left ventricular outflow tract gradient greater than or equal to 30 mmHg (pooled OR = 1.48, 95% CI: 1.27-1.73, p = 0.000, I2 = 68.88%) compared to the male group. The female group were more likely to have a positive genetic test (pooled OR = 1.27, 95% CI: 1.08-1.48, p = 0.000, I2 = 42.74%) and to carry the myosin heavy chain beta 7 mutation (pooled OR = 1.26, 95% CI: 1.04-1.54, p = 0.020, I2 = 0.00%) compared to the male group. Female sex exhibited a significant association with increased risks of all-cause mortality (pooled OR = 1.62, 95% CI: 1.38-1.89, p = 0.000, I2 = 72.78%) and the composite endpoint (pooled OR = 1.47, 95% CI: 1.20-1.79, p = 0.000, I2 = 84.96%), while no substantial difference was observed in the arrhythmic endpoint (pooled OR = 1.08, 95% CI: 0.87-1.34, p = 0.490, I2 = 55.48%).ConclusionsThe present findings suggest that female patients with HCM tend to experience poorer clinical outcomes. It is imperative to critically reevaluate disease definitions and enhance awareness to mitigate delays in the diagnosis and treatment of HCM in women, thereby fostering equitable healthcare practices.Systematic review registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023431881).
| S-EPMC10728470 | biostudies-literature
Project description:There is a paucity of research examining the molecular mechanisms underlying sex differences of clinical phenotypes and the prognosis in hypertrophic cardiomyopathy (HCM). The dataset GSE36961 was retrieved from Gene Expression Omnibus (GEO) database and comprehensive bioinformatics was employed to identify the core genes linked to sex differences in HCM patients. Additionally, gene set enrichment analysis (GSEA) was conducted to detect downstream signalling pathways. Furthermore, experimental validation was carried out using hearts from spontaneously hypertensive rats (SHRs). A comprehensive analysis revealed the identification of 208 differentially expressed genes (DEGs) in female patients with HCM with a notable downregulation of seven core genes. Notably, there were sex differences in the expression of ras dexamethasone-induced protein 1 (RASD1) and myosin 6 (MYH6) in HCM. Gene ontology (GO) analysis and GSEA demonstrated an enrichment of autophagy-related processes in disease progression in HCM females. Specifically, spearman's correlation analysis revealed a positive correlation between nicotinamide phosphoribosyl transferase (NAMPT) and RASD1 levels, particularly among female patients (R = 0.569, p < 0.001). Additionally, animal models confirmed that cardiac hypertrophy was more pronounced in SHR females compared to males. SHR females exhibited lower mRNA and protein expressions of RASD1 and NAMPT, which were associated with impaired autophagy. In this study, bioinformatics and validation using external data sets and animal models of left ventricular hypertrophy suggested that the RASD1/NAMPT axis is potentially a crucial mechanism underlying the elevated risk of cardiovascular disorders in HCM females, also pointing potentially prognostic biomarkers.
| S-EPMC11558267 | biostudies-literature
Project description:AimsTo describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes.Methods and resultsOur registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing-risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all-cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1-10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF.ConclusionsHypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.
| S-EPMC9288812 | biostudies-literature