Pub Date : 2026-01-07DOI: 10.1001/jamacardio.2025.4869
Neha Hafeez,Brian L Claggett,Anjali T Owens,Adam S Helms,Sara Saberi,Rachel Lampert,John C Stendahl,Euan A Ashley,Victoria N Parikh,Neal K Lakdawala,Jodie Ingles,Iacopo Olivotto,Carolyn Y Ho,Matthew R Taylor,Sadiya S Khan,Sharlene M Day
ImportanceArea-based indicators of social determinants of health (SDOH) are associated with higher risk for acquired heart disease, but their impact on conditions with a strong genetic etiology, such as hypertrophic cardiomyopathy (HCM), is not well understood.ObjectiveTo determine the association of area-based SDOH with clinical outcomes in patients with HCM.Design, Setting, and ParticipantsThis multicenter, prospective cohort study was conducted among US adult patients with HCM from 5 sites in the Sarcomeric Human Cardiomyopathy Registry (a multicenter prospective registry of patients with HCM) who were followed up for a median (IQR) period of 2.15 (0.15-5.82) years. Data were entered from 2015 to March 2024, and data analysis was completed from March 2024 to June 2025.ExposuresPatients' residential addresses were geocoded at the zip code level and linked to the American Communities Survey to estimate area-based (1) median household income and (2) social deprivation index (SDI), which ranges from 0 to 100, with higher scores indicating a more deprived area.Main Outcomes and MeasuresMultivariate models, adjusting for age at diagnosis, body mass index, hypertension, and sex, were used to estimate the independent association of area-based median household income and SDI with heart failure (HF), ventricular arrhythmias (VA), and an overall composite outcome (VA, HF, atrial fibrillation, stroke, and death).ResultsAmong 4431 US adult patients with HCM, median (IQR) age at HCM diagnosis was 51.3 (38.9-61.6) years, and 1862 patients (42.0%) were female. Median (IQR) area-based household income was $80 000 ($60 000-$110 000), and median (IQR) SDI was 25 (10-55). Adjusted hazard ratios comparing the lowest income group to the highest income group were 2.07 (95% CI, 1.77-2.42; P < .001) for HF, 1.31 (95% CI, 0.97-1.78; P = .08) for VA, and 1.52 (95% CI, 1.36-1.69; P < .001) for the overall composite outcome. Adjusted hazard ratios comparing the highest SDI (ie, more deprived) group to the lowest SDI group were 1.48 (95% CI, 1.29-1.70; P < .001) for HF, 1.55 (95% CI, 1.15-2.09; P = .004) for VA, and 1.36 (95% CI, 1.22-1.50; P < .001) for the overall composite outcome.Conclusions and RelevanceIn this multicenter cohort study, residing in an area with lower median household income or worse SDI were each independently associated with adverse clinical outcomes in patients with HCM. These findings suggest that despite the genetically determined nature of HCM, place of residence is associated with patient outcomes.
基于区域的健康社会决定因素指标（SDOH）与获得性心脏病的高风险相关，但它们对肥厚性心肌病（HCM）等具有强烈遗传病因的疾病的影响尚不清楚。目的探讨HCM患者区域性SDOH与临床预后的关系。设计、环境和参与者这项多中心、前瞻性队列研究在美国成年HCM患者中进行，这些患者来自肌性人类心肌病登记处（一个HCM患者的多中心前瞻性登记处）的5个地点，随访的中位（IQR）期为2.15（0.15-5.82）年。数据录入时间为2015年至2024年3月，数据分析时间为2024年3月至2025年6月。患者的居住地址按邮政编码进行地理编码，并与美国社区调查相关联，以估计基于区域的(1)家庭收入中位数和(2)社会剥夺指数（SDI），其范围从0到100，分数越高表明贫困程度越高。主要结局和测量采用多变量模型，调整诊断年龄、体重指数、高血压和性别，用于估计基于地区的家庭收入中位数和SDI与心力衰竭（HF）、室性心律失常（VA）和总体复合结局（VA、HF、房颤、中风和死亡）的独立关联。结果4431例美国成年HCM患者中，HCM诊断时的中位（IQR）年龄为51.3岁（38.9 ~ 61.6）岁，女性1862例（42.0%）。基于地区的家庭收入中位数（IQR）为80 000美元（60 000美元- 110 000美元），SDI中位数（IQR）为25（10-55）。最低收入组与最高收入组的校正风险比为2.07 （95% CI, 1.77-2.42; P < 0.05）。0.001), 1.31 (95% CI, 0.97-1.78；VA为1.52 (95% CI, 1.36-1.69; P <。001)的总体综合结果。最高SDI（即更贫困）组与最低SDI组的校正风险比为1.48 (95% CI, 1.29-1.70; P <。0.001), 1.55 (95% CI, 1.15-2.09；VA为1.36 (95% CI, 1.22-1.50; P <。001)的总体综合结果。结论和相关性在这项多中心队列研究中，居住在家庭收入中位数较低或SDI较差的地区与HCM患者的不良临床结果独立相关。这些发现表明，尽管HCM的性质由基因决定，但居住地与患者的预后有关。
{"title":"Social Determinants of Health and Clinical Outcomes in Hypertrophic Cardiomyopathy.","authors":"Neha Hafeez,Brian L Claggett,Anjali T Owens,Adam S Helms,Sara Saberi,Rachel Lampert,John C Stendahl,Euan A Ashley,Victoria N Parikh,Neal K Lakdawala,Jodie Ingles,Iacopo Olivotto,Carolyn Y Ho,Matthew R Taylor,Sadiya S Khan,Sharlene M Day","doi":"10.1001/jamacardio.2025.4869","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4869","url":null,"abstract":"ImportanceArea-based indicators of social determinants of health (SDOH) are associated with higher risk for acquired heart disease, but their impact on conditions with a strong genetic etiology, such as hypertrophic cardiomyopathy (HCM), is not well understood.ObjectiveTo determine the association of area-based SDOH with clinical outcomes in patients with HCM.Design, Setting, and ParticipantsThis multicenter, prospective cohort study was conducted among US adult patients with HCM from 5 sites in the Sarcomeric Human Cardiomyopathy Registry (a multicenter prospective registry of patients with HCM) who were followed up for a median (IQR) period of 2.15 (0.15-5.82) years. Data were entered from 2015 to March 2024, and data analysis was completed from March 2024 to June 2025.ExposuresPatients' residential addresses were geocoded at the zip code level and linked to the American Communities Survey to estimate area-based (1) median household income and (2) social deprivation index (SDI), which ranges from 0 to 100, with higher scores indicating a more deprived area.Main Outcomes and MeasuresMultivariate models, adjusting for age at diagnosis, body mass index, hypertension, and sex, were used to estimate the independent association of area-based median household income and SDI with heart failure (HF), ventricular arrhythmias (VA), and an overall composite outcome (VA, HF, atrial fibrillation, stroke, and death).ResultsAmong 4431 US adult patients with HCM, median (IQR) age at HCM diagnosis was 51.3 (38.9-61.6) years, and 1862 patients (42.0%) were female. Median (IQR) area-based household income was $80 000 ($60 000-$110 000), and median (IQR) SDI was 25 (10-55). Adjusted hazard ratios comparing the lowest income group to the highest income group were 2.07 (95% CI, 1.77-2.42; P < .001) for HF, 1.31 (95% CI, 0.97-1.78; P = .08) for VA, and 1.52 (95% CI, 1.36-1.69; P < .001) for the overall composite outcome. Adjusted hazard ratios comparing the highest SDI (ie, more deprived) group to the lowest SDI group were 1.48 (95% CI, 1.29-1.70; P < .001) for HF, 1.55 (95% CI, 1.15-2.09; P = .004) for VA, and 1.36 (95% CI, 1.22-1.50; P < .001) for the overall composite outcome.Conclusions and RelevanceIn this multicenter cohort study, residing in an area with lower median household income or worse SDI were each independently associated with adverse clinical outcomes in patients with HCM. These findings suggest that despite the genetically determined nature of HCM, place of residence is associated with patient outcomes.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"3 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImportanceHomozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)-directed therapies could reduce lipid levels through an LDLR-independent pathway.ObjectiveTo evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy.Design, Setting, and ParticipantsThis was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy.InterventionsPatients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up.Main Outcomes and MeasuresThe primary end point was the percent change in serum LDL-C level from baseline to week 12.ResultsA total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg/dL. At week 12, the mean percent change in LDL-C level was -59.09% (SD, 11.71%; 95% CI, -63.81% to -54.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of -61.32% for homozygous, -56.40% for compound heterozygous, and -72.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1).Conclusions and RelevanceResults show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT06009393.
{"title":"Anti-ANGPTL3 Antibody SHR-1918 for Homozygous Familial Hypercholesterolemia: A Nonrandomized Clinical Trial.","authors":"Daoquan Peng,Lvya Wang,Lin Pi,Yawei Xu,Jiyan Chen,Yanqing Wu,Nan Wang,Xiaoshu Chen,Sheng Qi,Sheng Feng,Gang Cheng,Chao Lv,Min Zhu,Ying Zhu","doi":"10.1001/jamacardio.2025.4878","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4878","url":null,"abstract":"ImportanceHomozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)-directed therapies could reduce lipid levels through an LDLR-independent pathway.ObjectiveTo evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy.Design, Setting, and ParticipantsThis was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy.InterventionsPatients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up.Main Outcomes and MeasuresThe primary end point was the percent change in serum LDL-C level from baseline to week 12.ResultsA total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg/dL. At week 12, the mean percent change in LDL-C level was -59.09% (SD, 11.71%; 95% CI, -63.81% to -54.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of -61.32% for homozygous, -56.40% for compound heterozygous, and -72.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1).Conclusions and RelevanceResults show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT06009393.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"76 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1001/jamacardio.2025.5043
Ask Tybjærg Nordestgaard,Daniel I Chasman,Vinayaga Moorthy,Jordan M Kraaijenhof,Nancy R Cook,I-Min Lee,Julie E Buring,Paul M Ridker
ImportanceElevated lipoprotein(a) predicts high risk of cardiovascular disease among a modest proportion of healthy individuals, an issue that complicates screening guidelines.ObjectiveTo examine spline models, clinical thresholds, and percentiles of baseline lipoprotein(a) levels as 30-year determinants of cardiovascular risk.Design, Setting, and ParticipantsThis cohort study was conducted among female health professionals participating in the Women's Health Study, who were followed up prospectively from 1993 to 2023. Women without cardiovascular disease, cancer, and other major chronic illnesses had blood samples taken at baseline. All individuals with lipoprotein(a) measurements and/or of European ancestry with genotype information for the LPA rs3798220 variation were included. Data analyses were performed from January through April 2025.ExposuresContinuously valued baseline lipoprotein(a), lipoprotein(a) clinical thresholds and percentiles, and LPA rs3798220 genotypes known to predict lipoprotein(a) levels among individuals of European ancestry.Main Outcomes and MeasuresThe primary outcomes were incident major cardiovascular events, coronary heart disease, ischemic stroke, and cardiovascular death. Age- and multivariable-adjusted cause-specific Cox models were used to calculated hazard ratios for the cardiovascular outcomes. The hypothesis was formulated after collection of the data.ResultsA total of 27 748 women with baseline lipoprotein(a) measurements and 23 279 women of European ancestry with rs3798220 genotype information were included (median [IQR] age, 53 [49-60] years), among whom 3707 and 3165 major cardiovascular events, respectively, accrued during a median (IQR) follow-up period of 27.8 (22.8-29.4) years. Among women with lipoprotein(a) measurements, lipoprotein(a) levels above 30 mg/dL or the 75th percentile (31 mg/dL) were associated with increased 30-year risk of major cardiovascular events and coronary heart disease. Levels above 120 mg/dL or the 99th percentile (131 mg/dL) were associated with increased risk of ischemic stroke and cardiovascular death. Multivariable adjusted hazard ratios for levels above 120 mg/dL vs below 10 mg/dL or above the 99th percentile vs below the 50th percentile (11 mg/dL) were 1.54 (95% CI, 1.24-1.92) and 1.74 (95% CI, 1.35-2.25) for major cardiovascular events, 1.80 (95% CI, 1.36-2.37) and 2.06 (95% CI, 1.49-2.84) for coronary heart disease, 1.41 (95% CI, 0.93-2.15) and 1.85 (95% CI, 1.17-2.93) for ischemic stroke, and 1.63 (95% CI, 1.16-2.28) and 1.86 (95% CI, 1.26-2.72) for cardiovascular death, respectively. Among women with genotype information, rs3798220 minor allele carriers had a higher risk of major cardiovascular events.Conclusions and RelevancePer the results of this cohort study, very high lipoprotein(a) levels correlated with increased 30-year risk of cardiovascular disease among healthy women. Screening for elevated lipoprotein(a) in the general population may be warranted.
{"title":"Thirty-Year Risk of Cardiovascular Disease Among Healthy Women According to Clinical Thresholds of Lipoprotein(a).","authors":"Ask Tybjærg Nordestgaard,Daniel I Chasman,Vinayaga Moorthy,Jordan M Kraaijenhof,Nancy R Cook,I-Min Lee,Julie E Buring,Paul M Ridker","doi":"10.1001/jamacardio.2025.5043","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5043","url":null,"abstract":"ImportanceElevated lipoprotein(a) predicts high risk of cardiovascular disease among a modest proportion of healthy individuals, an issue that complicates screening guidelines.ObjectiveTo examine spline models, clinical thresholds, and percentiles of baseline lipoprotein(a) levels as 30-year determinants of cardiovascular risk.Design, Setting, and ParticipantsThis cohort study was conducted among female health professionals participating in the Women's Health Study, who were followed up prospectively from 1993 to 2023. Women without cardiovascular disease, cancer, and other major chronic illnesses had blood samples taken at baseline. All individuals with lipoprotein(a) measurements and/or of European ancestry with genotype information for the LPA rs3798220 variation were included. Data analyses were performed from January through April 2025.ExposuresContinuously valued baseline lipoprotein(a), lipoprotein(a) clinical thresholds and percentiles, and LPA rs3798220 genotypes known to predict lipoprotein(a) levels among individuals of European ancestry.Main Outcomes and MeasuresThe primary outcomes were incident major cardiovascular events, coronary heart disease, ischemic stroke, and cardiovascular death. Age- and multivariable-adjusted cause-specific Cox models were used to calculated hazard ratios for the cardiovascular outcomes. The hypothesis was formulated after collection of the data.ResultsA total of 27 748 women with baseline lipoprotein(a) measurements and 23 279 women of European ancestry with rs3798220 genotype information were included (median [IQR] age, 53 [49-60] years), among whom 3707 and 3165 major cardiovascular events, respectively, accrued during a median (IQR) follow-up period of 27.8 (22.8-29.4) years. Among women with lipoprotein(a) measurements, lipoprotein(a) levels above 30 mg/dL or the 75th percentile (31 mg/dL) were associated with increased 30-year risk of major cardiovascular events and coronary heart disease. Levels above 120 mg/dL or the 99th percentile (131 mg/dL) were associated with increased risk of ischemic stroke and cardiovascular death. Multivariable adjusted hazard ratios for levels above 120 mg/dL vs below 10 mg/dL or above the 99th percentile vs below the 50th percentile (11 mg/dL) were 1.54 (95% CI, 1.24-1.92) and 1.74 (95% CI, 1.35-2.25) for major cardiovascular events, 1.80 (95% CI, 1.36-2.37) and 2.06 (95% CI, 1.49-2.84) for coronary heart disease, 1.41 (95% CI, 0.93-2.15) and 1.85 (95% CI, 1.17-2.93) for ischemic stroke, and 1.63 (95% CI, 1.16-2.28) and 1.86 (95% CI, 1.26-2.72) for cardiovascular death, respectively. Among women with genotype information, rs3798220 minor allele carriers had a higher risk of major cardiovascular events.Conclusions and RelevancePer the results of this cohort study, very high lipoprotein(a) levels correlated with increased 30-year risk of cardiovascular disease among healthy women. Screening for elevated lipoprotein(a) in the general population may be warranted.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"177 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1001/jamacardio.2025.5023
Paul W Armstrong,Christopher B Granger,Kevin R Bainey
{"title":"Transfer of Patients With ST-Elevation MI for Reperfusion-It's About Time.","authors":"Paul W Armstrong,Christopher B Granger,Kevin R Bainey","doi":"10.1001/jamacardio.2025.5023","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5023","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"42 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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