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1.
Nat Commun ; 13(1): 3549, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729114

RESUMO

In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called "PRSsum", forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.

3.
Circulation ; 145(18): e869-e871, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35500047

Assuntos
Encéfalo , Humanos
4.
J Am Coll Cardiol ; 79(19): 1873-1886, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35550683

RESUMO

BACKGROUND: Coronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years. OBJECTIVES: The purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years. METHODS: We harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques. RESULTS: The prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile. CONCLUSIONS: In a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Calcificação Vascular , Adulto , Cálcio , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Adulto Jovem
5.
Circulation ; 145(23): e1059-e1071, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35531777

RESUMO

Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association's commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.


Assuntos
American Heart Association , Doenças Cardiovasculares , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Feminino , Acesso aos Serviços de Saúde , Humanos , Estados Unidos/epidemiologia
6.
Aging Cell ; 21(6): e13608, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35546478

RESUMO

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10-7 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, PMR  = 4.1 × 10-4 ) and negatively associated with longevity (Beta = -1.9, PMR  = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.


Assuntos
Doenças Cardiovasculares , Neoplasias , Biomarcadores , Doenças Cardiovasculares/genética , Metilação de DNA/genética , Epigênese Genética , Epigenômica , Humanos , Masculino , Neoplasias/genética
7.
J Am Heart Assoc ; 11(11): e025050, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35583146

RESUMO

Background Adverse pregnancy outcomes (APOs) (hypertensive disorders of pregnancy [HDP], preterm delivery [PTD], or low birth weight [LBW]) are associated adverse maternal and offspring cardiovascular outcomes. Therefore, we sought to describe nationwide temporal trends in the burden of each APO (HDP, PTD, LBW) from 2007 to 2019 to inform strategies to optimize maternal and offspring health outcomes. Methods and Results We performed a serial cross-sectional analysis of APO subtypes (HDP, PTD, LBW) from 2007 to 2019. We included maternal data from all live births that occurred in the United States using the National Center for Health Statistics Natality Files. We quantified age-standardized and age-specific rates of APOs per 1000 live births and their respective mean annual percentage change. All analyses were stratified by self-report of maternal race and ethnicity. Among 51 685 525 live births included, 15% were to non-Hispanic Black individuals, 24% Hispanic individuals, and 6% Asian individuals. Between 2007 and 2019, age standardized HDP rates approximately doubled, from 38.4 (38.2-38.6) to 77.8 (77.5-78.1) per 1000 live births. A significant inflection point was observed in 2014, with an acceleration in the rate of increase of HDP from 2007 to 2014 (+4.1% per year [3.6-4.7]) to 2014 to 2019 (+9.1% per year [8.1-10.1]). Rates of PTD and LBW increased significantly when co-occurring in the same pregnancy with HDP. Absolute rates of APOs were higher in non-Hispanic Black individuals and in older age groups. However, similar relative increases were seen across all age,racial and ethnic groups. Conclusions In aggregate, APOs now complicate nearly 1 in 5 live births. Incidence of HDP has increased significantly between 2007 and 2019 and contributed to the reversal of favorable trends in PTD and LBW. Similar patterns were observed in all age groups, suggesting that increasing maternal age at pregnancy does not account for these trends. Black-White disparities persisted throughout the study period.


Assuntos
Resultado da Gravidez , Nascimento Prematuro , Idoso , Estudos Transversais , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estados Unidos/epidemiologia
8.
Circulation ; : 101161CIRCULATIONAHA121058311, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35607988

RESUMO

BACKGROUND: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated. METHODS: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the ß estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD. RESULTS: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th-75th percentile, 33.7-34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71-3.49], Black men: HR, 1.59 [1.20-2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55-1.52], Black men: HR 1.02 [0.70-1.49]). In women, the largest magnitude percent reduction in the ß estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the ß estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors. CONCLUSIONS: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men.

9.
Circ Heart Fail ; 15(5): e009229, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35477292

RESUMO

BACKGROUND: Multisociety guidelines recommend a goal systolic blood pressure (BP) <130 mm Hg and a hemoglobin A1c (HbA1c) <8% in patients with heart failure (HF), regardless of ejection fraction. Few studies have described BP and glycemic control in ambulatory patients with HF and racial and ethnic disparities in this subset of the population. METHODS: We evaluated prevalence of uncontrolled BP and HbA1c in non-Hispanic Black, non-Hispanic White, and Mexican American adults aged ≥20 years with self-reported HF (National Health and Nutrition Examination Surveys: 2001-2018). Prevalence ratios (95% CI) for uncontrolled BP and HbA1c were calculated by race and ethnicity and adjusted for sex, age, treatment, and socioeconomic status. In secondary analyses, we examined trends in the prevalence of uncontrolled BP and HbA1c. RESULTS: Uncontrolled BP was present in 48% (95% CI, 49%-56%) of adults with HF (representing 2.3 million people). Non-Hispanic Black participants had a higher prevalence of uncontrolled BP compared with non-Hispanic White participants (53% [48%-58%] compared with 47% [43%-51%], P<0.05). In adjusted models, non-Hispanic Black participants were 1.19 (1.02-1.39) times more likely to have uncontrolled BP than non-Hispanic White participants. Overall, uncontrolled HbA1c was found in 8% (6%, 10%) with no differences by race and ethnicity. Prevalence of uncontrolled BP improved over time but uncontrolled risk factors remained high-2017 to 2018: 41% (36%, 47%) and 7% (5%, 12%) had uncontrolled BP and HbA1c, respectively. CONCLUSIONS: We document an unacceptably high prevalence of uncontrolled BP and HbA1c in a nationally representative, ambulatory HF sample with significant differences in BP control by race and ethnicity.


Assuntos
Insuficiência Cardíaca , Adulto , Pressão Sanguínea , Estudos Transversais , Hemoglobina A Glicada , Controle Glicêmico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Inquéritos Nutricionais , Estados Unidos/epidemiologia
10.
BMC Cardiovasc Disord ; 22(1): 139, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365073

RESUMO

BACKGROUND: Ideal "cardiovascular health" (CVH)-optimal diet, exercise, nonsmoking, BMI, BP, lipids, and glucose-is associated with healthy longevity in adults. Pediatric heart transplant (HT) patients may be at risk for suboptimal CVH. METHODS: Single-center retrospective study of HT patients 2003-2014 who survived 1 year post-transplant. Five CVH metrics were collected at listing, 1, 3 and 5 years post-transplant (diet and exercise were unavailable). CVH was scored by summing individual metrics: ideal = 2, intermediate = 1, and poor = 0 points; total scores of 8-10 points were considered high (favorable). CVH was compared between HT patients and the US pediatric population (GP) utilizing NHANES 2007-2016. Logistic regression was performed to examine the association of CVH 1 year post-transplant with a composite adverse outcome (death, re-listing, coronary vasculopathy, or chronic kidney disease) 3 years post-transplant. RESULTS: We included 110 HT patients (median age at HT: 6 years [range 0.1-21]) and 19,081 NHANES participants. CVH scores among HT patients were generally high at listing (75%), 1 (74%), 3 (87%) and 5 (76%) years post-transplant and similar to GP, but some metrics (e.g., glucose) were worse among HT patients. Among HT patients, CVH was poorer with older age and non-Caucasian race/ethnicity. Per 1-point higher CVH score, the demographic-adjusted OR for adverse outcomes was 0.95 (95% CI, 0.7-1.4). CONCLUSIONS: HT patients had generally favorable CVH, but some metrics were unfavorable and CVH varied by age and race/ethnicity. No significant association was detected between CVH and adverse outcomes in this small sample, but study in a larger sample is warranted.


Assuntos
Doenças Cardiovasculares , Transplante de Coração , Adolescente , Adulto , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Transplante de Coração/efeitos adversos , Humanos , Lactente , Inquéritos Nutricionais , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Sci Adv ; 8(14): eabl6579, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35385311

RESUMO

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

13.
JAMA Cardiol ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35471450
17.
Nat Genet ; 54(3): 263-273, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35256806

RESUMO

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease.


Assuntos
Estudo de Associação Genômica Ampla , Herança Multifatorial , Alelos , Estudo de Associação Genômica Ampla/métodos , Humanos , Desequilíbrio de Ligação , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética
18.
JAMA Netw Open ; 5(3): e222318, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35289856

RESUMO

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P < .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95% CI, $10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to $28 319]) participants compared with those with a normal BMI (P < .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife.


Assuntos
Longevidade , Medicare , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Humanos , Masculino , Morbidade , Estudos Prospectivos , Estados Unidos/epidemiologia
19.
Am J Hypertens ; 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303061

RESUMO

BACKGROUND: We pooled ambulatory blood pressure monitoring data from five US studies, including the Jackson Heart Study (JHS), the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Masked Hypertension Study, the Improving the Detection of Hypertension Study, and the North Carolina Masked Hypertension Study. Using a cross-sectional study design, we estimated differences in the prevalence of masked hypertension by race/ethnicity when out-of-office BP included awake, asleep, and 24-hour BP versus awake BP alone. METHODS: We restricted the analyses to participants with office systolic BP (SBP) < 130 mmHg and diastolic BP (DBP) < 80 mmHg. High awake BP was defined as mean SBP/DBP ≥130/80 mmHg, high asleep BP as mean SBP/DBP ≥110/65 mmHg and high 24-hour BP as mean SBP/DBP ≥125/75 mmHg. RESULTS: Among participants not taking antihypertensive medication (n=1,292), the prevalence of masked hypertension with out-of-office BP defined by awake BP alone or by awake, asleep or 24-hour BP was 34.5% and 48.7%, respectively, among non-Hispanic White, 39.7% and 67.6% among non-Hispanic Black, and 19.4% and 35.1% among Hispanic participants. After multivariable adjustment, non-Hispanic Black were more likely than non-Hispanic White participants to have masked hypertension by asleep or 24-hour BP but not awake BP (adjusted odds ratio 2.14 95%CI 1.45-3.15) and by asleep or 24-hour BP and awake BP (OR 1.61; 95%CI 1.12-2.32) versus not having masked hypertension. CONCLUSION: Assessing asleep and 24-hour BP measures increases the prevalence of masked hypertension more among non-Hispanic Black versus non-Hispanic White individuals.

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