RESUMO
BACKGROUND: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. METHODS: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. RESULTS: Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). CONCLUSIONS: While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.
Assuntos
Biomarcadores , Negro ou Afro-Americano , Proteína C-Reativa , Insuficiência Cardíaca , Hospitalização , Humanos , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Incidência , Idoso , Biomarcadores/sangue , Hospitalização/estatística & dados numéricos , Adulto , Fatores de Risco , Mississippi/epidemiologia , Medição de Risco , Fatores de Tempo , Modelos de Riscos ProporcionaisRESUMO
Background Diabetes and hypertension have been associated with adverse left ventricular (LV) remodeling. While they often occur concurrently, their individual effects are understudied. We aimed to assess the independent effects of diabetes and hypertension on LV remodeling in Black adults. Methods and Results The JHS (Jackson Heart Study) participants (n=4143 Black adults) with echocardiographic measures from baseline exam were stratified into 4 groups: neither diabetes nor hypertension (n=1643), only diabetes (n=152), only hypertension (n=1669), or both diabetes and hypertension (n=679). Echocardiographic measures of LV structure and function among these groups were evaluated by multivariable regression adjusting for covariates. Mean age of the participants was 52±1 years, and 63.7% were women. LV mass index was not different in participants with only diabetes compared with participants with neither diabetes nor hypertension (P=0.8). LV mass index was 7.9% (6.0 g/m2) higher in participants with only hypertension and 10.8% (8.1 g/m2) higher in participants with both diabetes and hypertension compared with those with neither (P<0.001). LV wall thickness (relative, posterior, and septal) and brain natriuretic peptide levels in participants with only diabetes were not significantly higher than participants with neither (P>0.05). However, participants with both diabetes and hypertension demonstrated higher LV wall thickness and brain natriuretic peptide levels than participants with neither (P<0.05). Conclusions In this cross-sectional analysis, diabetes was not associated with altered LV structure or function in Black adults unless participants also had hypertension. Our findings suggest hypertension is the main contributor to cardiac structural and functional changes in Black adults with diabetes.
Assuntos
Diabetes Mellitus , Hipertensão , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Peptídeo Natriurético Encefálico , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Estudos Longitudinais , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Background Several cancer therapies have been associated with cardiovascular harm in early-phase clinical trials. However, some cardiovascular harms do not manifest until later-phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry-funded trials (69.2% versus 0.0%; P<0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P<0.001). Conclusions Our findings demonstrate significant under-representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later-phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , TroponinaRESUMO
OBJECTIVE: To evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life. METHODS: We evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m2 or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g. RESULTS: Among women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (-4.66 ml/min per 1.73 m2; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m2 (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes. CONCLUSION: A history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.
Assuntos
Hipertensão Induzida pela Gravidez/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Idoso , Causalidade , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade , Gravidez , Medição de Risco , Inquéritos e QuestionáriosRESUMO
Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self-reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000-2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1-19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow-up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39-3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0-1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose-response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88-3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2-fold increased risk of CHD over a median follow-up of greater than a decade.
Assuntos
Fumar Cigarros/epidemiologia , Doença da Artéria Coronariana , Calcificação Vascular , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/psicologia , Vasos Coronários/patologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Medição de Risco , Fumantes/estatística & dados numéricos , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologiaRESUMO
OBJECTIVE: To examine associations between physical activity (PA), inflammation, coronary artery calcification (CAC), and incident coronary heart disease (CHD) in African Americans. METHODS: Among Jackson Heart Study participants without prevalent CHD at baseline (n=4295), we examined the relationships between PA and high-sensitivity C-reactive protein, the presence of CAC (Agatston score ≥100), and incident CHD. Based on the American Heart Association's Life's Simple 7 metrics, participants were classified as having poor, intermediate, or ideal PA. RESULTS: After adjustment for possible confounding factors, ideal PA was associated with lower high-sensitivity C-reactive protein levels (ß, -0.15; 95% CI, -0.15 to -0.002) and a lower prevalence of CAC (odds ratio, 0.70; 95% CI, 0.51-0.96) compared with poor PA. During a median of 12.8 years of follow-up, there were 164 incident CHD events (3.3/1000 person-years). Ideal PA was associated with a lower rate of incident CHD compared with poor PA (hazard ratio, 0.55; 95% CI, 0.31-0.98). CONCLUSION: In a large community-based African American cohort, ideal PA was associated with lower inflammation levels, a lower prevalence of CAC, and a lower rate of incident CHD. These findings suggest that promotion of ideal PA may be an important way to reduce the risk of subclinical and future clinical CHD in African Americans.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doença da Artéria Coronariana/epidemiologia , Exercício Físico/fisiologia , Inflamação/epidemiologia , Medição de Risco/estatística & dados numéricos , Calcificação Vascular/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Multiple longitudinal responses together with time-to-event outcome are common in biomedical studies. There are several instances where the longitudinal responses are correlated with each other and at the same time each longitudinal response is associated with the survival outcome. The main purpose of this study is to present and explore a joint modeling approach for multiple correlated longitudinal responses and a survival outcome. The method will be illustrated using the Jackson Heart Study (JHS), which is one of the largest cardiovascular studies among African Americans. METHODS: Four longitudinal responses, i.e., total cholesterol (TC), high density lipoprotein (HDL) cholesterol, triglyceride (TG) and inflammation measured by high-sensitivity C-reactive protein (hsCRP); and time-to-coronary heart disease (CHD) were considered from the JHS. The repeated lipid and hsCRP measurements from a given subject overtime are likely correlated with each other and could influence the subject's risk for CHD. A joint modeling framework is considered. To deal with the high dimensionality due to the multiple longitudinal profiles, we use a pairwise bivariate model fitting approach that was developed in the context of multivariate Gaussian random effects models. The method is further explored through simulations. RESULTS: The proposed model performed well in terms of bias and relative efficiency. The JHS data analysis showed that lipid and hsCRP trajectories could exhibit interdependence in their joint evolution and have impact on CHD risk. CONCLUSIONS: We applied a unified and flexible joint modeling approach to analyze multiple correlated longitudinal responses and survival outcome. The method accounts for the correlation among the longitudinal responses as well as the association between each longitudinal response and the survival outcome at once. This helps to explore how the combination of multiple longitudinal trajectories could be related to the survival process.
Assuntos
Doença das Coronárias , HDL-Colesterol , Doença das Coronárias/epidemiologia , Humanos , Lipídeos , Estudos Longitudinais , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Hypertensive diseases in pregnancy have been associated with altered cardiac structure and function, yet these associations have not been systematically investigated in larger populations including African Americans. We evaluated the relationships between hypertensive diseases in pregnancy with cardiac structure and function later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. METHODS: We investigated 1013 African American women sibships with echocardiographic measurements from the GENOA study (Phase II, 2000-05; Jackson, MS). Women were classified as self-reported nulliparous (n = 61), a history of normotensive pregnancies (n = 780), a history of a hypertensive pregnancies (n = 152), or a history of preeclampsia (n = 20). We compared adjusted associations among these 4 groups with echocardiographic measurements of cardiac structure and function using generalized estimating equations, accounting for familial clustering. RESULTS: Among 1013 women with echocardiographic data (mean age 62 ± 9.5 years), women with a history of hypertensive pregnancy had lower left ventricular ejection fraction (LVEF) (P = 0.043) compared to nulliparous women and higher left atrial systolic dimension (LASD) compared to women with a history of normotensive pregnancies (P = 0.010), After adjusting for cardiovascular risk factors. There were no statistically significant differences in other echocardiographic parameters among these groups. CONCLUSIONS: A history of hypertension in pregnancy is associated with lower LVEF later in life, compared to nulliparous women and higher LASD compared to women with a history of normotensive pregnancies. However, given the multiple comparisons considered, this finding should be interpreted cautiously and requires further study.
Assuntos
Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Sodium-glucose cotransport protein-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce cardiovascular events in high-risk patients with type 2 diabetes mellitus (T2DM). We examined real-world use of these agents at a US academic medical center in the state of Mississippi. Prescriptions, provider specialty, and insurance status of users of SGLT2is and GLP-1RAs in patients with T2DM, and T2DM and cardiovascular disease (CVD) seen from 1st January 2013 to 30th June 2019 were obtained by electronic health records review. We identified 21,173 patients with T2DM and CVD. Overall, 306 (1.4%) and 349 (1.6%) patients received a SGLT2i and GLP-1RA, respectively. After the US Food and Drug Administration (FDA) expanded empagliflozin and liraglutide indications, a mean difference of 19.2 and 12.7 greater quarterly new prescriptions was noted, respectively, whereas no such rise in canagliflozin was observed. Primary care physicians accounted for 53.4% SGLT2i prescriptions, endocrinology for 30.3%, and cardiology for 6.0%. Primary care physicians accounted for 45.1% GLP-1RA prescriptions, endocrinology for 45.0%, and cardiology for 1.4%. Prescription patterns did not largely differ by patient insurance status. In conclusion, prescription of evidence-based therapies to improve CVD outcomes in high-risk patients with T2DM remains very low after several years of evidence generation. Low uptake was evident across insurance types. Modest increases in use were observed after regulatory expansions in labeling; however, cardiologists rarely engaged in prescription, underscoring the need for widespread implementation strategies across health care systems.
Assuntos
Centros Médicos Acadêmicos/tendências , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Aprovação de Drogas , Incretinas/uso terapêutico , Padrões de Prática Médica/tendências , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , United States Food and Drug Administration , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Uso de Medicamentos/tendências , Registros Eletrônicos de Saúde , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Incretinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Background Blacks are disproportionately affected by stroke compared with whites; however, less is known about the relationship between stroke and cigarette smoking in blacks. Therefore, we evaluated the relationship between cigarette smoking and all incident stroke in the JHS (Jackson Heart Study). Methods and Results JHS participants without a history of stroke (n=4410) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers at baseline (2000-2004). Current smokers were further classified by smoking intensity (number of cigarettes smoked per day [1-19 and ≥20]) and followed up for incident stroke (through 2015). Hazard ratios (HRs) for incident stroke for current and past smoking compared with never smoking were estimated with adjusted Cox proportional hazard regression models. After adjusting for cardiovascular risk factors, the risk for stroke in current smokers was significantly higher compared with never smokers (HR, 2.48; 95% CI, 1.60-3.83) but there was no significant difference between past smokers and never smokers (HR, 1.10; 95% CI, 0.74-1.64). There was a dose-dependent increased risk of stroke with smoking intensity (HR, 2.28 [95% CI, 1.38-3.86] and HR, 2.78 [95% CI, 1.47-5.28] for current smokers smoking 1-19 and ≥20 cigarettes/day, respectively). Conclusions In a large cohort of blacks, current cigarette smoking was associated with a dose-dependent higher risk of all stroke. In addition, past smokers did not have a significantly increased risk of all stroke compared with never smokers, which suggests that smoking cessation may have potential benefits in reducing the incidence of stroke in blacks.