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1.
Diabetes ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820761

RESUMO

DNA methylation-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D, in the context of their relationships with obesity.A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups; normal weight, overweight, and obese. A one-year increase of GrimAge was associated with higher 10-year (Y15 to Y25) incidence of T2D (OR=1.06, 95% CI=1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (Positive GrimAA; having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR=2.57, 95% CI=1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%).In conclusion, both older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. Our findings suggest that epigenetic age measurements with DNA methylation can potentially be utilized as a risk factor or biomarker associated with T2D development.

2.
Nat Commun ; 11(1): 6285, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293549

RESUMO

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

3.
Ethn Health ; : 1-13, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33222499

RESUMO

OBJECTIVE: Variability of Cardiovascular disease (CVD) risk, including racial difference, is not fully accounted for by the variability of traditional CVD risk factors. We used a multiple biomarker model as a framework to explore known racial differences in CVD burden. DESIGN: We measured associations between accelerated aging (AccA) measured by a combination of biomarkers, and cardiovascular morbidity and all-cause mortality using data from the Coronary Artery Risk Development in Young Adults study (CARDIA). AccA was defined as the difference between biological age, calculated using biomarkers with the Klemera and Doubal method, and chronological age. Using logistic regression, we assessed overall and race-specific associations between AccA, CVD, and all-cause mortality. RESULTS: Among our cohort of 2959 Black or White middle-aged adults, after adjustment, a one-year increase in AccA was associated with increased odds of CVD (Odds Ratio (OR) = 1.04; 95% CI: 1.02, 1.06), stroke (OR = 1.12; 95% CI: 1.07, 1.17), and all-cause mortality (OR = 1.05; 95% CI: 1.02, 1.08). We did not find significant overall racial differences, but we did find race by sex differences where Black men differed markedly from White men in the strength of association with CVD (OR = 1.06, 95% CI: 1.01, 1.12). CONCLUSIONS: We provide evidence that AccA is associated with future CVD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33212181

RESUMO

BACKGROUND: Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B-defining LV abnormalities over 25 years, independent of cumulative risk factor burden. METHODS: We analyzed data from the Coronary Artery Risk Development in Young Adults Study. Participants (N=2,833) were 45% black, 56% female, with mean baseline age 30.1 years. We used generalized estimating equation logistic regression to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk-factor-adjusted associations between baseline LV parameters and incident abnormalities. We used Cox regression to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years' follow-up. RESULTS: Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4-11.8%) and 45.0% (42.0-48.1%), with significant race-sex disparities; e.g., at age 60: black men 52.7% (44.9-60.3%), black women 59.4% (53.6-65.0%), white men 39.1% (33.4-45.0%), and white women 39.1% (33.9-44.6%). Over 25 years, baseline LV end-systolic dimension/height was associated with incident systolic dysfunction (adjusted odds ratio per 1-SD higher: 2.56 [1.87-3.52]), eccentric hypertrophy (1.34 [1.02-1.75]), concentric hypertrophy (0.69 [0.51-0.91]), and concentric remodeling (0.68 [0.58-0.79]); baseline LV mass/height2.7 was associated with incident eccentric hypertrophy (1.70 [1.25-2.32]), concentric hypertrophy (1.63 [1.19-2.24]), and diastolic dysfunction (1.24 [1.01-1.52]). Among the entire cohort with baseline echocardiographic data available (N=4097; 72 HF events), LV end-systolic dimension/height and mass/height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1-SD higher: 1.56 [95% CI, 1.26-1.93] and 1.42 [1.14-1.75], respectively). CONCLUSIONS: Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.

5.
Diabetes Res Clin Pract ; 166: 108334, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32702469

RESUMO

AIMS: To assess sex differences in cardiovascular (CVD) risk factor changes before and after the development of type 2 diabetes, and, the association between incident diabetes with incident CVD in mid-life. METHODS: We included 4893 Coronary Artery Risk Development in Young Adults Study participants, age 18-30 years at enrollment (1985-86). We ascertained incident diabetes and assessed sex differences in annual change in body mass index, blood pressure, and lipids before and after the ascertainment of diabetes using piecewise linear regression. We examined sex differences in the association between incident diabetes with incident CVD over 31 years of median follow-up. RESULTS: Progression in most CVD risk factors did not differ by sex before diabetes. Women had better CVD profiles at the time of diabetes compared to men, and after diabetes, women had worse annual changes in blood pressure and lipids. Incident diabetes was associated with a higher hazard for incident CVD (Hazard Ratio [HR]: 1.45, 95% confidence limits: 1.07, 1.96) and we did not observe effect modification by sex (p for interaction = 0.8). CONCLUSIONS: CVD risk factors worsened more rapidly after the development of type 2 diabetes for women than men. However, diabetes was not a stronger risk factor for incident CVD for women than men.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Adolescente , Adulto , Idade de Início , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Caracteres Sexuais , Fatores de Tempo , Adulto Jovem
6.
Circ Genom Precis Med ; 13(4): e002772, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32510982

RESUMO

BACKGROUND: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. METHODS: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. RESULTS: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (P=6.65×10-6 for the interaction test) and replicated at nominal significance level (P=0.013) in SMC5. CONCLUSIONS: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.

7.
Hypertension ; 76(2): 404-409, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32594795

RESUMO

Recent evidence links long-term (visit-to-visit) blood pressure (BP) variability to the risk of cardiovascular disease, independent of mean BP levels. Potential associations between long-term BP variability and cardiovascular disease risk may be reflected in early life course alterations in coronary artery calcium (CAC) and carotid intima-media thickness. We evaluated 2482 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean [SD] age at the year 20 exam [2005-2006] was 45.4 [3.6] years, 43.2% men, and 41.3% black). We included participants with BP assessments across 20-years (year 0, 2, 5, 7, 10, 15, 20 exams) and carotid intima-media thickness and CAC data at the year 20 exam. BP variability was assessed using variability independent of the mean and SD. Adjusted multivariable linear or logistic regression models (as appropriate) were used to assess associations between long-term BP variability measures and carotid intima-media thickness. and CAC (ln [CAC+1] and prevalent CAC). Long-term systolic BP variability independent of the mean (per 1 SD) was positively associated with carotid intima-media thickness (ß=10 µm, SE=3, P=0.002). Similarly, long-term diastolic BP variability independent of the mean was associated with carotid intima-media thickness (ß=10 µm, SE (3), P=0.001). Long-term BP variability was not associated with either ln [CAC+1] or prevalent CAC. Long-term systolic and diastolic BP variability across early adulthood was positively associated with modest adverse midlife alterations in carotid intima-media thickness but not to CAC. Our findings provide further insights into pathophysiologic mechanisms that link long-term BP variability to cardiovascular disease.

8.
Health Place ; 62: 102286, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32479363

RESUMO

Although racial residential segregation and interpersonal racial discrimination are associated with cardiovascular disease, few studies have examined their link with diabetes risk or management. We used longitudinal data from 2,175 black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine associations of racial residential segregation (Gi* statistic) and experiences of racial discrimination with diabetes incidence and management. Multivariable Cox models estimated associations for incident diabetes and GEE logistic regression estimated associations with diabetes management (meeting targets for HbA1c, systolic blood pressure, and LDL cholesterol). Neither segregation nor discrimination were associated with diabetes incidence or management.

9.
ESC Heart Fail ; 7(4): 1510-1519, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32449612

RESUMO

AIMS: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. METHODS AND RESULTS: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.30%, P < 0.05; ß = -0.35%, P < 0.05; ß = -0.32%, P < 0.05; ß = -0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.29, P < 0.05; ß = -0.38, P < 0.01; ß = -0.20, P > .05; and ß = -0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (ß = -1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). CONCLUSIONS: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

10.
Med Sci Sports Exerc ; 52(6): 1314-1321, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32427750

RESUMO

PURPOSE: We evaluated the associations between accelerometer-estimated physical activity (PA) intensity and heart rate variability (HRV) and examined mediation of these associations by glycemic control indices and other cardiovascular disease risk factors. METHODS: Data were from 1668 participants (X[Combining Overline]age = 45.9 ± 3.5 yr, 58.0% female, 39.9% black) who participated in year 20 (2005-2006) of the Coronary Artery Risk Development in Young Adults Fitness Study. The ActiGraph 7164 estimated participants' mean minutes per day of vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) over 7 d. Three sequential 10-s 12-lead ECG strips were used to derive standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Mediators representing glycemic control indices included fasting glucose, fasting insulin, and 2-h oral glucose tolerance, with other mediators being traditional cardiovascular disease risk factors. Multiple linear regression assessed independent associations of PA intensity with HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV association attributable to physiological mediators. RESULTS: Participants averaged 2.7 ± 6.2 min·d, 33.0 ± 22.0 min·d, and 360.2 ± 83.8 min·d of VPA, MPA, and LPA, respectively, with mean values for SDNN (32.6 ± 22.4 ms) and rMSSD (34.0 ± 24.8 ms) similar. After adjustment for demographic and lifestyle behaviors, VPA was associated with both HRV metrics (SDNN: std beta = 0.06 [0.03, 0.10]; rMSSD: std beta = 0.08 [0.05, 0.12]) and LPA with rMSSD only (std beta = 0.05 [0.01, 0.08]). Fasting insulin and glucose mediated 11.6% to 20.7% of the association of VPA and LPA with HRV, with triglycerides also potentially mediating these associations (range, 9.6%-13.4%). CONCLUSIONS: Accelerometer-estimated VPA was associated with higher (i.e., improved) HRV. Light-intensity PA also demonstrated a positive association. Mediation analyses suggested these associations may be most attributable to glucose-insulin dynamics.


Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares/fisiopatologia , Exercício Físico/fisiologia , Frequência Cardíaca , Actigrafia/instrumentação , Adulto , Sistema Nervoso Autônomo/fisiologia , Glicemia/metabolismo , Doenças Cardiovasculares/prevenção & controle , Feminino , Monitores de Aptidão Física , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
J Am Soc Echocardiogr ; 33(7): 878-887.e3, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32336609

RESUMO

BACKGROUND: The relationship between long-term obesity and left atrial (LA) structure and function is not entirely understood. We examined the association of cumulative body mass index (cBMI) with LA remodeling using three-dimensional (3D) speckle-tracking echocardiography (STE). METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a community-based cohort of black and white, men and women, ages 18-30 years at baseline in 1985-86 from four U.S. centers. This study included 2,144 participants who had satisfactory image quality and body mass index measurements during the entire follow-up period. The 3D STE-derived LA parameters were maximum, minimum, and pretrial contraction volumes; total, passive, and active emptying fraction; maximum systolic longitudinal strain; and early and late diastolic longitudinal strain rates. Multivariable linear regression analyses stratified by sex assessed the relationship between cBMI and 3D STE-derived LA parameters, adjusting for demographics and traditional cardiovascular. RESULTS: The mean age of the cohort was 55 ± 3.6 years; 54.8% were women, and 46.5% were black. There were statistically significant additive sex interactions for the association between cBMI and LA minimum contraction value, maximum systolic longitudinal strain, and early and late diastolic longitudinal strain rates. In the fully adjusted model, greater cBMI was associated with lower magnitude LA longitudinal deformation (maximum systolic longitudinal strain and early and late diastolic longitudinal strain rates) in men and with higher LA emptying fraction in women. In addition, greater cBMI was associated with higher LA phasic volumes indices in both men and women. CONCLUSIONS: This study showed that while greater cBMI from early adulthood throughout middle age was associated with higher LA volumes in both genders, differences were found for LA function, with lower longitudinal deformation in men and higher reservoir and active LA function in women.

12.
JAMA Cardiol ; 5(7): 795-801, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293640

RESUMO

Importance: Long-term blood pressure (BP) variability has emerged as a reproducible measure that is associated with heart failure independent of systemic BP. Visit-to-visit BP variability may be associated with the risk of heart failure early in the life course and thus may be reflected in subclinical alterations in cardiac structure and function. Objective: To evaluate the association between visit-to-visit BP variability in early adulthood and myocardial structure and function in middle age. Design, Setting, and Participants: This cohort study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based cohort study of 5115 participants aged 18 to 30 years at baseline (year 0; March 25, 1985, to June 7, 1986) and followed up over a 30-year interval. A total of 2400 CARDIA study participants underwent evaluation at 4 field sites (Birmingham, Alabama; Oakland, California; Chicago, Illinois; and Minneapolis, Minnesota). Blood pressure was measured at 8 visits over a 25-year interval and participants received echocardiograms at year 25 (June 1, 2010, to August 31, 2011). Data analysis was conducted from June 7, 1986, to August 31, 2011. Exposures: Visit-to-visit systolic and diastolic BP variability measures included SD, average real variability, and variability independent of the mean. Main Outcomes and Measures: Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 25 examination. Results: Of the 2400 participants, 1024 were men (42.7%) and 976 were African American (40.7%); mean (SD) age at the year 25 examination was 50.4 (3.6) years. Per 1-SD increment, greater visit-to-visit systolic BP variability independent of the mean was associated with higher left-ventricular (LV) mass index (ß [SE], 2.66 [0.4] g/m2, P < .001), worse diastolic function (early peak diastolic mitral annular velocity [é]) (ß [SE], -0.40 [0.1] cm/s, P < .001), higher LV filling pressures (mitral inflow velocity to early diastolic mitral annular velocity [E/é]) ß [SE], 0.37 [0.1] cm/s, P < .001), and worse global longitudinal strain (ß [SE], 0.17 [0.1], P = .002). Similarly, greater visit-to-visit diastolic BP variability was associated with higher LV mass index (ß [SE], 3.21 [0.5] g/m2, P < .001), worse diastolic function (é: ß [SE], -0.24 [0.1] cm/s [P < .001]; E/é: ß [SE], 0.23 [0.1] cm/s [P < .001]), and worse global longitudinal strain (ß [SE], 0.13 [0.1], P = .02). The findings remained consistent when other BP variability measures were used (SD and average real variability). Conclusions and Relevance: In this cohort study using data from the CARDIA study, greater visit-to-visit systolic and diastolic BP variability have been associated with adverse alterations in cardiac structure as well as systolic and diastolic function independent of mean BP levels.

13.
Eur J Prev Cardiol ; : 2047487320915342, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276575

RESUMO

AIMS: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear. METHODS AND RESULTS: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001). CONCLUSIONS: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

14.
Open Heart ; 7(1): e001270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201592

RESUMO

Objective: To evaluate the association of cigarette smoking and right ventricular (RV) systolic and diastolic functions in a population-based cohort of individuals at middle age. Methods: This cross-sectional study included participants who answered the smoking questionnaire and underwent echocardiography at the Coronary Artery Risk Development in Young Adulthood year 25 examination. RV systolic function was assessed by echocardiographic-derived tricuspid annular plane systolic excursion (TAPSE) and by right ventricular peak systolic velocity (RVS'), while RV diastolic function was evaluated by early right ventricular tissue velocity (RVE'). Multivariable linear regression models assessed the relationship of smoking with RV function, adjusting for age, sex, race, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, diabetes mellitus, alcohol consumption, pulmonary function, left ventricular systolic and diastolic function and coronary artery calcium score. Results: A total of 3424 participants were included. The mean age was 50±4 years; 57% were female; and 53% were black. There were 2106 (61%) never smokers, 750 (22%) former smokers and 589 (17%) current smokers. In the multivariable analysis, current smokers had significantly lower TAPSE (ß=-0.082, SE=0.031, p=0.008), RVS' (ß=-0.343, SE=0.156, p=0.028) and RVE' (ß=-0.715, SE=0.195, p<0.001) compared with never smokers. Former smokers had a significantly lower RVE' compared with never smokers (ß=-0.414, SE=0.162, p=0.011), whereas no significant difference in RV systolic function was found between former smokers and never smokers. Conclusions: In a large multicenter community-based biracial cohort of middle-aged individuals, smoking was independently related to both worse RV systolic and diastolic functions.

15.
Am J Med ; 133(8): 946-953, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32001229

RESUMO

BACKGROUND: The prognostic significance of temporal changes in resting heart rate in young adults for premature heart failure and cardiovascular disease is unclear. We investigated the association between temporal changes in resting heart rate in young adults and early adult risk factors, subsequent cardiac function, and the risk of heart failure and cardiovascular by middle age. METHODS: We examined 4343 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean [SD] age was 29.9 [3.6] years at the CARDIA Year-5 examination [1990-1991], 49% of participants were men, and 45% were African-American). Adjusted linear regression models were used to assess the association between temporal changes in resting heart rate, early life cardiovascular disease risk factors, and midlife cardiac function. Cox proportional hazard regression models were used to relate temporal changes in resting heart rate to heart failure and cardiovascular disease. Outcomes were followed up until August 31, 2017. RESULTS: Higher alcohol consumption (ß = 0.03, P <0.001), lower physical activity (ß = 0.002, P = 001), smoking (ß = 1.58, P <0.001), men (P <0.001), African Americans (P <0.001), impaired left ventricular relaxation (e´,ß = -0.13, P = 0.002), and worse diastolic function (E/e´, ß = 0.1, P = 0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio [HR] =1.37 95% confidence interval [CI] [1.05-1.79] and HR = 1.38 95% CI [1.02-1.86]) and a higher risk cardiovascular disease (HR = 1.23 95% CI [1.07-1.42] and HR = 1.23 95% CI [1.05-1.44]). CONCLUSIONS: Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by midlife. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.


Assuntos
Insuficiência Cardíaca/epidemiologia , Frequência Cardíaca/fisiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Afro-Americanos , Consumo de Bebidas Alcoólicas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Ecocardiografia , Grupo com Ancestrais do Continente Europeu , Exercício Físico , Feminino , Insuficiência Cardíaca/etnologia , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Descanso , Fatores de Risco , Comportamento Sedentário , Fatores Sexuais , Fumar/epidemiologia , Fatores de Tempo , Estados Unidos/epidemiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
16.
J Biomed Inform ; 103: 103379, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32001388

RESUMO

The presence of missing data at the time of prediction limits the application of risk models in clinical and research settings. Common ways of handling missing data at the time of prediction include measuring the missing value and employing statistical methods. Measuring missing value incurs additional cost, whereas previously reported statistical methods results in reduced performance compared to when all variables are measured. To tackle these challenges, we introduce a new strategy, the MMTOP algorithm (Multiple models for Missing values at Time Of Prediction), which does not require measuring additional data elements or data imputation. Specifically, at model construction time, the MMTOP constructs multiple predictively equivalent risk models utilizing different risk factor sets. The collection of models are stored and to be queried at prediction time. To predict an individual's risk in the presence of incomplete data, the MMTOP selects the risk model based on measurement availability for that individual from the collection of predictively equivalent models and makes the risk prediction with the selected model. We illustrate the MMTOP with severe hypoglycemia (SH) risk prediction based on data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. We identified 77 predictively equivalent models for SH with cross-validated c-index of 0.77 ± 0.03. These models are based on 77 distinct risk factor sets containing 12-17 risk factors. In terms of handling missing data at the time of prediction, the MMTOP outperforms all four tested competitor methods and maintains consistent performance as the number of missing variables increase.

17.
J Gerontol A Biol Sci Med Sci ; 75(2): 380-386, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-30796828

RESUMO

BACKGROUND: We investigated whether carotid intima-media thickness is associated with measures of cerebral blood flow (CBF), white matter hyperintensities, and brain volume in a biracial cohort of middle-aged individuals. METHODS: We performed a cross-sectional cohort study based on data from a multicenter, population-based study Coronary Artery Risk Development in Young Adults. Using linear and logistic regression, we estimated the association of the composite intima-media thickness measured in three segments of carotid arteries (common carotid artery, carotid artery bulb, and internal carotid artery) with volume (cm3) and CBF (mL/100 g/min) in the total brain and gray matter as well as volume of white matter hyperintensities (cm3). RESULTS: In the analysis, 461 participants (54% women, 34% African Americans) were included. Greater intima-media thickness was associated with lower CBF in gray matter (ß=-1.36; p = .04) and total brain (ß=-1.26; p = .04), adjusting for age, sex, race, education, and total brain volume. The associations became statistically nonsignificant after further controlling for cardiovascular risk factors. Intima-media thickness was not associated with volumes of total brain, gray matter, and white matter hyperintensities. CONCLUSIONS: This study suggests that lower CBF in middle age is associated with markers of atherosclerosis in the carotid arteries. This association may reflect early long-term exposure to traditional cardiovascular risk factors. Early intervention on atherosclerotic risk factors may modulate the trajectory of CBF as people age and develop brain pathology.


Assuntos
Encéfalo/diagnóstico por imagem , Espessura Intima-Media Carotídea , Circulação Cerebrovascular , Imagem por Ressonância Magnética , Afro-Americanos/estatística & dados numéricos , Estudos Transversais , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estados Unidos , Substância Branca/diagnóstico por imagem
18.
J Vet Intern Med ; 33(5): 2090-2095, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31471926

RESUMO

BACKGROUND: Positive health implications of early recognition of calcium oxalate (CaOx) urolithiasis include increased opportunity for nonsurgical removal, early dietary modification to minimize urolith growth, early removal to avoid urinary obstruction, and early recognition of genetic and metabolic diseases before they contribute to additional morbidity. OBJECTIVES: To identify high- and low-risk dog breeds for CaOx uroliths and to determine the relationship of age and sex to the development of CaOx uroliths. ANIMALS: Calcium oxalate urolith submissions between 2010 and 2015. METHODS: A comparative cross-sectional study was conducted to identify high- and low-risk breeds for CaOx uroliths by comparing cases to multiple comparison groups. At-risk breeds were identified if odds ratios were significant (P value <.05) across all comparison groups. RESULTS: Of 258 898 urolith submissions, 124 285 were CaOx. Calcium oxalate was identified in 212 breeds. Twelve breeds were identified as high-risk breeds, and 14 breeds were identified as low-risk breeds. All high-risk breeds were small dog breeds, and all low-risk breeds were medium to large dog breeds. Overall, the mean age ± standard deviation of the first CaOx urolith was 8.4 ± 2.8 years. CONCLUSIONS AND CLINICAL IMPORTANCE: To achieve the health benefits of preclinical evaluation, breeds at high risk for CaOx urolithiasis should be screened at 5 to 6 years of age, which is 2 to 3 years before likely development of clinical urolithiasis.


Assuntos
Doenças do Cão/epidemiologia , Nefrolitíase/veterinária , Cálculos Urinários/veterinária , Fatores Etários , Animais , Oxalato de Cálcio/análise , Estudos Transversais , Doenças do Cão/genética , Cães , Feminino , Predisposição Genética para Doença , Masculino , Nefrolitíase/epidemiologia , Nefrolitíase/genética , Fatores de Risco , Fatores Sexuais , Estados Unidos , Cálculos Urinários/química , Cálculos Urinários/epidemiologia
19.
Circ Cardiovasc Imaging ; 12(6): e009228, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31195818

RESUMO

Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25. Results At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (ß=1.218; adjusted P=0.007), higher LV end-diastolic volume (ß=0.811; adjusted P=0.007), higher LV end-systolic volume (ß=0.350; adjusted P=0.048), higher left atrial volume (ß=0.214; adjusted P=0.009), and higher E/e' ratio (ß=0.059; adjusted P=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (ß=4.789; adjusted P<0.001), but not in whites (ß=1.051; adjusted P=0.283). Conclusions Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/complicações , Calcificação Vascular/diagnóstico por imagem , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Fatores Etários , Vasos Coronários/diagnóstico por imagem , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
Diabetologia ; 62(8): 1366-1374, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31115643

RESUMO

AIMS/HYPOTHESIS: The aim of this study was to determine whether long-term intra-individual variability in fasting glucose (FG) during young adulthood is associated with incident diabetes, cardiovascular disease (CVD) and mortality. METHODS: We included participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 18-30 years at baseline (1985-1986) and followed with eight examinations for up to 30 years. Long-term glucose variability was assessed using the CV (CV-FG) and the absolute difference between successive FG measurements (average real variability; ARV-FG). For participants who developed any event (diabetes, CVD or mortality), FG variability measurement was censored at the examination prior to event ascertainment. We estimated HRs for incident diabetes, CVD and mortality with adjustment for demographics, baseline FG, change in FG (censor - baseline) and time-varying education, smoking, alcohol consumption, BMI, physical activity, systolic BP, BP medications, LDL-cholesterol and cholesterol medications (and incident diabetes and diabetes medications for CVD and mortality outcomes). RESULTS: Among 3769 black and white participants, there were 317 incident diabetes cases (102,677 person-years), 159 incident CVD events (110,314 person-years) and 174 deaths (111,390 person-years). After adjustment, HRs per 1 SD higher ARV-FG were 1.64 (95% CI 1.52, 1.78) for diabetes, 1.15 (95% CI 1.01, 1.31) for CVD and 1.25 (95% CI 1.11, 1.40) for mortality. The HRs per 1 SD higher CV-FG were 1.39 (95% CI 1.21, 1.58) for diabetes, 1.32 (95% CI 1.13, 1.54) for CVD and 1.08 (95% CI 0.92, 1.27) for mortality, after adjustment. The cause-specific HRs per 1 SD higher ARV-FG were 1.29 (95% CI 1.14, 1.47) for non-CVD death and 1.05 (95% CI 0.76, 1.45) for CVD death. We did not observe evidence for effect modification of any association by sex or race. CONCLUSIONS/INTERPRETATION: Our results suggest that higher intra-individual FG variability during young adulthood before the onset of diabetes is associated with incident diabetes, CVD and mortality.


Assuntos
Glicemia/análise , Doenças Cardiovasculares/sangue , Complicações do Diabetes/sangue , Diabetes Mellitus/sangue , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Diabetes Mellitus/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos , Adulto Jovem
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