Publications by authors named "David R Jacobs"

785 Publications

Cross-Sectional and Longitudinal Associations of Lifestyle Behaviors with Pericardial Adipose Tissue: The MESA Study.

Med Sci Sports Exerc 2022 Jun 25;54(6):984-993. Epub 2022 Jan 25.

Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.

Purpose: We examined associations of sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA) with pericardial adipose tissue (PAT).

Methods: Adults from the Multi-Ethnic Study of Atherosclerosis were included from exam years 1 (2000-2002; N = 6057; mean age, 62.2 yr; 52.9% female, 38.0% White; 12.8% Chinese American, 26.7% African American, 22.5% Hispanic American), 2 (2002-2004), and 3 (2004-2005). Weekly volume of SB, LPA, and MVPA (in MET-hours per week) was reported using a questionnaire. PAT volume (in cubic centimeters) was quantified using computed tomography, analysis of covariance, and repeated-measures linear mixed models with adjustment for covariates (sociodemographics, cardiovascular disease risk factors, inflammation, waist circumference) tested cross-sectional and longitudinal associations, respectively.

Results: In cross-sectional analysis, the highest tertile of SB (β = 2.71; 95% confidence interval (CI), 0.69 to 4.73; P < 0.01) and the middle tertile of MVPA (β = -1.97; 95% CI, -3.92 to -0.02; P < 0.05) were associated with PAT, whereas no association was observed for LPA in fully adjusted models. In longitudinal models, SB, LPA, and MVPA were not associated with PAT in the full study sample; however, LPA was inversely associated with PAT among Whites in stratified analysis (β = -0.54; 95% CI, -0.95 to -0.13; P < 0.05).

Conclusions: Lower SB and higher LPA (among Whites only) and MVPA may be associated with lower PAT, but additional longitudinal research is needed.
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http://dx.doi.org/10.1249/MSS.0000000000002866DOI Listing
June 2022

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

J Am Heart Assoc 2022 May 16;11(10):e023038. Epub 2022 May 16.

Division of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MN.

Background The enterosalivary nitrate-nitrite-nitric oxide (NO-NO-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO, NO, or ammonia [NH]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH summary ratio was inversely associated with a -0.10 (false discovery rate =0.003) lower composite cardiometabolic score in simple adjusted models. Higher NH summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate =0.04) higher composite cardiometabolic score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.
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http://dx.doi.org/10.1161/JAHA.121.023038DOI Listing
May 2022

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

Eur Heart J 2022 Apr 25. Epub 2022 Apr 25.

Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, Presbyterian Hospital 9th Floor, Suite 105, New York, NY 10032, USA.

Aims: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF).

Methods And Results: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking.

Conclusion: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.
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http://dx.doi.org/10.1093/eurheartj/ehac205DOI Listing
April 2022

Early microbial markers of periodontal and cardiometabolic diseases in ORIGINS.

NPJ Biofilms Microbiomes 2022 Apr 20;8(1):30. Epub 2022 Apr 20.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.
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http://dx.doi.org/10.1038/s41522-022-00289-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021254PMC
April 2022

Respiratory Symptom Screening in Prevention.

Chest 2022 Apr;161(4):876-877

University of Minnesota School of Public Health, Division of Epidemiology and Community Health, Minneapolis, MN.

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http://dx.doi.org/10.1016/j.chest.2021.11.019DOI Listing
April 2022

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

N Engl J Med 2022 May 4;386(20):1877-1888. Epub 2022 Apr 4.

From the Division of Epidemiology and Community Health, School of Public Health (D.R.J.), and the Department of Pediatrics, University of Minnesota Medical School (A.R.S., J.S.), University of Minnesota, Minneapolis; the Division of Biostatistics and Epidemiology (J.G.W., N.Z.), and the Heart Institute (E.M.U.), Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine (J.G.W., N.Z., E.M.U.) - both in Cincinnati; the Department of Pediatrics, University of Colorado School of Medicine, and Anschutz Medical Campus, Children's Hospital Colorado - both in Aurora (S.R.D.); the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Research Center of Applied and Preventive Cardiovascular Medicine (J.I., N.K., C.G.M., O.T.R.), and the Departments of Medicine (M.J., J.S.A.V.) and Mathematics and Statistics (N.K.), University of Turku, and the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Division of Medicine (M.J., J.S.A.V.), and the Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Turku, and the Department of Clinical Chemistry, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, and the Faculty of Medicine and Health Technology, Tampere University, Tampere (T.L.) - all in Finland; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS (C.G.M., A.J.V., T.D.), and the Heart Research Group, Murdoch Children's Research Institute, Melbourne, VIC (T.D.) - both in Australia; the School of Public Health and Tropical Medicine, Tulane University, New Orleans (L.A.B.); the Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (T.L.B.); the Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (R.J.P.); and the Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom (T.D.).

Background: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.

Methods: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.

Results: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.

Conclusions: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).
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http://dx.doi.org/10.1056/NEJMoa2109191DOI Listing
May 2022

Unraveling disease pathways involving the gut microbiota: the need for deep phenotyping and longitudinal data.

Am J Clin Nutr 2022 May;115(5):1261-1262

Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1093/ajcn/nqac052DOI Listing
May 2022

Cardiorespiratory Fitness in Adults Aged 18 to 34 Years and Long-Term Pericardial Adipose Tissue (from the Coronary Artery Risk Development in Young Adults Study).

Am J Cardiol 2022 Jun 20;172:130-136. Epub 2022 Mar 20.

Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, Iowa; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.

Pericardial adipose tissue (PAT), an ectopic adipose depot surrounding the coronary arteries, is a pathogenic risk marker for cardiometabolic disease; however, the association between cardiorespiratory fitness (CRF) and PAT is unclear. Young adults (n = 2,614, mean age 25.1 years, 55.8% women, and 43.8% Black at baseline [1985 to 1986]) from the Coronary Artery Risk Development in Young Adults study were included. Maximal CRF was estimated at baseline, examination year 7 (1992 to 1993) and year 20 (2005 to 2006), using a symptom-limited maximal treadmill exercise test (duration in minutes) among those achieving ≥85% of age-predicted maximal heart rate. PAT volume (ml) was quantified at examination year 15 (2000 to 2001) and year 25 (2010 to 2011) using computed tomography. Multivariable linear and linear mixed regressions with covariates (sociodemographics, cardiovascular disease risk factors, inflammation, waist circumference) from baseline, year 7, and/or year 20 were used. Separate multivariable regression models revealed inverse associations of CRF at baseline, year 7, or year 20 with PAT at year 25 in fully adjusted models (all p <0.001). The linear mixed model showed that a 1-minute increase in treadmill exercise test duration over 20 years was associated with 1.49 ml lower subsequent PAT volume (p <0.001). In conclusion, findings suggest that higher CRF is inversely associated with subsequent PAT volume. Strategies to optimize CRF may be preventive against excessive PAT accumulation with age.
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http://dx.doi.org/10.1016/j.amjcard.2022.02.031DOI Listing
June 2022

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

J Hum Hypertens 2022 Mar 16. Epub 2022 Mar 16.

Department of Family Medicine, University of California San Diego, La Jolla, CA, USA.

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.
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http://dx.doi.org/10.1038/s41371-022-00669-xDOI Listing
March 2022

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

Am J Epidemiol 2022 Mar 12. Epub 2022 Mar 12.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established United States (US) prospective cohort studies. Starting as early as 1971, C4R cohorts have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health.
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http://dx.doi.org/10.1093/aje/kwac032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992336PMC
March 2022

Gestational Diabetes Mellitus Is Associated with Differences in Human Milk Hormone and Cytokine Concentrations in a Fully Breastfeeding United States Cohort.

Nutrients 2022 Feb 4;14(3). Epub 2022 Feb 4.

Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA.

It is unclear whether gestational diabetes mellitus (GDM) alters breast milk composition. We prospectively examined associations of GDM status with concentrations of six potentially bioactive elements (glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), leptin, and adiponectin) in human milk. These were measured at both 1 and 3 months postpartum in 189 fully breastfeeding women. Mixed-effects linear regression assessed GDM status-related differences in these milk bioactives, adjusting for demographics, maternal factors, and diet. At 1 and 3 months postpartum, milk CRP was higher (1.46 ± 0.31 ng/mL; < 0.001 and 1.69 ± 0.31 ng/mL; < 0.001) in women with GDM than in women without GDM, whereas milk glucose (-5.23 ± 2.22 mg/dL; = 0.02 and -5.70 ± 2.22; = 0.01) and milk insulin (-0.38 ± 0.17 μIU/mL; = 0.03 and -0.53 ± 0.17; = 0.003) were lower in women with GDM. These significant associations remained similar after additional adjustment for maternal weight status and its changes. No difference was found for milk IL-6, leptin, and adiponectin. There was no evidence of association between these milk bioactive compounds and 1 h non-fasting oral glucose challenge serum glucose in the women without GDM. This prospective study provides evidence that potentially bioactive elements of human milk composition are altered in women with GDM.
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http://dx.doi.org/10.3390/nu14030667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838140PMC
February 2022

Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.

Nutrients 2022 Jan 21;14(3). Epub 2022 Jan 21.

Division of Epidemiology and Community Health, University of Minnesota-Twin Cities, Minneapolis, MN 55454, USA.

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18-30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55-0.96) for CHD and 0.70 (0.50-0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.
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http://dx.doi.org/10.3390/nu14030469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837984PMC
January 2022

Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife.

JAMA Netw Open 2022 03 1;5(3):e221175. Epub 2022 Mar 1.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Baltimore, Maryland.

Importance: Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk.

Objective: To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife.

Design, Setting, And Participants: This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020.

Exposures: Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use.

Main Outcomes And Measures: Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy.

Results: Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; 95% CI, 0.23 to 0.82; elevated: β, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow.

Conclusions And Relevance: Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.1175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914577PMC
March 2022

Dietary Patterns and Prevalent NAFLD at Year 25 from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Nutrients 2022 Feb 18;14(4). Epub 2022 Feb 18.

Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

The prevalence of nonalcoholic fatty liver disease is rapidly rising. We aimed to investigate associations of diet quality and dietary patterns with nonalcoholic fatty liver disease (NAFLD) in Black and White adults. We included 1726 participants who attended the Year 20 Exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study and had their liver attenuation (LA) measured using computed tomography at Year 25 (2010-2011). NAFLD was defined as an LA of ≤51 Hounsfield units after the exclusion of other causes of liver fat. The a priori diet-quality score (APDQS) was used to assess diet quality, and dietary patterns were derived from principal components analysis. Univariate and multivariable logistic regression models were used to evaluate the association between the APDQS, dietary patterns, and NAFLD, and were adjusted for Year 20 covariates. NAFLD prevalence at Year 25 was 23.6%. In a model adjusted for age, race, sex, education, alcohol use, physical activity, smoking, and center at Year 25, the APDQS was inversely associated ( = 0.004) and meat dietary pattern was positively associated ( < 0.0001) with NAFLD, while the fruit-vegetable dietary pattern was not significantly associated ( = 0.40). These associations remained significant when additionally adjusting for comorbidities (type 2 diabetes mellitus, dyslipidemia, hypertension), however, significant associations were diminished after additionally adjusting for body mass index (BMI). Overall, this study finds that the APDQS and meat dietary patterns are associated with prevalent NAFLD in mid-life. The associations appear to be partially mediated through higher BMI.
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http://dx.doi.org/10.3390/nu14040854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878386PMC
February 2022

Pooled Cohort Probability Score for Subclinical Airflow Obstruction.

Ann Am Thorac Soc 2022 Feb 17. Epub 2022 Feb 17.

Columbia University, Medicine, New York, New York, United States.

Rationale: Early detection of COPD is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening.

Objective: To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs.

Methods: Lung function and clinical data were harmonized and pooled across 9 US general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (FEV1/FVC<0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES 2011-12). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in 4 of 9 cohorts.

Results: Of 33,546 participants (mean age 52 years, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk=14,024) was 3-fold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race/ethnicity, BMI, smoking status, smoking pack-years) was well-calibrated and showed excellent discrimination in both the testing sample (C-statistic 0.81, 95%CI 0.80-0.82) and in NHANES (C-statistic 0.83, 95%CI 0.80-0.86). Among participants with predicted probabilities ≥15%, 3.2 would need to undergo spirometry in order to detect one case of SAO.

Conclusions: Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.
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http://dx.doi.org/10.1513/AnnalsATS.202109-1020OCDOI Listing
February 2022

PDAY risk score predicts cardiovascular events in young adults: the CARDIA study.

Eur Heart J 2022 Feb 9. Epub 2022 Feb 9.

Department of Preventive Medicine, Feinberg Medical School, Northwestern University, Chicago, IL, USA.

Aims: Atherosclerotic cardiovascular disease (ASCVD) risk prediction equations apply to older adults. For this study, the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) risk score, based on post-mortem measurements of atherosclerosis in 15-34-year olds dying accidentally, was used to predict ASCVD events, specifically myocardial infarction and revascularization, in middle age, from risk measured at ≤40 years of age.

Methods And Results: The Coronary Artery Risk Development in Young Adults Study (CARDIA) collected longitudinal cardiovascular risk data, coronary artery calcium (CAC) scores, and ASCVD data beginning at age 18 and 30 years with 30-year follow-up. Predictive accuracy for ASCVD of the PDAY risk score, calculated at baseline (mean age 24) and at all six CARDIA examinations up until year 15, was examined. We also examined whether the presence of CAC improved model discrimination. The cohort for this study comprised 5004 Black and White men and women, at baseline and 3558 with data at year 15. Each standard deviation increase in PDAY score, at each examination, was significantly associated with future ASCVD. Hazard ratios (per standard deviation) increased from 1.74 to 2.04 from year 0 to year 15. C-statistics ranged from 0.771 to 0.794. Coronary artery calcium measurement at age 33-45 years improved risk prediction only if the score was 0. Cumulative risk exposure over the first 15 years of the CARDIA study also had high-predictive value (c-statistic 0.798, 95% confidence interval 0.762-0.835).

Conclusion: The PDAY risk score may be used in young adults, prior to age 40 years to predict ASCVD events.

Key Question: Can risk for coronary artery disease be predicted by the PDAY risk score, derived from autopsied adolescents and young adults using atherosclerosis measures and post-mortem risk factors?

Key Finding: The PDAY risk score was highly predictive of incident coronary artery disease occurring in young adulthood, beginning at 18-30 years of age. Coronary artery calcium (CAC) measurement obtained at age 33-45 years added to prediction only if zero.

Take-home Message: Risk factors for atherosclerosis as measured in the PDAY study are highly predictive of coronary artery disease events in young adults.
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http://dx.doi.org/10.1093/eurheartj/ehac009DOI Listing
February 2022

Pulmonary Function in Midlife as a Predictor of Later-Life Cognition: The Coronary Artery Risk Development in Adults (CARDIA) Study.

J Gerontol A Biol Sci Med Sci 2022 Feb 1. Epub 2022 Feb 1.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: Studies found associations between pulmonary function (PF) and cognition, but these are limited by mostly cross-sectional design and a single measure of PF (typically FEV1). Our objective was to prospectively analyze the association of repeatedly measured PF with cognition.

Methods: We studied 3,499 participants in The Coronary Artery Risk Development in Young Adults cohort with cognition measured at year 25 (Y25) and Y30, and PF (FEV1 and FVC, reflecting better PF) measured up to six times from Y0-Y20. Cognition was measured via Stroop test, Rey-Auditory Verbal Learning Test [RAVLT], and Digit Symbol Substitution Test [DSST] which capture executive function, verbal learning and memory, and attention and psychomotor speed respectively; lower Stroop, and higher RAVLT and DSST scores indicate better cognition. We modeled linear, cross-sectional associations between cognition and PF at Y30 (mean age 55), and mixed models to examine associations between cognition at Y25-Y30 and longitudinal PF (both annual rate of change, and cumulative PF from Y0-Y20).

Results: At Y30 FEV1 and FVC were cross-sectionally associated with all three measures of cognition (β= 0.08-0.12, p<0.01-0.02). Annual change from peak FEV1/FVC ratio was associated with Stroop and DSST (β=18.06, 95% CI=7.71-28.40; β=10.30, 95% CI=0.26-20.34, respectively) but not RAVLT. Cumulative FEV1 and FVC were associated with Stroop and DSST (β= 0.07-0.12, p<0.01-0.02), but only cumulative FEV1 was associated with RAVLT (β=0.07, 95% CI=0.00-0.14).

Conclusions: We identified prospective associations between measures of PF and cognition even at middle ages, adding evidence of a prospective association between reduced PF and cognitive decline.
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http://dx.doi.org/10.1093/gerona/glac026DOI Listing
February 2022

Plasma lipid profiles in early adulthood are associated with epigenetic aging in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Clin Epigenetics 2022 01 31;14(1):16. Epub 2022 Jan 31.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA.

Background: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with atherosclerotic cardiovascular disease. However, the associations between early adulthood lipid levels and GAA in midlife are unknown. Also, it is unknown whether GAA mediates the associations between lipid levels in young adults and subclinical atherosclerosis in midlife.

Results: We estimated measures of epigenetic age acceleration in 1118 White and Black participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at examination years (Y) 15 and 20. We used multivariable regression models to examine associations of Y15 and Y20 GAA estimates with plasma lipid levels measured at prior examination years (Y0, Y5, and Y10) and concurrently: triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. Mediation analysis was used to assess the extent to which GAA may mediate associations between plasma lipids and coronary artery calcification (CAC). In our study each 1-SD higher cumulative TG level was associated with an average 0.73 ± 0.12 years older GAA. Each 1-SD higher cumulative HDL-C level was associated with an average 0.57 ± 0.17 years younger GAA. Stratified analyses showed that the associations between TG and GAA were stronger among female and Black participants and the associations between HDL-C and GAA were stronger among female and White participants. GAA statistically mediated 17.4% of the association of cumulative TG with CAC.

Conclusions: High TG and low HDL-C in early adulthood are associated with accelerated epigenetic aging by midlife. Increased epigenetic age acceleration may partially mediate the associations between high TG levels and the presence of subclinical atherosclerosis.
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http://dx.doi.org/10.1186/s13148-021-01222-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805309PMC
January 2022

Monocyte miRNAs Are Associated With Type 2 Diabetes.

Diabetes 2022 04;71(4):853-861

Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC.

miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222-3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p), our findings suggest a dose-response relationship with impaired fasting glucose and T2D. Two of the six miRNAs were associated with incident T2D (miR-92b-3p: hazard ratio [HR] 1.64, P = 1.30E-03; miR-222-3p: HR 1.97, P = 9.10E-03) in the highest versus lowest tertile of expression. Most of the T2D-associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic network. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.
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http://dx.doi.org/10.2337/db21-0704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965663PMC
April 2022

Weight gain trajectories and obesity rates in intensive and conventional treatments of type 1 diabetes from the DCCT compared with a control population without diabetes.

Diabet Med 2022 05 26;39(5):e14794. Epub 2022 Jan 26.

Knight Cardiovascular Institute and Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

Aim: Obesity is a significant health issue for participants with type 1 diabetes undergoing intensive diabetes management. The temporal pattern and factors associated with weight gain after treatment initiation remain poorly understood including how weight gain in participants with and without type I diabetes compare. Our aim was to compare weight gain in those receiving intensive (INT) and conventional (CONV) type 1 diabetes treatment to a population without diabetes.

Methods: Participants included men and women of 18 years and older in the Diabetes Control and Complications Trial (DCCT) randomized to INT (n = 562) or CONV (n = 568) and a prospective, observational cohort without diabetes from the Coronary Artery Development in Young Adults (CARDIA, controls) study (n = 2446). Body mass index (BMI) trajectories and obesity prevalence were compared between groups and candidate metabolic and therapeutic moderators investigated.

Results: Annual weight gain with INT peaked 1.3 years after initiation and was greater than both CONV and controls before and after this peak. Obesity prevalence with INT was lower than controls at baseline, was similar to controls at 2 years and surpassed controls by 5 years. Obesity rates with CONV remained below controls at all time points. Greater annual weight gain in the DCCT was associated with lower haemoglobin A , higher insulin dose and family history of type 2 diabetes.

Conclusions: Greater weight gain accompanying INT therapy occurs in two stages, leads to similar or greater obesity rates than controls after 2 years and is primarily modified by glucose control and family history, supportive of a therapeutic-genetic influence on weight trajectories.
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http://dx.doi.org/10.1111/dme.14794DOI Listing
May 2022

Association Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.

JAMA 2021 12;326(22):2287-2298

Columbia University, New York, New York.

Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood.

Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults.

Design, Setting, And Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65 251 participants aged 18 to 102 years of whom 53 701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018).

Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1 less than 80% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1 greater than or equal to 80% predicted.

Main Outcomes And Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities.

Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4% women, 48.5% never-smokers), 4582 (8.5%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3% vs 31.4%; prevalence ratio [PR], 1.68 [95% CI, 1.55-1.82]), underweight (prevalence, 1.4% vs 1.0%; PR, 2.20 [95% CI, 1.72-2.82]), female sex (prevalence, 60.3% vs 59.0%; PR, 1.07 [95% CI, 1.01-1.13]), and current smoking (prevalence, 25.2% vs 17.5%; PR, 1.33 [95% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95% CI, 0.7-1.6]; adjusted HR, 1.95 [95% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95% CI, 2.1-3.4]; adjusted HR, 1.55 [95% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95% CI, 4.9-7.5]; adjusted HR, 1.90 [95% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95% CI, 3.7-5.8]; adjusted HR, 1.30 [95% CI, 1.18-1.42]).

Conclusions And Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal.
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http://dx.doi.org/10.1001/jama.2021.20939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672237PMC
December 2021

Association of Abdominal Aorta Calcium and Coronary Artery Calcium with Incident Cardiovascular and Coronary Heart Disease Events in Black and White Middle-Aged People: The Coronary Artery Risk Development in Young Adults Study.

J Am Heart Assoc 2021 12 7;10(24):e023037. Epub 2021 Dec 7.

Division of Cardiology Department of Medicine University of Minnesota Minneapolis MN.

Background Assessing coronary artery calcium (CAC) is among AHA/ACC prevention guidelines for people at least 40 years old at intermediate risk for coronary heart disease (CHD). To study enhanced risk stratification, we investigated the predictive value of abdominal aorta calcium (AAC) relative to CAC for cardiovascular disease (CVD) and CHD events in Black and White early middle-aged participants, initially free of overt CVD. Methods and Results In the CARDIA (Coronary Artery Risk Development in Young Adults) study, a multi-center, community-based, longitudinal cohort study of CVD risk, the CAC and AAC scores were assessed in 3011 participants in 2010-2011 with follow-up until 2019 for incident CVD and CHD events. Distributions and predictions, overall and by race, were computed. During the 8-year follow-up, 106 incident CVD events (55 were CHD) occurred. AAC scores tended to be much higher than CAC scores. AAC scores were higher in Black women than in White women. CAC predicted CVD with HR 1.77 (1.52-2.06) and similarly for AAC, while only CAC predicted CHD. After adjustment for risk factors and calcium in the other arterial bed, the association of CAC with CVD was independent of risk factors and AAC, while the association of AAC with CVD was greatly attenuated. However, AAC predicted incident CVD when CAC was 0. Prediction did not vary by race. Conclusions AAC predicted CVD nearly as strongly as CAC and could be especially useful as a diagnostic tool when it is an incidental finding or when no CAC is found.
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http://dx.doi.org/10.1161/JAHA.121.023037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075251PMC
December 2021

Gene expression of oxidative stress markers and lung function: A CARDIA lung study.

Mol Genet Genomic Med 2021 12 19;9(12):e1832. Epub 2021 Nov 19.

Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.

Background: Circulating markers of oxidative stress have been associated with lower lung function. Our objective was to study the association of gene expression levels of oxidative stress pathway genes (ALOX12, ALOX15, ARG2, GSTT1, LPO, MPO, NDUFB3, PLA2G7, and SOD3) and lung function forced expiratory volume in one second (FEV ), forced vital capacity (FVC) in Coronary Artery Risk Development in Young Adults study.

Methods: Lung function was measured using spirometry and the Nanostring platform was used to estimate gene expression levels. Linear regression models were used to study association of lung function measured at year 30, 10-year decline in lung function and gene expression after adjustment for center, smoking, and BMI, measured at year 25.

Results: The 10-year decline of FEV was faster in highest NDUFB3 quartile compared to the lowest (difference = -2.09%; p = 0.001) after adjustment for multiple comparisons. The 10-year decline in FEV and FVC was nominally slower in highest versus lowest quartile of PLA2G7 (difference = 1.14%; p = 0.02, and difference = 1.06%; p = 0.005, respectively). The other genes in the study were not associated with FEV or FVC.

Conclusion: Higher gene expression levels in oxidative stress pathway genes are associated with faster 10-year FEV decline.
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http://dx.doi.org/10.1002/mgg3.1832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683624PMC
December 2021

Characteristics associated with early- vs. later-onset adult diabetes: The CARDIA study.

Diabetes Res Clin Pract 2021 Dec 11;182:109144. Epub 2021 Nov 11.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, USA; Byrdine F. Lewis School of Nursing and Health Professions, Georgia State University, Atlanta, USA.

Aims: Differences in risk profiles for individuals with early- (<40 years old) vs. later-onset (≥40 years old) diabetes were examined.

Methods: A nested case-comparison study design using 30-year longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study was used. Survey data (socio-demographics, family history, medical records, and lifestyle behaviors), obesity-related measures (body mass index, weight), blood pressure, and laboratory data (insulin, fasting glucose, 2-h glucose, and lipids) were used to examine progression patterns of diabetes development in those with early-onset vs. later-onset diabetes.

Results: Of 605 participants, 120 were in early-onset group while 485 were in later-onset group. Early-onset group had a lower A Priori Diet Quality Score, but not statistically significant at baseline; however, the between-group difference became significant at the time that diabetes was first detected (p = 0.026). The physical activity intensity score consistently decreased from baseline to the development of diabetes in both the early- and later-onset groups. Early-onset group showed more dyslipidemia at baseline and at the time that diabetes was first detected, and rapid weight gain from baseline to the development of diabetes.

Conclusions: Emphases on lifestyle modification and risk-based diabetes screening in asymptomatic young adults are necessary for early detection and prevention.
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http://dx.doi.org/10.1016/j.diabres.2021.109144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688278PMC
December 2021

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

Int J Obes (Lond) 2022 02 2;46(2):393-399. Epub 2021 Nov 2.

Oxford Martin School, Oxford University, Oxford, UK.

Background: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce.

Methods: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries.

Results: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63).

Conclusions: Higher childhood BMI was independently associated with increased overall cancer mortality.
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http://dx.doi.org/10.1038/s41366-021-01000-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794778PMC
February 2022

Prevalence Implications of the 2017 American Academy of Pediatrics Hypertension Guideline and Associations with Adult Hypertension.

J Pediatr 2022 02 5;241:22-28.e4. Epub 2021 Oct 5.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH; University of Cincinnati College of Medicine, Cincinnati, OH.

Objective: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline ("Fourth Report"), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium.

Study Design: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated.

Results: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG.

Conclusions: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension.
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http://dx.doi.org/10.1016/j.jpeds.2021.09.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924915PMC
February 2022

Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events.

JAMA Cardiol 2021 12;6(12):1406-1413

Division of General Medicine, Columbia University Medical Center, New York, New York.

Importance: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk.

Objective: To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life.

Design, Setting, And Participants: This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021.

Exposures: Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years.

Main Outcomes And Measures: Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF).

Results: A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF.

Conclusions And Relevance: This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.
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http://dx.doi.org/10.1001/jamacardio.2021.3508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459309PMC
December 2021

Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study.

Am J Med 2022 02 9;135(2):211-218.e1. Epub 2021 Sep 9.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Purpose: There are limited data on the relationship between neighborhood level factors and their association with lung health independent of individual socioeconomic status. We sought to determine whether baseline neighborhood level socioeconomic deprivation in young adults is associated with greater 20-year decline in lung function and higher risk of future lung disease, independent of baseline individual income, education, and smoking status.

Methods: This multicenter population-based cohort study included 2689 participants in Coronary Artery Risk Development in Young Adults (CARDIA) for whom neighborhood deprivation was determined at year 10 (baseline for study) and who had complete lung function measurements at years 10 and 30. Baseline neighborhood deprivation was defined using 1990 Census blocks as a combination of 4 factors involving median household income, poverty level, and educational achievement. The outcomes were decline in lung function over 20 years (year 10 to 30) and odds of emphysema (year 25).

Results: In multivariable regression models, greater baseline neighborhood deprivation was associated with greater decline in lung function (-2.34 mL/year excess annual decline in forced expiratory volume in 1 second (FEV) in the highest versus lowest deprivation quartile (P = .014)). Furthermore, baseline neighborhood deprivation was independently associated with greater odds of emphysema (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.42-6.30).

Conclusions: Residence in neighborhoods with greater socioeconomic deprivation in young adulthood, independent of individual income and smoking, is associated with greater 20-year decline in forced expiratory volume in 1 second and higher risk of future emphysema.
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http://dx.doi.org/10.1016/j.amjmed.2021.07.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840953PMC
February 2022

Long-term television viewing patterns and gray matter brain volume in midlife.

Brain Imaging Behav 2022 Apr 6;16(2):637-644. Epub 2021 Sep 6.

San Francisco VA Health Care System, San Francisco, CA, USA.

The purpose of this study was to investigate whether long-term television viewing patterns, a common sedentary behavior, in early to mid-adulthood is associated with gray matter brain volume in midlife and if this is independent of physical activity. We evaluated 599 participants (51% female, 44% black, mean age 30.3 ± 3.5 at baseline and 50.2 ± 3.5 years at follow-up and MRI) from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study. We assessed television patterns with repeated interviewer-administered questionnaire spanning 20 years. Structural MRI (3T) measures of frontal cortex, entorhinal cortex, hippocampal, and total gray matter volumes were assessed at midlife. Over the 20 years, participants reported viewing an average of 2.5 ± 1.7 h of television per day (range: 0-10 h). After multivariable adjustment, greater television viewing was negatively associated with gray matter volume in the frontal (β = - 0.77; p = 0.01) and entorhinal cortex (β = - 23.83; p = 0.05) as well as total gray matter (β = - 2.09; p = 0.003) but not hippocampus. These results remained unchanged after additional adjustment for physical activity. For each one standard deviation increase in television viewing, the difference in gray matter volume z-score was approximately 0.06 less for each of the three regions (p < 0.05). Among middle-aged adults, greater television viewing in early to mid-adulthood was associated with lower gray matter volume. Sedentariness or other facets of television viewing may be important for brain aging even in middle age.
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http://dx.doi.org/10.1007/s11682-021-00534-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898315PMC
April 2022
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