Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long‐term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001–2002) and underwent ultrasound imaging at follow‐up (2013–2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10‐year atherosclerotic cardiovascular disease risk <7.5%, there were 162 people (32%) who developed premature atherosclerosis. Aside from younger age (risk ratio [RR], 1.21; 95% CI, 1.07–1.36, per 10 years) and a total cholesterol/high‐density lipoprotein cholesterol ratio <3.5 (RR, 1.15; 95% CI, 1.01–1.30), normal values of traditional risk factors did not predict long‐term absence of plaque. Independent from traditional markers including glomerular filtration rate, serum calcium‐phosphate product (RR, 1.07; 95% CI, 1.01–1.14, per 1‐SD lower), phosphate (RR, 1.15; 95% CI, 1.03–1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR, 1.20; 95% CI, 1.02–1.41) were significantly associated with the non‐development of plaque. Conclusions Nearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium‐phosphate homeostasis and low sodium intake were associated with long‐term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.
Export Background and objectives Previous studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD. Design, setting, participants, & measurements The Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression. Results Over a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality. Conclusions Hard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.
Background: Persons with obesity are at high risk of obstructive sleep apnea (OSA); however, the relationship between obesity in young adulthood and future OSA risk is unknown. Methods: We prospectively examined the association between changes in measures of adiposity in young adulthood and subsequent risk of OSA in 857 middle-aged adults free of cardiovascular disease at baseline. Data included at least 2 measures of adiposity (BMI, waist circumference, waist/hip ratio, and waist/height ratio) after 18 years of age. High-risk of OSA was defined as 2 of the following: hypertension, persistent snoring, and persistent daytime sleepiness, based on modified Berlin Questionnaire score, excluding BMI. Persistent snoring was defined as snoring on ≥3 nights/week, snoring louder than talking or very loud, and breathing pauses on ≥3 nights/week. Persistent daytime sleepiness was defined as feeling tired ≥3 days/week after sleeping, feeling tired during time awake ≥3 days/week, and falling asleep while driving. Results: The sample was 42% male and 32% African-American. Mean age was 43 years and mean BMI was 31 kg/m 2 when sleep outcomes were measured. BMI increased by 6.1 kg/m 2 over 25 years, waist circumference increased by 16.4 cm over 22 years, waist/hip ratio increased by 0.05 over 15 years, and waist/height ratio increased by 0.09 over 22 years. There were 235 (27%) participants with high-risk of OSA. In multivariate log linear regression models, participants with a one standard deviation increase in BMI had 1.30 (95% CI: 1.14, 1.49) times the risk of OSA, after adjustment for age, gender, race, educational level, leisure-time physical activity, regular drinking, current smoking, and years of follow-up. Participants with a one standard deviation increase in BMI, waist circumference, and waist/height ratio had 1.35 (95% CI: 1.22, 1.50), 1.17 (95% CI: 1.08, 1.27), and 1.22 (95% CI: 1.11, 1.34) times the risk of persistent snoring. The association was not significant for persistent daytime sleepiness. Waist/hip ratio was not significantly associated with any sleep-related outcome. Conclusions: Our findings suggest that an increase in BMI in young adulthood is an independent predictor of high-risk of OSA in middle age. Increases in BMI, waist circumference, and waist/height ratio are independently associated with persistent snoring in middle age.
Background: The coronary artery calcium (CAC) score is associated with the risk of coronary heart disease. We aimed to assess the relationship between low-carbohydrate dietary patterns and CAC scores in the MESA cohort. Methods: Our sample included 5,702 men and women who were free of clinical cardiovascular disease and had food frequency questionnaires at baseline (2000-2002), and at least one measure of CAC during follow-up. We excluded those with implausible energy intake (<600 kcal/day or >6000 kcal/day) or daily physical activity (>24 hours). Two low-carbohydrate-diet (LCD) scores were generated: an overall LCD score was calculated based on total carbohydrate, fat, and protein, and a plant-based LCD score was calculated using intakes of unsaturated fat (excluding trans fat) and vegetable protein. CAC scores at exam 1 and at 2 and 3 (18 and 36 months later) were used in multivariable relative risk regression models to examine the association between LCD scores and CAC prevalence and incidence (binary), while robust regression was used to examine CAC progression (continuous). Analyses were adjusted for demographic, socioeconomic, lifestyle, and cardiovascular risk factors. Results: The mean age was 62 years, 48% of participants were male, and 40.8% were White. The mean (SD) levels of carbohydrate intake as a percentage of energy were 64.2 (5.2), 56.1 (4.9), 51.5 (3.7), 47.5 (4.0), and 42.1 (5.6) from the lowest to the highest quintiles of the overall LCD score. There were 2,652 (46.5%) participants who had positive CAC scores at baseline and 252 participants who had newly positive scores for CAC during follow-up. Among those with prevalent CAC at baseline, the median (IQR) of increases in CAC was 47 (132) over follow-ups. For incident CAC, relative risk estimates (95% CI) from Quintile 1 to 5 were 1, 0.73 (0.52, 1.02), 0.65 (0.45, 0.95), 0.90 (0.63, 1.28), 1.05 (0.77, 1.42) for overall LCD scores, and were 1, 1.14 (0.81, 1.61), 0.98 (0.71, 1.37), 1.08 (0.78, 1.49), 1.15 (0.82, 1.62) for plant-based LCD scores, respectively. No significant trend was observed for associations with incident CAC. There was no significant association between any LCD score and CAC prevalence or progression among those with positive CAC scores at baseline. Conclusions: A low-carbohydrate diet, including a plant-based low-carbohydrate diet, was not associated with prevalence, incidence, or progression of CAC among those with prevalent CAC at baseline.
Chronic kidney disease (CKD) is an important public health challenge due to its high prevalence, potential for progression to end-stage renal disease, and associated increases in risks of cardiovascular disease morbidity and mortality. While traditional risk factors for reduced kidney function have been identified, the biological pathways underlying this complex phenotype remain largely unknown. A metabolome-wide association study was conducted among 825 white and 436 African-American participants of the Bogalusa Heart Study (BHS) to identify metabolites associated with kidney function. Estimated glomerular filtration rate (eGFR) was calculated among BHS participants using the CKD Epidemiology Collaboration (CKD-EPI) equation. Untargeted, ultra-high performance liquid chromatography tandem-mass spectroscopy was used to quantify 1,466 metabolites. A total of 1,202 metabolites passing rigorous quality control were tested for association with eGFR in race stratified and combined multiple regression analyses that adjusted for age, sex, education, cigarette smoking, alcohol drinking, physical activity, body mass index, and race (in combined analyses). Significant metabolites were identified as those achieving Bonferroni corrected significance (P<4.16х10 -5 ) in one race group and the entire cohort, with a similar trend observed in the other race group. Results of these analyses are presented in the Figure . Among 302 significant metabolites, 89 were novel and in known metabolic pathways, 106 were novel and in unknown metabolic pathways, and 107 were previously reported. The 89 novel metabolites were classified into the following pathways: 40 in amino acids, 3 in carbohydrates, 7 in cofactors, 1 in energy, 6 in nucleotides, 9 in peptides, and 14 in xenobiotics. In conclusion, the current analysis not only validated previous findings, but identified novel metabolites associated with kidney function. These data provide important insights into the biological pathways underlying this complex phenotype.
Research indicates that sleep duration and quality are inter-related factors that contribute to obesity, but few studies have focused on sleep chronotype, representing an individual's circadian proclivity, nor assessed these factors in racially diverse middle-aged samples. We examined the associations between chronotype and obesity among black and white men and women participating in the Bogalusa Heart Study (BHS).Body mass index (BMI) and sleep data were available for 1,197 middle-aged men and women (mean age 48.2 ± 5.3 years) who participated in the BHS 2013–2016. Based on the reduced Morningness-Eveningness Questionnaire's cutoff values for chronotypes, we combined 'definitely morning' and 'moderately morning' types into 'morning' type, 'definitely evening' and 'moderately evening' types into 'evening' type and kept those who were "neither" type in a separate group. We used 'morning' type as the referent group. Obesity was defined as a BMI ≥ 30. Multivariable logistic regression models were used to examine associations adjusting for sex, age, education, smoking, alcohol use and drug use, depression, shift work, physical activity and sleep duration.Evening chronotype, reported by 11.1% of participants, was associated with obesity after multi-variable adjustment, including shift work, physical activity and sleep duration (OR 1.67, 95% CI: 1.08–2.56). However, once stratified by race (black/white), this association was found only among white participants (OR = 1.91, 95% CI = 1.12–3.25) after full adjustment.In our biracial, community-based population, evening chronotype was independently associated with obesity, specifically among white participants. Further research is needed to identify behavioral, endocrine, nutritional and genetic pathways which underlie these associations.
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