Background Although sufficient and healthy sleep is inversely associated with cardiovascular disease (CVD) and its risk factors, the American Heart Association's Life's Simple 7 (LS7), as a measure ...of cardiovascular health (CVH), did not include sleep. We evaluated an expanded measure of CVH that includes sleep as an eighth metric in relation to CVD risk. Methods and Results The analytic sample consisted of MESA (Multi-Ethnic Study of Atherosclerosis) Sleep Study participants who had complete data on sleep characteristics from overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and the outcome. We computed the LS7 score and 4 iterations of a new CVH score: score 1 included sleep duration, score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea), scores 3 and 4 included sleep characteristics associated with CVD in MESA (score 3: sleep duration and efficiency, daytime sleepiness, and obstructive sleep apnea; score 4: score 3+sleep regularity). Multivariable-adjusted logistic and Cox proportional hazards models evaluated associations of the LS7 and CVH scores 1 to 4 with CVD prevalence and incidence. Among 1920 participants (mean age: 69±9 years; 54% female), there were 95 prevalent CVD events and 93 incident cases (mean follow-up, 4.4 years). Those in the highest versus lowest tertile of the LS7 score and CVH scores 1 to 4 had up to 80% lower odds of prevalent CVD. The LS7 score was not significantly associated with CVD incidence (hazard ratio, 0.62 95% CI, 0.37-1.04). Those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratio, 0.57 95% CI, 0.33-0.97; and hazard ratio, 0.53 95% CI, 0.32-0.89), respectively. Conclusions CVH scores that include sleep health predicted CVD risk in older US adults. The incorporation of sleep as a CVH metric, akin to other health behaviors, may enhance CVD primordial and primary prevention efforts. Findings warrant confirmation in larger cohorts over longer follow-up.
Summary
Irregular sleep and non‐optimal sleep duration separately have been shown to be associated with increased disease and mortality risk. We used data from the prospective cohort Multi‐Ethnic ...Study of Atherosclerosis sleep study (2010–2013) to investigate: do aging adults whose sleep is objectively high in regularity in timing and duration, and of sufficient duration tend to have increased survival compared with those whose sleep is lower in regularity and duration, in a diverse US sample? At baseline, sleep was measured by 7‐day wrist actigraphy, concurrent with at‐home polysomnography and questionnaires. Objective metrics of sleep regularity and duration from actigraphy were used for statistical clustering using sparse k‐means clustering. Two sleep patterns were identified: “regular‐optimal” (average duration: 7.0 ± 1.0 hr obtained regularly) and “irregular‐insufficient” (duration: 5.8 ± 1.4 hr obtained with twice the irregularity). Using proportional hazard models with multivariate adjustment, we estimated all‐cause mortality hazard ratios. Among 1759 participants followed for a median of 7.0 years (Q1–Q3, 6.4–7.4 years), 176 deaths were recorded. The “regular‐optimal” group had a 39% lower mortality hazard than did the “irregular‐insufficient” sleep group (hazard ratio 95% confidence interval: 0.61 0.45, 0.83) after adjusting for socio‐demographics, lifestyle, medical comorbidities and sleep disorders. In conclusion, a “regular‐optimal” sleep pattern was significantly associated with a lower hazard of all‐cause mortality. The regular‐optimal phenotype maps behaviourally to regular bed and wake times, suggesting sleep benefits of adherence to recommended healthy sleep practices, with further potential benefits for longevity.
Rest-activity rhythms (RARs), a measure of circadian rhythmicity in the free-living setting, are related to mortality risk, but evidence is limited on associations with cardiovascular disease (CVD) ...and its risk factors.
Participants included 4521 adults from the 2013 to 2014 National Health and Nutrition Examination Survey physical activity monitoring examination. Wrist-worn ActiGraph GT3X+ data were used to estimate RARs. Multivariable logistic models evaluated associations of RARs with prevalent CVD, hypertension, obesity, and central adiposity. Participants (mean age, 49 years) in the highest versus lowest tertile of relative amplitude (greater circadian rhythmicity) had 39% to 62% lower odds of prevalent CVD, hypertension, obesity, and central adiposity. A more active wake period was associated with 19% to 72% lower CVD, hypertension, obesity, and central adiposity odds. Higher interdaily stability (regular sleep-wake and rest-activity patterns) was related to 52% and 23% lower CVD and obesity odds, respectively. In contrast, participants in the highest versus lowest tertile of intradaily variability (fragmented RAR and inefficient sleep) had >3-fold and 24% higher CVD and obesity odds, respectively. A later and less restful sleep period was associated with 36% to 2-fold higher CVD, hypertension, obesity, and central adiposity odds. A statistically significant linear trend was observed for all associations (
-trend<0.05).
A robust, stable, and less fragmented RAR, an active wake period, and an earlier and more restful sleep period are associated with lower prevalent CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The magnitude, timing, and regularity of sleep-wake and rest-activity patterns may be important targets for reducing cardiovascular risk.
Abstract
Study Objectives:
Short sleep duration and poor sleep quality are associated with adverse cardiovascular outcomes. Potential pathophysiological mechanisms include sleep-associated ...alterations in the autonomic nervous system. The objective of this study was to examine the associations of shorter sleep duration and poorer sleep quality with markers of autonomic tone: heart rate (HR), high-frequency HR variability (HF-HRV) and salivary amylase.
Methods:
Cross-sectional analysis of data from actigraphy-based measures of sleep duration and efficiency and responses to a challenge protocol obtained from 527 adult participants in the Multi-Ethnic Study of Atherosclerosis.
Results:
Participants who slept fewer than 6 h per night (compared to those who slept 7 h or more per night) had higher baseline HR (fully adjusted model 0.05 log beats/min, 95% confidence interval CI 0.01, 0.09) and greater HR orthostatic reactivity (fully adjusted model 0.02 log beats/min, 95% CI 0.002, 0.023). Participants who slept 6 to less than 7 h/night (compared to those who slept 7 h or more per night) had lower baseline HF-HRV (fully adjusted model −0.31 log msec2, 95% CI −0.60, −0.14). Participants with low sleep efficiency had lower baseline HF-HRV than those with higher sleep efficiency (fully adjusted model −0.59 log msec2, 95% CI −1.03, −0.15). Participants with low sleep efficiency had higher baseline levels of amylase than those with higher sleep efficiency (fully adjusted model 0.45 log U/mL, 95% CI 0.04, 0.86).
Conclusions:
Short sleep duration, low sleep efficiency, and insomnia combined with short sleep duration were associated with markers of autonomic tone that indicate lower levels of cardiac parasympathetic (vagal) tone and/or higher levels of sympathetic tone.
Sleep duration and sleep quality are important predictors of risk for cardiovascular disease (CVD). One potential link between sleep health and CVD is through lifestyle factors such as diet. To ...clarify the association between diet and sleep, we assessed the associations of sleep duration and insomnia symptoms with current Mediterranean-style diet (aMed) and with historical changes in aMed score. Actigraphy-measured sleep duration and self-reported insomnia symptoms categorized as insomnia with short sleep (<6 hr/night), insomnia without short sleep, no insomnia with short sleep, and no insomnia or short sleep were obtained from 2068 individuals who also had dietary intake data. A 10-point aMed score, derived from a self-report food frequency questionnaire, was collected concurrently with the sleep assessment and 10 years before. Compared with individuals who currently reported a low aMed score, those with a moderate-high aMed score were more likely to sleep 6-7 vs. <6 hr/night (p < 0.01) and less likely to report insomnia symptoms occurring with short sleep (vs. no insomnia or short sleep alone; p < 0.05). An increase in aMed score over the preceding 10 years was not associated with sleep duration or insomnia symptoms. However, compared with those with decreasing aMed score, individuals with an unchanging score reported fewer insomnia symptoms (p ≤ 0.01). These results suggest that a Mediterranean-style diet is associated with adequate sleep duration, less insomnia symptoms, and less likely to have insomnia accompanied by short sleep. Further research should identify possible mediators through which diet may promote adequate sleep duration and reduce the risk of insomnia.
Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. ...We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality.
We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium ln (CAC+1) and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval CI 0.11, 0.39). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios HR per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively).
In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.
The drivers of sexual dimorphism in heart failure phenotypes are currently poorly understood. Divergent phenotypes may result from differences in heritability and genetic versus environmental ...influences on the interplay of cardiac structure and function. To assess sex-specific heritability and genetic versus environmental contributions to variation and inter-relations between echocardiography traits in a large community-based cohort. We studied Framingham Heart Study participants of Offspring Cohort examination 8 (2005-2008) and Third Generation Cohort examination 1 (2002-2005). Five cardiac traits and six functional traits were measured using standardized echocardiography. Sequential Oligogenic Linkage Analysis Routines (SOLAR) software was used to perform singular and bivariate quantitative trait linkage analysis. In our study of 5674 participants (age 49 ± 15 years; 54% women), heritability for all traits was significant for both men and women. There were no significant differences in traits between men and women. Within inter-trait correlations, there were two genetic, and four environmental trait pairs with sex-based differences. Within both significant genetic trait pairs, men had a positive relation, and women had no significant relation. We observed significant sex-based differences in inter-trait genetic and environmental correlations between cardiac structure and function. These findings highlight potential pathways of sex-based divergent heart failure phenotypes.
It is well established that coronary artery disease progresses along with myocardial disease. However, data on the association between coronary artery calcium (CAC) and echocardiographic variables ...are lacking.
Among 2,650 Framingham Study participants (mean age 51 yrs, 48% women; 40% with CAC>0), we related CT-based CAC score to left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), E/e', global longitudinal strain (GLS), left atrial emptying fraction (LAEF), and aortic root diameter (AoR), using multivariable-adjusted generalized linear models. CAC score (independent variable) was used as log-transformed continuous ln(CAC+1) and as a categorical (0, 1-100, and ≥101) variable. Adjusting for standard risk factors, higher CAC score was associated with higher LVMi and AoR (βLVMI per 1-SD increase 0.012, βAoR 0.008; P<0.05, for both). Participants with 1≤CAC≤100 and those with CAC≥101 had higher AoR (βAoR 0.013 and 0.020, respectively, P = 0.01) than those with CAC = 0. CAC score was not significantly associated with LVEF, E/e', GLS or LAEF. Age modified the association of CAC score with AoR; higher CAC scores were associated with larger AoR more strongly in older (>58 years; βAoR0.0042;P<0.007) than in younger (≤58 years) participants (βAoR0.0027;P<0.03).
We observed that subclinical atherosclerosis was associated with ventricular and aortic remodeling. The prognostic significance of these associations warrants evaluation in additional mechanistic studies.
Cardiac and vascular growth factors (GF) may influence myocardial remodeling through cardiac growth and angiogenic effects. We hypothesized that concentrations of circulating GF are associated with ...cardiac remodeling traits.
We related blood concentrations of vascular endothelial GF (VEGF), VEGFR-1 (sFlt1), angiopoietin 2 (Ang-2), soluble angiopoietin type-2 receptor (sTie2), hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, and growth differentiation factor-15 (GDF-15) to echocardiographic traits in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following measures: left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', and aortic root diameter (AoR). All biomarker values were sex-standardized.
In multivariable-adjusted analyses, higher GDF-15 concentrations were associated with higher log-LVMi (β = 0.009 per SD, P = 0.01). Similarly, sTie2 concentrations were positively associated with log-E/e' (β = 0.011 per SD, P = 0.04). IGF-1 and Ang-2 concentrations were positively and negatively associated with GLS, respectively (βIGF-1 = 0.16 per SD and βAng-2 = −0.15 per SD, both P < 0.05), whereas higher sFlt1 and Ang-2 levels were associated with smaller log-AoR (βsFlt1 = −0.004 per SD and β Ang-2 = −0.005 per SD, respectively; P < 0.05).
In our large community-based sample, we observed patterns of associations between several circulating vascular GF and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional studies are warranted to replicate our findings and assess their prognostic significance.
•There are patterns of associations between several circulating vascular GF and cardiac remodeling.•The findings are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries.•Additional studies are warranted to replicate our findings and assess their prognostic significance.
Background:
Short telomere length (TL) and telomere attrition (TA) have been associated with age-related diseases.
Objective:
We assessed whether a genetic risk score for short TL (GRS-TL) combining ...seven TL-associated genetic variants identified in a European-ancestry genome-wide association study (GWAS) was associated with TL and TA over 10 years.
Methods:
Relative TL (T/S ratio) was measured by the quantitative polymerase chain reaction method for a sample of white, African American, and Hispanic participants, who attended Exam 1 and/or 5 of the Multi-Ethnic Study of Atherosclerosis (MESA). Our final sample included 1,227 participants for the TL analysis and 1,138 for the TA analysis. Participants were 45–84 years at Exam 1. We used a linear mixed effects model and adjusted for age, sex, and population structure. Models were stratified by race/ethnicity.
Results:
In the TL analysis, higher GRS-TL significantly predicted shorter TL (estimates = -0.18 S.E. = 0.08,
p
= 0.02 for white; -0.18 0.07,
p
< 0.01 for African American; and -0.13 0.05,
p
= 0.02 for Hispanic) in fully adjusted models. In the TA analysis, no association between GRS-TL and TA over 10 years was found.
Conclusion:
Although GRS-TL was developed in European-ancestry populations, it was significantly associated with TL (but not TA) in all three race/ethnic groups examined.
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