NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and ...examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).
Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.
In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
The aim of this study was to determine whether displacement of sedentary time with activity was cross‐sectionally associated with less adiposity among Black Caribbean men in the Tobago ...Health Study.
Methods
Objectively assessed activity was categorized as sedentary (< 1.5 metabolic equivalents; METs), light (≥ 1.5 to < 3.0 METs), or moderate‐to‐vigorous (≥ 3.0 METs) using the SenseWear Pro armband. Computed tomography scans of the chest, abdomen, liver, and thigh were used to assess subcutaneous and ectopic adipose tissue. The isotemporal substitution framework paired with linear regression was used to examine associations between activity and adiposity adjusting for age, height, total awake time, and multiple comparisons.
Results
On average, participants (n = 271) were 63 years old with 11.2 h/d of sedentary behavior, 4.5 h/d of light activity, and 54 min/d of moderate‐to‐vigorous activity. Replacing sedentary time with light activity was cross‐sectionally associated with lower volume and higher density of abdominal and thigh subcutaneous adiposity, visceral adiposity, abdominal and thigh intermuscular adiposity, and pericardial adiposity and higher liver attenuation (p values ≤ 0.0001).
Conclusions
Displacement of sedentary time with light activity was associated with less adiposity among this Black Caribbean cohort. Interventions focused on increasing light activity may be easier to maintain than higher intensity interventions and thus may be more successful at reducing adiposity.
Abstract
Background
Sarcopenia varies by ethnicity, and has a major impact on health in older adults. However, little is known about sarcopenia characteristics in African ancestry populations outside ...the United States. We examined sarcopenia characteristics in 2,142 African Caribbean men aged 59.0 ± 10.4 years (range: 40–92 years) in Tobago, and their association with incident mobility limitations in those aged 55+ (n = 738).
Methods
Body mass index (BMI), grip strength, dual-x-ray absorptiometry (DXA) appendicular lean mass (ALM), and self-reported mobility limitations were measured at baseline, and 6 years later. Change in sarcopenia characteristics, including grip strength, grip strength/BMI, ALMBMI, and ALM/ht2, were determined. Foundations for the National Institutes of Health Sarcopenia Project (FNIH) and European Working Group for Sarcopenia in Older People 2 (EWGSOP2) cut-points were also examined. Odds ratios (OR) and 95% confidence intervals (CI) for mobility limitation were calculated using multivariable linear regression models adjusted for covariates.
Results
Overall, sarcopenia prevalence was quite low using the FNIH (0.3%) and EWGSOP2 (0.6%) operational cut-points, but was higher in those aged 75+ (2.1% FNIH and 3.7% EWGSOP2). Prevalence was also higher when based on “weakness”, versus “low ALM.” When sarcopenia markers were examined separately, baseline levels, but not changes, were associated with incident mobility limitations. Baseline grip strength/BMI was a particularly strong risk factor for incident mobility limitations (OR per SD: 0.50; 95% CI: 0.37–0.68).
Conclusions
Our findings suggest that grip strength normalized to body mass, measured at one time point, may be a particularly useful phenotype for identifying African Caribbean men at risk for future mobility limitations.
Abstract
Background
Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was ...associated with baseline and 7-year change in physical function.
Method
Participants (n = 400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay coefficient of variation <5.5%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (SPPB score 0–12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log-transformed P3NP and physical function was examined using generalized estimating equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, liver function, kidney function, lung function, and chronic disease prevalence.
Results
Participants were aged 73.1 ± 15.2 years (range: 39–104), 54% female, had body mass index of 26.6 ± 4.3 kg/m2, and gait speeds of 1.0 ± 0.3 m/s. One standard deviation higher log-transformed P3NP was related to worse baseline SPPB score (β = −0.9points), gait speed (β = −0.05m/s), chair-rises per-second (β = −0.46chair-rises/10 seconds), and grip strength (β = −2.0kg; all p < .001). Higher P3NP was also associated with greater declines in gait speed (β = −1.41, p < .001) and transitioning to being unable to perform chair-rises (β = 0.41, p < .001) after 7 years.
Conclusion
Plasma P3NP may be a strong, novel biomarker of current and future physical function. Future research is needed to extend our findings to other cohorts and determine mechanisms underlying these associations.
Objective
Skeletal muscle adiposity (myosteatosis) is recognized as a major risk factor for cardiometabolic diseases, and it increases with aging. The relationship of myosteatosis with cognitive ...impairment is unknown.
Methods
The association of calf myosteatosis (measured by computed tomography‐derived skeletal muscle density; higher values indicate less myosteatosis) with cognitive function was examined among 626 African Caribbean women who were aged 40 to 84 years, a population highly vulnerable to increased myosteatosis. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed (higher scores indicate better performance). Linear regression was used to assess the association of muscle density with DSST.
Results
Adjusting for age, education, muscle area, BMI, hypertension, diabetes, cardiovascular event history, lifestyle factors, lipid‐lowering medication use, and menopausal status, a one‐SD lower muscle density was associated with a 1.69‐point lower DSST score (p = 0.002). BMI, diabetes, and hypertension interactions were not statistically significant, suggesting that the main association was not moderated by overall obesity or cardiometabolic diseases.
Conclusions
These findings suggest that greater myosteatosis is associated with slower information processing speed, an early indicator of cognitive impairment. Further studies are needed to establish this association in this and other populations using an expanded battery of cognitive tests with longitudinal follow‐up and to identify the biological mechanisms underlying this relationship.
Abstract
Background
African Caribbeans have higher levels of myosteatosis than other populations; however, little is known about the impact of myosteatosis on physical function in African Caribbeans. ...Herein, we examined the association between regional myosteatosis of the calf, thigh, and abdomen versus physical function in 850 African-Ancestry men aged 64.2 ± 8.9 (range 50–95) living on the Caribbean Island of Tobago.
Methods
Myosteatosis was measured using computed tomography and included intermuscular adipose tissue (IMAT) and muscle density levels of the thigh, calf, psoas, and paraspinous muscles. Outcomes included grip strength, time to complete 5 chair-rises, and 4-meter gait speed. Associations were quantified using separate linear models for each myosteatosis depot and were adjusted for age, height, demographics, physical activity, and chronic diseases. Beta coefficients were presented per standard deviation of each myosteatosis depot.
Results
Higher thigh IMAT was the only IMAT depot significantly associated with weaker grip strength (β = −1.3 ± 0.43 kg, p = .003). However, lower muscle density of all 4 muscle groups was associated with weaker grip strength (all p < .05). Calf and thigh myosteatosis (IMAT and muscle density) were significantly associated with both worse chair rise time and gait speed (all p < .05), whereas psoas IMAT and paraspinous muscle density were associated with gait speed.
Conclusion
Myosteatosis of the calf and thigh―but not the abdomen―were strongly associated with grip strength and performance measures of physical function in African Caribbean men. However, posterior abdominal myosteatosis may have some utility when abdominal images are all that are available.
Abstract
Background
Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is ...associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry.
Methods
Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models.
Results
Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio OR: 1.60; 95% confidence interval CI: 1.21–2.13; OR: 1.51; 95% CI: 1.18–1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48–0.87).
Conclusions
Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.
Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential ...genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men).
Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center.
At baseline, 26.9% of individuals had "slow" gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p < .0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p < .05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene.
Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.
Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in humans is lacking. We examined ...peripheral blood Wnt pathway gene expression and arterial stiffness in 369 healthy African ancestry men (mean age, 64 years). Methods and Results Gene expression was assessed using a custom Nanostring nCounter gene expression panel (N=43 genes) and normalized to housekeeping genes and background signal. Arterial stiffness was assessed via brachial-ankle pulse-wave velocity. Fourteen Wnt genes showed detectable expression and were tested individually as predictors of pulse-wave velocity using linear regression, adjusting for age, height, weight, blood pressure, medication use, resting heart rate, current smoking, alcohol intake, and sedentary lifestyle. Adenomatous polyposis coli regulator of Wnt signaling pathway (
), glycogen synthase kinase 3β (
), and transcription factor 4 (
) were significantly associated with arterial stiffness (
<0.05 for all). When entered into a single model,
and
expression remained independently associated with arterial stiffness (
=0.04 and 0.003, respectively), and each explained ≈3% of the variance in pulse-wave velocity. Conclusions The current study establishes a novel association between in vivo expression of the Wnt pathway genes,
and
, with arterial stiffness in African ancestry men, a population at high risk of hypertensive vascular disease.
This study tested the association of objectively measured physical activity with blood pressure and hypertension in African Caribbean men, an understudied population segment known to be at high-risk ...for cardiovascular disease (CVD) which has low levels of high-exertion physical activity. Men (N = 310) were from the Tobago Health Study and aged 50–89 years. Systolic (SBP) and diastolic (DBP) blood pressures were measured using an automated device, and hypertension was defined as SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or current use of antihypertensive medication. Physical activity was measured using the SenseWear Pro armband (SWA) and consisted of daily time engaged in sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous activity (MVPA), as well as daily step count. Multiple regression analyses using the isotemporal substitution framework were used to test for associations between activity and blood pressures. Models were adjusted in stages for SWA wear time, age, antihypertensive medication use, alcohol consumption, smoking, diabetes, CVD, family history of hypertension, salt intake, and adiposity.
Replacement of SB with LPA was associated with lower SBP adjusted for wear time (β = -0.84, p < 0.05), but attenuated after adjustment for age. Replacement of SB with LPA was associated with lower DBP (β = -0.50) and lower odds of hypertension (OR = 0.88), adjusted for wear time and age (both p < 0.05). All model associations of replacement of SB with LPA were stronger when restricted to men not taking antihypertensive medications, regardless of their hypertension status.
These results support the strategy of increasing light physical activity for blood pressure management in high-risk Afro-Caribbean men.
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