BACKGROUND: Despite evidence that African Americans shoulder a high burden of mobility limitation, little is known about factors associated with recovery. METHOD: Participants from the Jackson Heart Study underwent 3 in-person exams from 2000 to 2013. Mobility limitations were assessed over this period by self-reported limitations in walking half a mile or climbing stairs during annual phone calls. The outcome of interest, recovery from mobility limitation, was defined as no mobility limitation the year following an incident event. Candidate predictor variables were assessed in logistic regression models, including sociodemographic, psychosocial, and health measures. Inverse probability weights were used to address missing data in the outcome. RESULTS: Among 4526 participants (mean [SD] age = 54.5 (12.8) years) without a mobility limitation at baseline, 1445 (32%) had an incident mobility limitation over 12 years of follow-up, and 709 (49%) reported recovery from mobility limitation by 1 year later. Low income and daily discrimination were associated with a lower likelihood of recovery even after adjustment for covariates. In adjusted models, greater comorbidity was associated with a lower likelihood of recovering (p-value for trend = .05). History of heart failure and cancer were associated with a lower likelihood of recovering from mobility limitation (OR: 0.52, 95% CI: 0.29, 0.94 and OR: 0.74, 95% CI: 0.55, 1.00). Adiposity, smoking status, and physical activity were not associated with recovery from mobility limitation. CONCLUSION: Half of incident mobility limitations in this population of middle-aged African Americans were transient. Adverse sociodemographic factors and comorbidities were associated with lower likelihood of recovery.

Objective

African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA.

Research design and methods

We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA_1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data.

Results

During 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile (<1.46 mg/L); P < 0.001. Participants with high hs-CRP had higher incidence of DN (HR 2.34, 95% CI 1.04-5.24) versus the reference group.

Conclusions

Inflammation, as measured by hs-CRP levels, may be associated with incident DN in AA. Further studies are warranted to replicate and elucidate the basis for this association.

Objective

Controlling cardiovascular disease (CVD) risk factors in diabetes mellitus (DM) reduces the number of CVD events, but the effects of multifactorial risk factor control are not well quantified. We examined whether being at targets for blood pressure (BP), LDL cholesterol (LDL-C), and glycated hemoglobin (HbA1c) together are associated with lower risks for CVD events in U.S. adults with DM.

Research design and methods

We studied 2,018 adults, 28-86 years of age with DM but without known CVD, from the Atherosclerosis Risk in Communities (ARIC) study, Multi-Ethnic Study of Atherosclerosis (MESA), and Jackson Heart Study (JHS). Cox regression examined coronary heart disease (CHD) and CVD events over a mean 11-year follow-up in those individuals at BP, LDL-C, and HbA1c target levels, and by the number of controlled risk factors.

Results

Of 2,018 DM subjects (43% male, 55% African American), 41.8%, 32.1%, and 41.9% were at target levels for BP, LDL-C, and HbA1c, respectively; 41.1%, 26.5%, and 7.2% were at target levels for any one, two, or all three factors, respectively. Being at BP, LDL-C, or HbA1c target levels related to 17%, 33%, and 37% lower CVD risks and 17%, 41%, and 36% lower CHD risks, respectively (P < 0.05 to P < 0.0001, except for BP in CHD risk); those subjects with one, two, or all three risk factors at target levels (vs. none) had incrementally lower adjusted risks of CVD events of 36%, 52%, and 62%, respectively, and incrementally lower adjusted risks of CHD events of 41%, 56%, and 60%, respectively (P < 0.001 to P < 0.0001). Propensity score adjustment showed similar findings.

Conclusions

Optimal levels of BP, LDL-C, and HbA1c occurring together in individuals with DM are uncommon, but are associated with substantially lower risk of CHD and CVD.

Background

Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. The authors seek to examine to what extent periodontal disease is associated with kidney function decline.

Methods

This retrospective cohort study examines 699 African American participants with preserved kidney function (defined by estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73 m(2) at baseline) who underwent complete dental examinations as part of the Dental-Atherosclerosis Risk in Communities study (1996 to 1998) and subsequently enrolled in the Jackson Heart Study (2000 to 2004). Using multivariable Poisson regression, the authors examined the association of periodontal disease (severe versus non-severe) with incident CKD, defined as incident eGFR <60 mL/minute/1.73 m(2) and rapid (5% annualized) eGFR decline at follow-up among those with preserved eGFR at baseline.

Results

Mean (± SD) age at baseline was 65.4 (± 5.2) years, and 16.3% (n = 114) had severe periodontal disease. There were 21 cases (3.0%) of incident CKD after a mean follow-up of 4.8 (± 0.6) years. Compared with participants with non-severe periodontal disease, those with severe periodontal disease had a four-fold greater rate of incident CKD (adjusted incidence rate ratio 4.18 [95% confidence interval 1.68 to 10.39], P = 0.002).

Conclusions

Severe periodontal disease is prevalent among a population at high risk for CKD and is associated with clinically significant kidney function decline. Further research is needed to determine if periodontal disease treatment alters the trajectory of renal deterioration.

Importance

Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Understanding the relative contributions of cardiovascular disease event types to the excess burden of cardiovascular disease is important for developing effective strategies to improve outcomes.

Objective

To determine absolute rates and risk differences of incident heart failure (HF), coronary heart disease (CHD), and stroke in participants with vs without CKD.

Design, setting and participants

We pooled participants without prevalent cardiovascular disease from 3 community-based cohort studies: the Jackson Heart Study, Cardiovascular Health Study, and Multi-Ethnic Study of Atherosclerosis. The Jackson Heart Study was conducted between 2000 and 2010, the Cardiovascular Health Study was conducted between 1989 and 2003, and the Multi-Ethnic Study of Atherosclerosis was conducted between 2000 and 2012.

Exposures

Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2, calculated using the combined creatinine-cystatin C CKD-Epidemiology Collaboration Equation.

Main outcomes and measures

Poisson regression was used to calculate incidence rates (IRs) and risk differences of adjudicated incident HF, CHD, and stroke, comparing participants with vs without CKD.

Results

Among 14 462 participants, the mean (SD) age was 63 (12) years, 59% (n = 8533) were women, and 44% (n = 6363) were African American. Overall, 1461 (10%) had CKD (mean [SD] estimated glomerular filtration rate, 49 [10] mL/min/1.73 m2). Unadjusted IRs for participants with and without CKD, respectively, were 22.0 (95% CI, 19.3-24.8) and 6.2 (95% CI, 5.8-6.7) per 1000 person-years for HF; 24.5 (95% CI, 21.6-27.5) and 8.4 (95% CI, 7.9-9.0) per 1000 person-years for CHD; and 13.4 (95% CI, 11.3-15.5) and 4.8 (95% CI, 4.4-5.3) for stroke. Adjusting for demographics, cohort, hypertension, diabetes, hyperlipidemia, and tobacco use, risk differences comparing participants with vs without CKD (per 1000 person-years) were 2.3 (95% CI, 1.2-3.3) for HF, 2.3 (95% CI, 1.2-3.4) for CHD, and 0.8 (95% CI, 0.09-1.5) for stroke. Among African American and Hispanic participants, adjusted risk differences comparing participants with vs without CKD for HF were 3.5 (95% CI, 1.5-5.5) and 7.8 (95% CI, 2.2-13.3) per 1000 person-years, respectively.

Conclusions and relevance

Among 3 diverse community-based cohorts, CKD was associated with an increased risk of HF that was similar in magnitude to CHD and greater than stroke. The excess risk of HF associated with CKD was particularly large among African American and Hispanic individuals. Efforts to improve health outcomes for patients with CKD should prioritize HF in addition to CHD prevention.

Background

Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population.

Study design

Prospective cohort study.

Setting & participants

3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation.

Predictors

Demographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure.

Outcomes

Rapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models.

Measurements

Clinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors.

Results

Mean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline.

Limitations

No midstudy creatinine measurement at examination 2 (2005-2008).

Conclusions

Rapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.

Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.

Although type 2 diabetes (T2D) results from metabolic defects in insulin secretion and insulin sensitivity, most of the genetic risk loci identified to date relates to insulin secretion. We reported that T2D loci influencing insulin sensitivity may be identified through interactions with insulin secretion loci, thereby leading to T2D. Here, we hypothesize that joint testing of variant main effects and interaction effects with an insulin secretion locus increases power to identify genetic interactions leading to T2D. We tested this hypothesis with an intronic MTNR1B SNP, rs10830963, which is associated with acute insulin response to glucose, a dynamic measure of insulin secretion. rs10830963 was tested for interaction and joint (main + interaction) effects with genome-wide data in African Americans (2,452 cases and 3,772 controls) from five cohorts. Genome-wide genotype data (Affymetrix Human Genome 6.0 array) was imputed to a 1000 Genomes Project reference panel. T2D risk was modeled using logistic regression with rs10830963 dosage, age, sex, and principal component as predictors. Joint effects were captured using the Kraft two degrees of freedom test. Genome-wide significant (P < 5 × 10^-8 ) interaction with MTNR1B and joint effects were detected for CMIP intronic SNP rs17197883 (P_interaction  = 1.43 × 10^-8 ; P_joint  = 4.70 × 10^-8 ). CMIP variants have been nominally associated with T2D, fasting glucose, and adiponectin in individuals of East Asian ancestry, with high-density lipoprotein, and with waist-to-hip ratio adjusted for body mass index in Europeans. These data support the hypothesis that additional genetic factors contributing to T2D risk, including insulin sensitivity loci, can be identified through interactions with insulin secretion loci.

Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction<5×10-6) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci.