Dataset Information

Lifestyle factors and indices of kidney function in the Framingham Heart Study.

ABSTRACT: BACKGROUND AND OBJECTIVES:Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) and rapid eGFR decline in older adults in the United States. METHODS:Prospective cohort study of Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m(2) (n = 1,802) who attended the seventh (1998-2001; baseline) and eighth (2005-2008; follow-up) examinations (mean age = 59 years, 54.8% women). Predictors included measures of diet quality, physical activity, alcohol intake, and current smoking status assessed during baseline. Outcomes were based on creatinine-based eGFR at baseline and follow-up and included incident eGFR <60 ml/min/1.73 m(2) (at follow-up) and rapid eGFR decline (annual eGFR decrease ?3 ml/min/1.73 m(2)). RESULTS:Over an average follow-up of 6.6 years, 9.5% (n = 171) of participants developed incident eGFR <60. A trend was observed across quartiles of diet quality, with higher levels of diet quality associated with a decreased odds ratio (OR) of incident eGFR <60 (p trend = 0.045). Higher diet quality was associated with decreased odds of rapid eGFR decline (p trend = 0.03) and was attenuated with additional adjustment (p trend = 0.07). In sensitivity analysis for rapid eGFR decline using a secondary definition (annual eGFR decrease ?3 and incident eGFR <60), diet associations remained significant with additional adjustment (p trend = 0.04). No associations were observed with physical activity, smoking status, or alcohol intake with incident eGFR <60 or rapid eGFR decline (all p > 0.19). CONCLUSIONS:Higher diet quality may be associated with a decreased risk of incident eGFR <60 ml/min/1.73 m(2), and rapid eGFR decline. Whether adherence to a healthy diet can prevent reduction in kidney function warrants further study.

SUBMITTER: Foster MC

PROVIDER: S-EPMC4514559 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Lifestyle factors and indices of kidney function in the Framingham Heart Study.

Foster Meredith C MC Hwang Shih-Jen SJ Massaro Joseph M JM Jacques Paul F PF Fox Caroline S CS Chu Audrey Y AY

American journal of nephrology 20150520 4-5

<h4>Background and objectives</h4>Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) and rapid eGFR decline in older adults in the United States.<h4>Methods</h4>Prospective cohort study of Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m(2) (n = 1,802) who a ...[more]

PMID: 25998023

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Project description:Background Data are limited on the association of mildly reduced estimated glomerular filtration rate (eGFR 60-89 mL/min per 1.73 m2) with cardiovascular disease (CVD) in the community. Methods and Results We evaluated 3066 Framingham Offspring Study participants (55% women, mean age 58 years), without clinical CVD. Using multivariable regression, we related categories of mildly reduced eGFR (80-89, 70-79, or 60-69 versus ≥90 mL/min per 1.73 m2 [referent]) to prevalent coronary artery calcium, carotid intima media thickness, and left ventricular hypertrophy, and to circulating concentrations of cardiac stress biomarkers. We related eGFR categories to CVD incidence and to progression to ≥Stage 3 chronic kidney disease (eGFR <60 mL/min per 1.73 m2) using Cox regression. Individuals with eGFR 60-69 mL/min per 1.73 m2 (n=320) had higher coronary artery calcium score (odds ratio 1.69; 95% CI 1.02-2.80) compared with the referent group. Individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 had higher blood growth differentiating factor-15 concentrations (β=0.131 and 0.058 per unit-increase in log-biomarker, respectively). Participants with eGFR 60-69 and 80-89 mL/min per 1.73 m2 had higher blood B-type natriuretic peptide concentrations (β=0.119 and 0.116, respectively). On follow-up (median 16 years; 691 incident CVD and 252 chronic kidney disease events), individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 experienced higher CVD incidence (hazard ratio [HR], 1.40; 95% CI, 1.02-1.93 and 1.45, 95% CI, 1.05-2.00, respectively, versus referent). Participants with eGFR 60-69 mL/min per 1.73 m2 experienced higher chronic kidney disease incidence (HR, 2.94; 95% CI, 1.80-4.78 versus referent). Conclusions Individuals with mildly reduced eGFR 60-69 mL/min per 1.73 m2 have a higher burden of subclinical atherosclerosis cross-sectionally, and a greater risk of CVD and chronic kidney disease progression prospectively. Additional studies are warranted to confirm our findings.

Project description:BackgroundBiomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases.MethodsWe evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3 (cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function.ResultsIn cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p = 5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p = 0.0001) concentration with eGFR.Discussion/conclusionsEight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Project description:Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP) set and measures of kidney function and endocrine traits.Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981) were measured at the seventh examination cycle (1998-2001); GFR (n = 1010) was estimated via the Modification of Diet in Renal Disease (MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle (1995-1998) and was indexed to urinary creatinine (n = 822). Thyroid stimulating hormone (TSH) was measured at the third and fourth examination cycles (1981-1984; 1984-1987) and mean value of the measurements were used (n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE) and family-based association tests (FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value > or = 0.001, and call rates of at least 80%.The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10(-05)), rs1158167 with cysC (p-value 8.5*10(-09)), rs1712790 with UAE (p-value 1.9*10(-06)), and rs6977660 with TSH (p-value 3.7*10(-06)), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10(-5)), rs563754 with cysC (p-value 4.7*10(-5)), rs1243400 with UAE (p-value 4.8*10(-6)), and rs4128956 with TSH (p-value 3.6*10(-5)), respectively. Detailed association test results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. Four SNPs in or near the CST3 gene were highly associated with cysC levels (p-value 8.5*10(-09) to 0.007).Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.

Project description:BackgroundThere have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF).ObjectiveWe evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study.DesignParticipants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression.ResultsA total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n-3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001).ConclusionsConsumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population.

Project description:IMPORTANCE:Dyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies. OBJECTIVE:To examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015. EXPOSURES:Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels. MAIN OUTCOMES AND MEASURES:Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL). RESULTS:Among the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (??=?0.32 [SE, 0.05] mg/dL; P?<?.001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P?=?.005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels. CONCLUSIONS AND RELEVANCE:Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.

Project description:Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25-75), the FEV1/FVC ratio, and the FEF25-75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency > or = 10%, genotype call rate > or = 80%, and Hardy-Weinberg equilibrium p-value > or = 0.001. A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25-75. A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

Dataset Information

Lifestyle factors and indices of kidney function in the Framingham Heart Study.

Publications

Lifestyle factors and indices of kidney function in the Framingham Heart Study.

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