Showing papers by "Barbara V. Howard published in 2014"
TL;DR: Findings suggest a nonlinear association between LTL and incident diabetes and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes.
Abstract: Telomeres play a central role in cellular aging, and shorter telomere length has been associated with age-related disorders including diabetes. However, a causal link between telomere shortening and diabetes risk has not been established. In a well-characterized longitudinal cohort of American Indians participating in the Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at baseline predicts incident diabetes independent of known diabetes risk factors. Among 2,328 participants free of diabetes at baseline, 292 subjects developed diabetes during an average 5.5 years of follow-up. Compared with subjects in the highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an almost twofold increased risk of incident diabetes (hazard ratio [HR] 1.83 [95% CI 1.26–2.66]), whereas the risk for those in the second (HR 0.87 [95% CI 0.59–1.29]) and the third (HR 0.95 [95% CI 0.65–1.38]) quartiles was statistically nonsignificant. These findings suggest a nonlinear association between LTL and incident diabetes and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes.
140 citations
TL;DR: The adoption of as few as two or three Life’s Simple 7 goals is associated with a lower risk of diabetes, and those who achieved 2–3 or 4+ goals had lower odds of diabetes.
Abstract: OBJECTIVE The American Heart Association’s recommendations for optimal health, summarized in Life’s Simple 7, have been associated with reduced risk of cardiovascular disease (CVD)-related end points, but no studies have examined the association of these goals with incident type 2 diabetes, which is associated with high risk for CVD. The purpose of this analysis was to examine the associations of Life’s Simple 7 goals with incident diabetes among American Indians, a population at high risk of cardiometabolic diseases. RESEARCH DESIGN AND METHODS Strong Heart Family Study participants without diabetes ( n = 1,639) at baseline and who participated in a follow-up examination were included in the analysis. Risk scores ranging from 0 to 7 were created using physical activity, diet, BMI, smoking, blood pressure, fasting glucose, and cholesterol metrics in accordance with Life’s Simple 7 goals. Diabetes was defined using 2003 American Diabetes Association criteria, including use of insulin or oral antidiabetes medication or a follow-up fasting plasma glucose level ≥126 mg/dL. Generalized estimating equations were used to examine the association of risk scores with incident diabetes. RESULTS During a mean 5-year follow-up (range 4–8 years), we identified 210 cases of incident type 2 diabetes. Compared with participants who achieved 0–1 goals, those who achieved 2–3 or 4+ goals had lower odds of diabetes, with odds ratios = 0.40 (95% CI 0.29–0.56) and 0.11 (95% CI 0.05–0.21), respectively. CONCLUSIONS The adoption of as few as two or three Life’s Simple 7 goals is associated with a lower risk of diabetes.
82 citations
15 May 2014
TL;DR: In this paper, the authors examined the association of leukocyte telomere length (LTL) with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waistto-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study.
Abstract: Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.
56 citations
28 May 2014
TL;DR: In this paper, the authors examined whether short leukocyte telomere length (LTL) at baseline predicts incidence and progression of carotid atherosclerosis in American Indians in the Strong Heart Study.
Abstract: Short leukocyte telomere length (LTL) has been associated with atherosclerosis in cross-sectional studies, but the prospective relationship between telomere shortening and risk of developing carotid atherosclerosis has not been well-established. This study examines whether LTL at baseline predicts incidence and progression of carotid atherosclerosis in American Indians in the Strong Heart Study. The analysis included 2,819 participants who were free of overt cardiovascular disease at baseline (2001-2003) and were followed through the end of 2006-2009 (average 5.5-yr follow-up). Discrete atherosclerotic plaque was defined as focal protrusion with an arterial wall thickness ≥50% the surrounding wall. Carotid progression was defined as having a higher plaque score at the end of study follow-up compared to baseline. Associations of LTL with incidence and progression of carotid plaque were examined using Cox proportional hazard regression, adjusting for standard coronary risk factors. Compared to participants in the highest LTL tertile, those in the lowest tertile had significantly elevated risk for both incident plaque (HR, 1.49; 95% CI, 1.09-2.03) and plaque progression (HR, 1.61; 95% CI, 1.26-2.07). Our results provide initial evidence for a potential prognostic utility of LTL in risk prediction for atherosclerosis.
55 citations
01 Jan 2014
TL;DR: Initial evidence is provided for a potential prognostic utility of LTL in risk prediction for atherosclerosis in American Indians in the Strong Heart Study.
Abstract: Short leukocyte telomere length (LTL) has been associated with atherosclerosis in cross-sectional studies, but the prospective relationship between telomere shortening and risk of developing carotid atherosclerosis has not been well-established. This study examines whether LTL at baseline predicts incidence and progression of carotid atherosclerosis in American Indians in the Strong Heart Study. The analysis included 2,819 participants who were free of overt cardiovascular disease at baseline (2001-2003) and were followed through the end of 2006-2009 (average 5.5-yr follow-up). Discrete atherosclerotic plaque was defined as focal protrusion with an arterial wall thickness ≥50% the surrounding wall. Carotid progression was defined as having a higher plaque score at the end of study follow-up compared to baseline. Associations of LTL with incidence and progression of carotid plaque were examined using Cox proportional hazard regression, adjusting for standard coronary risk factors. Compared to participants in the highest LTL tertile, those in the lowest tertile had significantly elevated risk for both incident plaque (HR, 1.49; 95% CI, 1.09–2.03) and plaque progression (HR, 1.61; 95% CI, 1.26–2.07). Our results provide initial evidence for a potential prognostic utility of LTL in risk prediction for atherosclerosis.
55 citations
Journal Article•
TL;DR: Examination of the association of LTL with obesity indices in 3,256 American Indians for the first time shows that obese participants had significantly shorter LTL than non-obese individuals, and may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.
Abstract: Background: Obesity is an independent risk factor for diabetes and cardiovascular disease. Telomere length shortens progressively with age, and shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders. However, the association between LTL and obesity has not been well established. Objective: To examine the association of LTL with obesity and related traits in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003), independent of known risk factors. Methods: A total of 3,162 participants (18-93 years old, 1,938 women) from 94 multigenerational families were included in this analysis. Obesity-related traits included body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. LTL was measured by quantitative PCR. Association of LTL (continuous or in quintiles) with each adiposity index was examined using generalized linear mixed model, adjusting for age, sex, study center, education, lifestyle factors (current...
43 citations
TL;DR: In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation, but UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.
Abstract: Aim To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS) cohort. Methods and results In this population-based prospective study we analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam. Participants were divided into sex-specific tertiles of UA and the first two tertiles (group N) were compared with the third tertile (group H). Body mass index (BMI = 28.3 ± 7 vs. 31.1 ± 7 kg/m 2 ), fat-free mass (FFM = 52.0 ± 14 vs. 54.9 ± 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices of inflammation were significantly higher in group H than in group N (all p p p = 0.04) independently of family relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal function, but disappeared when fat-free mass was included in the model. Conclusions In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation. UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.
35 citations
Harvard University1, University of California, Los Angeles2, Stanford University3, Fred Hutchinson Cancer Research Center4, National Institutes of Health5, Georgetown University6, University of Arizona7, University at Buffalo8, Ohio State University9, University of Florida10, Regions Hospital11, Yeshiva University12, University of Pittsburgh13, Brown University14, Case Western Reserve University15, AstraZeneca16, University of Tennessee Health Science Center17, University of Alabama at Birmingham18, George Washington University19, University of Massachusetts Medical School20, University of Miami21, Rush University Medical Center22, Wayne State University23, Northwestern University24, Wake Forest University25, University of Iowa26
TL;DR: The results from the intervention and extended post-intervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women as discussed by the authors.
Abstract: RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.781.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10 000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.
31 citations
TL;DR: Regular use of selective co-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events, and this harmful association remained among concomitant aspirin users.
Abstract: Background—Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition. Methods and Results—Postmenopausal women enrolled in the Women’s Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were availab...
23 citations
University of North Carolina at Chapel Hill1, Emory University2, University of Washington3, Wake Forest University4, Rutgers University5, National Institutes of Health6, Johns Hopkins University7, Texas Biomedical Research Institute8, Memorial Hospital of South Bend9, Fred Hutchinson Cancer Research Center10, George Washington University11, University of Tennessee Health Science Center12, Erasmus University Rotterdam13, Northwestern University14, Harvard University15, University of Texas Health Science Center at Houston16
TL;DR: The findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
Abstract: Background
Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.
Methods and Results
Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1×10−8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.
Conclusions
Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
23 citations
TL;DR: This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries.
Abstract: Summary Background and objectives CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. Design, setting, participants, & measurements This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. Results This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B ,a ndWDR72 (P,2.1 3 10 -3 to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. Conclusion This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries. Clin J Am Soc Nephrol 9: 150–158, 2014. doi: 10.2215/CJN.02300213
20 Mar 2014
TL;DR: In this paper, the authors examined the metabolome of telomeric aging in human subjects and found that nineteen metabolites in the classes of glycerophosphoethanolamines (GPHs), glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were associated with LTL, independent of chronological age and other aging-related factors.
Abstract: Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.
TL;DR: RFFMD in overweight/obese normoglycemic individuals is associated with greater probability of hypertension, abnormalities of glucose tolerance and proteinuria, and assessment of RFFRMD might, therefore, help stratifying cardiometabolic risk among normogly diabetic individuals with overweight/OBesity.
Abstract: Background and aim Sarcopenia is a condition mainly due to loss of fat-free mass (FFM) in elderly individuals. RFFMD, however, is also frequent in obese subjects due to abnormal body composition. Objective of this study was to evaluate the impact of relative fat-free mass deficiency (RFFMD) on cardiometabolic (CM) risk in obese normoglycemic individuals. Methods and results Overweight/obese American Indians from the Strong Heart Study population, without diabetes and with FBG ≤110 mg/dL and with GFR >60 mg/mL/1.73 m 2 were selected for this analysis ( n = 742). RFFMD was defined on the basis of a multivariable equation previously reported. Fasting glucose and 2 h-OGTT were measured together with urine albumin/creatinine excretion, laboratory and anthropometric parameters. In addition to lower FFM and greater adipose mass, participants with RFFMD had higher body mass index, waist circumference, C-reactive protein, fibrinogen, insulin resistance and urinary albumin/creatinine than participants with normal FFM (all p p p p Conclusions RFFMD in overweight/obese normoglycemic individuals is associated with greater probability of hypertension, abnormalities of glucose tolerance and proteinuria. Assessment of RFFRMD might, therefore, help stratifying cardiometabolic risk among normoglycemic individuals with overweight/obesity.
National Institutes of Health1, Harvard University2, University of Pittsburgh3, California Pacific Medical Center4, University of Balamand5, Imperial College London6, Northwestern University7, Memorial Hospital of South Bend8, Ohio State University9, Stanford University10, University of California, Davis11, Brown University12, University of California, Los Angeles13
TL;DR: In this large sample of postmenopausal women, age, exogenous estrogen use, physical activity, regular coffee intake, and BMI were significant correlates of SHBG concentrations, presenting potential targets for interventions.
Abstract: BACKGROUND: Circulating concentrations of sex hormone–binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood.
METHODS: We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study- and ethnicity-specific associations of age, reproductive history, usage of exogenous estrogen, body mass index (BMI), and lifestyle factors such as physical activity, smoking, alcohol consumption, coffee intake, and dietary factors with SHBG concentrations. These estimates were pooled using random-effects models. We also examined potential nonlinear associations using spline analyses.
RESULTS: There was no significant ethnic difference in the age-adjusted mean concentrations of SHBG. Age, exogenous estrogen use, physical activity, and regular coffee intake were positively associated with SHBG concentrations, whereas BMI was inversely associated with SHBG concentrations after adjustment for potential confounding factors. Similar patterns were observed among both ever users and never users of exogenous estrogen. The spline analysis indicated nonlinear relations of regular intake of coffee, age, and BMI with SHBG concentrations. Two or more cups/day of regular coffee consumption and age of 60 years or older were associated with higher SHBG concentrations; the inverse BMI–SHBG relation was especially strong among women whose BMI was below 30.
CONCLUSIONS: In this large sample of postmenopausal women, age, exogenous estrogen use, physical activity, regular coffee intake, and BMI were significant correlates of SHBG concentrations, presenting potential targets for interventions.
20 Oct 2014
TL;DR: This work investigated the associations of low-moderate arsenic exposure and arsenic metabolism with diabetes in patients with type 2 diabetes in the Netherlands and found no clear link between exposure and diabetes.
Abstract: Background: Little is known about the association between arsenic metabolism and diabetes. We investigated the associations of low-moderate arsenic exposure and arsenic metabolism with diabetes in ...
Journal Article•
TL;DR: This first study to interrogate the human metabolome of telomeric aging in American Indians provides initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.
Abstract: Background: Telomere length is an emerging biomarker for cellular senescence or biological aging. Short leukocyte telomere length (LTL) has been associated with a wide range of age-related metabolic disorders such as diabetes and cardiovascular disease. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolic profiles of biological aging assessed by telomere length in human. Objective: To identify metabolic profiles of leukocyte telomere length in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003). Methods: This study included 432 SHFS participants free of cardiovascular disease and type 2 diabetes. LTL was measured by quantitative polymerase chain reaction (qPCR). Plasma metabolites were detected using an untargeted metabolomics approach by high-resolution liquid chromatography-mass spectrometry (LC/MS). The association of leukocyte telomere length with concentration of each metabolite was examined using generalized estimating equation (GEE), adjusting for age, sex, study center, body mass index, fasting glucose and fasting insulin. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: After adjusting for covariates and multiple testing, three metabolites including cytosine, selenophosphate and pentyl propanoate, were significantly associated with LTL. Of these, cytosine was positively associated with LTL (β=0.0476, 95% CI, 0.0474 to 0.0478, P=1.90х10-7), and selenophosphate (β =-0.1522, 95% CI, -0.1525 to -0.1519, P=2.48х10-8) and pentyl propanoate (β =-0.0644, 95% CI, -0.0683 to -0.0606, P=1.08х10-8) were negatively associated with LTL. Multivariate analysis demonstrated that participants with longer (top telomere tertile) and shorter (bottom telomere tertile) LTL can be clearly separated by partial least square discriminant analysis (PLS-DA) using these three metabolites. Multiple unknown compounds were also independently associated with LTL. Conclusions: This study, for the first time, identifies metabolites and metabolic profiles associated with interindividual variability in leukocyte telomere length, independent of potential confounders. Our findings provide novel insights into understanding of telomere biology and metabolic mechanisms underlying age-related disorders.
TL;DR: In this paper, the authors examined the relationship between self-reported birth weight and the adult occurrence of type 2 diabetes mellitus in a large multi-ethnic population of women and found that lower birth weight was associated with increased T2D risk in American White and Black postmenopausal women.
TL;DR: It is demonstrated that multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se.
Abstract: Cigarette smoke is a strong risk factor for obesity and cardiovascular disease The effect of genetic variants involved in nicotine metabolism on obesity or body composition has not been well studied Though many genetic variants have previously been associated with adiposity or body fat distribution, a single variant usually confers a minimal individual risk The goal of this study is to evaluate the joint association of multiple variants involved in cigarette smoke or nicotine dependence with obesity-related phenotypes in American Indians To achieve this goal, we genotyped 61 tagSNPs in seven genes encoding nicotine acetylcholine receptors (nAChRs) in 3,665 American Indians participating in the Strong Heart Family Study Single SNP association with obesity-related traits was tested using family-based association, adjusting for traditional risk factors including smoking Joint association of all SNPs in the seven nAChRs genes were examined by gene-family analysis based on weighted truncated product method (TPM) Multiple testing was controlled by false discovery rate (FDR) Results demonstrate that multiple SNPs showed weak individual association with one or more measures of obesity, but none survived correction for multiple testing However, gene-family analysis revealed significant associations with waist circumference (p = 00001) and waist-to-hip ratio (p = 00001), but not body mass index (p = 020) and percent body fat (p = 029), indicating that genetic variants are jointly associated with abdominal, but not general, obesity among American Indians The observed combined genetic effect is independent of cigarette smoking per se In conclusion, multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se
TL;DR: Lower rates for coronary heart disease death but high rates of stroke mortality are found in western Alaska Native people; concordance between the 2 methods is better for cancer mortality.
Abstract: Objectives. We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths. Methods. Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and κ statistics. Results. Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than wo...
01 Jan 2014
TL;DR: Dietary intake of polyunsaturated fatty acids significantly modifies the effect of a leukotriene haplotype on carotid artery hypertrophy but not atherosclerosis in American Indians, independent of established cardiovascular risk factors.
TL;DR: A population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality.
Abstract: The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p
01 Jan 2014
TL;DR: Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians, independent of traditional risk factors including cigarette smoking per se.
Abstract: Background Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial. Methods Using a gene-family approach, we investigated the joint association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney function in 3620 American Indians participating in the Strong Heart Family Study, independent of known risk factors. Kidney function was evaluated by estimated glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and chronic kidney disease. The joint impact of smoking-related variants was assessed using the weighted truncated product method. Results Multiple SNPs showed marginal individual effect on renal function variability, and only a few survive multiple comparison correction. In contrast, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant associations of the nAChR gene family with kidney function variables including estimated glomerular filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps ≤ 0.0001) after adjusting for established risk factors including cigarette smoking. Conclusion Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians. The effects of these genetic variants on kidney function or damage are independent of traditional risk factors including cigarette smoking per se.