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Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women's Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90-1.11) in whites, 0.95 (0.85-1.06) in blacks, 0.96 (0.79-1.17) in Hispanics, and 0.88 (0.70-1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggested that n-6 fatty acids, especially linoleic acid (LA), have beneficial effects on CHD, whereas some in vitro studies have suggested that n-6 fatty acids, specifically arachidonic acid (AA), may have harmful effects. We examined the association of serum n-6 fatty acids with plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional study recruited 926 randomly selected men aged 40–49 years without CVD during 2002–2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI-1 was analysed in free form, both active and latent. Serum fatty acids were measured with gas-capillary liquid chromatography. To examine the association between total n-6 fatty acids (including LA and AA) and PAI-1, multivariate regression models were used. After adjusting for confounders, total n-6 fatty acids, LA and AA, were inversely and significantly associated with PAI-1 levels. These associations were consistent across three populations. Among 915 middle-aged men, serum n-6 fatty acids had significant inverse associations with PAI-1. [ABSTRACT FROM PUBLISHER]

The article discusses a study on the overall effect of statin medication use on incident diabetes mellitus (DM) risk including an analysis of women with and without self-reported cardiovascular disease (CVD). Participants included 161,808 postmenopausal women aged 50 to 79 years old. It suggests that statin use conveys an increased risk of new-onset DM in postmenopausal women and that statin-induced DM is a medication class effect not related to individual statin.

In randomized trials, the effect of vitamin D supplementation on blood pressure has been equivocal, while most prospective cohort studies have shown that the risk of incident hypertension is lower in people with higher levels of 25-hydroxyvitamin D (25(OH)D). The authors examined the association between levels of 25(OH)D and changes in blood pressure and incident hypertension in 4,863 postmenopausal women recruited into the Women’s Health Initiative between 1993 and 1998. Over 7 years, there were no significant differences in the adjusted mean change in systolic or diastolic blood pressure by quartile of 25(OH)D. The covariate-adjusted risk of incident hypertension was slightly lower in the upper 3 quartiles of 25(OH)D compared with the lowest quartile, but this was statistically significant only in the third quartile (hazard ratio = 0.67, 95% confidence interval: 0.46, 0.96). There was no significant linear or nonlinear trend in the risk of incident hypertension by untransformed or log-transformed continuous values of 25(OH)D. In postmenopausal women in this study, serum levels of 25(OH)D were not related to changes in blood pressure, and evidence for an association with lower risk of incident hypertension was weak. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Prospective epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited. OBJECTIVE: This study aimed to determine whether 25-hydroxyvitamin D [25(OH)D] concentrations were prospectively and independently associated with cardiovascular disease (CVD), cancer, and all-cause mortality in postmenopausal women. DESIGN: A substudy in 2429 postmenopausal women within the Women's Health Initiative (WHI) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD, cancer, and all-cause mortality. Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations, with adjustment for potential confounders. Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality. RESULTS: Of the 2429 women, 224 deaths occurred, with 79 deaths from CVD and 62 deaths from cancer. Multivariate-adjusted HRs that compared quartiles 1 (lowest) to 4 (highest) of 25(OH)D for all-cause mortality (HR: 1.25; 95% CI: 0.80, 1.95), CVD mortality (HR: 1.27; 95% CI: 0.81, 1.99), and cancer mortality (HR: 1.39; 95% CI: 0.88, 2.19) were not significant. There was a potential interaction (P = 0.08) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations (HR: 1.85; 95% CI: 1.00, 3.44) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity (HR: 0.96; 95% CI: 0.52, 1.76). CONCLUSION: Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health. This trial was registered at clinicaltrials.gov as NCT 00000611. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency that diabetes is reported on death certificates of decedents with known diabetes and describe trends in reporting over 8 years.Research Design and Methods: Data were obtained from 11,927 participants with diabetes who were enrolled in Translating Research into Action for Diabetes, a multicenter prospective observational study of diabetes care in managed care. Data on decedents (N=2,261) were obtained from the National Death Index from 1 January 2000 through 31 December 2007. The primary dependent variables were the presence of the ICD-10 codes for diabetes listed anywhere on the death certificate or as the underlying cause of death.Results: Diabetes was recorded on 41% of death certificates and as the underlying cause of death for 13% of decedents with diabetes. Diabetes was significantly more likely to be reported on the death certificate of decedents dying of cardiovascular disease than all other causes. There was a statistically significant trend of increased reporting of diabetes as the underlying cause of death over time (P<0.001), which persisted after controlling for duration of diabetes at death. The increase in reporting of diabetes as the underlying cause of death was associated with a decrease in the reporting of cardiovascular disease as the underlying cause of death (P<0.001).Conclusions: Death certificates continue to underestimate the prevalence of diabetes among decedents. The increase in reporting of diabetes as the underlying cause of death over the past 8 years will likely impact estimates of the burden of diabetes in the U.S. [ABSTRACT FROM AUTHOR]

Background: Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] may be associated with cardiometabolic disorders; however, little is known about their relation to intermediate metabolic and lipid markers. Objective: We investigated the relation of serum 25(OH)D concentrations to fasting insulin, glucose, dyslipidemia, adiposity, and prevalent metabolic syndrome. Design: We conducted this cross-sectional analysis in 292 postmenopausal women aged 50-79 y in the Women’s Health Initiative Calcium—Vitamin D (WI-IL-CaD) trial. Data were collected from 3 nested case-control studies that measured baseline serum 25(OH)D concentrations. Inverse probability weighting was used to approximate parameter estimates for the WFII-CaD population. Results: In weighted linear regression models adjusted for age, race- ethnicity, month of blood draw, region, case-control status, smoking, alcohol, physical activity, and history of cardiometabolic risk factors, there was an inverse association of serum 25(OH)D with adiposity [body mass index (BMI): β = -1.12 ± 0.30, P = 0.0002; waist circumference: β= -3.57 ± 0.49, P <0.0001; waist-hip ratio: β= -0.01 ± 0.002, P < 0.0001, triglycerides (β =-0.10 ± 0.02, P< 0.0001), and triglyceride:HDL-cholesterol ratio (β = -0.11 ± 0.03, P = 0.0003). The multivariable-adjusted odds ratio for metabolic syndrome for the highest (>52 nmolJL) compared with the lowest (<35 nmol/L) tertile of serum 25(OH)D concentrations was 0.28 (95% CI: 0.14, 0.56). Significant associations remained after adjustment for BMI. We observed no significant associations with LDL cholesterol, I-IDL cholesterol, insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), or homeostatic model assessment of β cell function (HOMA-β). Conclusion: Higher serum 25(OH)D concentrations may be inversely associated with adiposity, triglycerides, triglyceride:HDL-cholesterol ratio, and metabolic syndrome but are not associated with LDL and FIDL cholesterol, insulin, glucose, HOMA-IR, or HOMA-β in post- menopausal women. [ABSTRACT FROM AUTHOR]

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5x10-8 ). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large interchromosomal duplications can result in false positive associations in GWAS. [ABSTRACT FROM AUTHOR]

Background: Patients who speak Spanish and/or have low socioeconomic status are at greater risk of suboptimal glycemic control. Inadequate intensification of anti-glycemic medications may partially explain this disparity.Objective: To examine the associations between primary language, income, and medication intensification.Design: Cohort study with 18-month follow-up.Participants: One thousand nine hundred and thirty-nine patients with Type 2 diabetes who were not using insulin enrolled in the Translating Research into Action for Diabetes Study (TRIAD), a study of diabetes care in managed care.Measurements: Using administrative pharmacy data, we compared the odds of medication intensification for patients with baseline A1c ≥ 8%, by primary language and annual income. Covariates included age, sex, race/ethnicity, education, Charlson score, diabetes duration, baseline A1c, type of diabetes treatment, and health plan.Results: Overall, 42.4% of patients were taking intensified regimens at the time of follow-up. We found no difference in the odds of intensification for English speakers versus Spanish speakers. However, compared to patients with incomes <$15,000, patients with incomes of $15,000-$39,999 (OR 1.43, 1.07-1.92), $40,000-$74,999 (OR 1.62, 1.16-2.26) or >$75,000 (OR 2.22, 1.53-3.24) had increased odds of intensification. This latter pattern did not differ statistically by race.Conclusions: Low-income patients were less likely to receive medication intensification compared to higher-income patients, but primary language (Spanish vs. English) was not associated with differences in intensification in a managed care setting. Future studies are needed to explain the reduced rate of intensification among low income patients in managed care. [ABSTRACT FROM AUTHOR]

The article examines health outcomes linked with the Women's Health Initiative (WHI) Estrogen-Alone Trial, a randomized controlled trial that evaluated the effects of conjugated equine estrogens (CEE) among postmenopausal women with prior hysterectomy in the U.S. The WHI trial was terminated one year early due to a higher risk of stroke and low possibility for the planned date of termination to change the balance between risks and benefits. The authors found that coronary heart disease (CHD) and invasive breast cancer were the primary outcomes. They also found that CEE use for a median of 5.9 years was not linked with higher or lower risk of CHD, stroke and hip fracture, among others. They tackle the need to consider age and hysterectomy status when counseling women about hormone therapy.

Background. Examine the independent and joint effects of geriatric syndromes (GS) and cardiometabolic diseases (CMDs) on functional impairment. Methods. Cross-sectional analysis of baseline data from the Women's Health Initiative, including 62,829 women aged 65 years or older. GS (urinary incontinence, falls, and depression measured by the shortened Center for Epidemiological Studies-Depression scale/Diagnostic Interview Schedule screening instrument) and CMD (coronary artery disease, coronary heart failure, and diabetes) were self-reported. Physical and social functioning and general health subscales of the Short Form-36 dichotomized at the median for the study sample were used to assess functional impairment. Additive interaction between burden of GS and CMD was assessed using logistic regression models. Results. Forty-three percent of women had at least one GS; 14.1% had at least one CMD; and 6.9% had at least one of each. Compared with women with no GS or CMD, women with one or more GS but no CMD were as likely to have physical functioning impairments (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.73, 1.86) as those with CMD alone (OR = 1.97; CI = 1.84, 2.10). The association with social functioning was stronger for GS alone (OR = 2.10; CI = 2.02, 2.18) compared with CMD (OR = 1.60; CI = 1.50, 1.71). The association with general health was stronger for CMD alone (OR = 2.15; CI = 2.01, 2.29) compared with GS (OR = 1.68; CI = 1.62, 1.74). Significant interactions between GS and CMD were observed for all functional measures with 20%–30% of observed ORs attributable to additive interaction. Conclusion. GSs alone are associated with functional impairment in older women; the association is stronger in the presence of even one CMD. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS--A post hoc analysis of three nested casecontrol studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women's Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50-<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors. RESULTS--Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial. CONCLUSIONS--Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Current data suggest that low density lipoprotein (LDL) and high density lipoprotein (HDL) subclass concentrations relate directly to the risk of coronary heart disease (CHD). Earlier Studies indicated that Japanese in Japan had lower rates of CHD than Japanese Americans in Hawaii. Rates of CHD appear to continue to be lower in Japan despite increasing cholesterol levels in Japan and decreasing CHD rates in the United States. Objective: To provide insight into CHD rate differences. Methods: Nuclear Magnetic Resonance (NMR) measurements of lipoprotein subclasses were used to assess lipoprotein particle concentration and size in samples from these two genetically similar populations in Japan and Hawaii. Results: Japanese Americans had significantly higher age- and risk factor- adjusted concentrations of lipoprotein particles implicated in atherogenesis, including large very low density lipoprotein (VLDL; P < 0.001), small LDL (P < 0.001), and small HDL (women, P < 0.001; men, P < 0.01), and significantly lower concentrations of large LDL (P < 0.001) and the putative cardio-protective large HDL (P < 0.05) than Japanese in Japan. Average age- and risk factor- adjusted LDL and HDL particle sizes were also significantly (P < 0.001) smaller in Japanese Americans. Adjustment for body mass index markedly reduced the differences in some lipoprotein measures, including total LDL and large HDL particle concentrations for both genders, total VLDL particle concentration for women, and large VLDL concentration and average HDL particle size for men. Conclusions: Differences in lipoprotein subclass distributions and lifestyle factors such as body weight may contribute to differences in CHD incidence for Japanese in Japan and Japanese Americans. [ABSTRACT FROM AUTHOR]

Abstract: Both sagittal abdominal diameter (SAD) and waist circumference (WC) highly correlate with visceral adipose tissue (VAT) being linked to an atherogenic lipoprotein profile. However, it is uncertain whether SAD is a better correlate of atherogenic lipoprotein subfractions than WC. We examined relative associations of SAD vs WC with lipoprotein subfractions for US white and Japanese men, concurrently examining the associations of VAT vs subcutaneous adipose tissue with lipoprotein subfractions. A population-based sample of 260 white and 282 Japanese men aged 40 to 49 years was examined for VAT and subcutaneous adipose tissue by computed tomography; SAD and WC by a portable sliding-beam caliper and a measuring tape, respectively; and lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Both SAD and WC were significantly and positively associated with large very low-density lipoprotein and total and small low-density lipoprotein particle concentrations, and inversely associated with large high-density lipoprotein particle concentration for both white and Japanese men. In body mass index–adjusted regression models, the significant associations of SAD remained for both white and Japanese men, whereas those of WC became nonsignificant for white men. When SAD and WC were simultaneously included into the body mass index–adjusted models, the associations of SAD remained significant and statistically stronger than those of WC for both white and Japanese men. Furthermore, the pattern of the associations of SAD with those lipoprotein subfractions was comparable to that of the associations of VAT. Sagittal abdominal diameter was comparable to VAT and stronger than WC in the associations with atherogenic lipoprotein subfractions for middle-aged, nondiabetic, white and Japanese men. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the association between protein intake and incident frailty. DESIGN: Prospective cohort study. SETTING: Subset of the Women's Health Initiative Observational Study conducted at 40 clinical centers. PARTICIPANTS: Twenty-four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self-reported energy intakes (600–5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ). MEASUREMENTS: Baseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen). After 3 years of follow-up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand-36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake. RESULTS: Of the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8–16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23–50%) lower risk of frailty. CONCLUSION: Higher protein consumption, as a fraction of energy, is associated with a strong, independent, dose-responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention. [ABSTRACT FROM AUTHOR]

The article discusses the result of a study which investigated the association between antiepileptic drug (AED) use and falls, fractures, and bone mineral density (BMD) in postmenopausal women using data from the Women's Health Initiative (WHI). It was found that AED use increases the risk for site-specific and total fractures but is not associated with changes in BMD. The study notes that women at risk should pay attention to fall prevention.

TCF7L2 genetic variants were associated with progression to type 2 diabetes in Europeans. However, the role of TCF7L2 in type 2 diabetes remained uncertain in Chinese. Seventeen tag single nucleotide polymorphisms were genotyped in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. At baseline, the rs7903146 T allele in the exon 4 linkage disequilibrium (LD) block were associated with lower insulinogenic index at 60 min ( P = 0.01), while the rs290481 G allele near the 3′ end was associated with higher 2-h post-challenge glucose ( P = 0.003) and insulin concentration ( P = 0.02), elevated systolic ( P = 0.01) and diastolic blood pressure ( P = 0.006), lower waist circumference ( P = 0.01), and increased steady-state plasma glucose (SSPG) concentration measured with modified insulin suppression test ( P = 0.02). Over an average follow-up period of 5.43 years, participants with the rs7903146 T allele or variants in the same LD block, but not those with the rs290481 G allele, were more likely to progress to diabetes (hazard ratio = 2.61, 95% confidence interval, 1.27–5.39, P = 0.009) than were non-carriers. TCF7L2 gene expression was inversely associated with SSPG in human visceral ( r = −0.73, P = 0.006) and subcutaneous adipose tissue ( r = −0.62, P = 0.03). TCF7L2 may exert pleiotropic effects on insulin secretion or insulin resistance. However, only variants associated with impaired β-cell function predict progression to diabetes in Chinese. [ABSTRACT FROM AUTHOR]

The article presents a study on the role of antidepressant use in cardiovascular morbidity and mortality among postmenopausal women. The study compares the characteristics of postmenopausal women in the Women's Health Initiative (WHI) who are taking the antidepressants to those who are not. The results show that the antidepressant use is not linked with coronary heart disease (CHD) but selective serotonin reuptake inhibitor (SSRI) is connected with all-cause mortality and stroke risks.

Abstract: Among Asians, including Japanese, obesity is related to dyslipidemia and insulin resistance at a lower level of body mass index (BMI) compared with non-Hispanic whites (NHW). We hypothesize that this ethnic difference in the relationship between BMI and metabolic risks is partly associated with the ethnic difference in fat distribution, namely, liver fat as well as visceral adipose tissue. To compare liver fat content among Japanese vs NHW men, regional computed tomographic images were taken to measure liver computed tomographic density in population-based samples of 313 Japanese and 288 NHW men aged 40 to 49 years, along with the assessment of metabolic parameters. Liver fat content was higher in Japanese than NHW men (liver to spleen attenuation ratio [lower value means higher liver fat content]: 1.01 ± 0.16 vs 1.07 ± 0.15, respectively; P < .01), despite a lower mean BMI in Japanese men (BMI: 23.6 ± 2.9 vs 27.8 ± 4.2 kg/m2, P < .01). Moreover, Japanese men had a greater disposition for fatty liver with a small increase in BMI than NHW (P < .01), whereas both groups had a similar relationship between visceral adipose tissue and BMI. In both groups, liver fat content correlated with triglycerides, homeostasis model assessment of insulin resistance, and C-reactive protein. Liver fat content is higher among Japanese than NHW; and this ethnic difference becomes more robust with a small increase in BMI, suggesting that fatty liver is a sensitive marker for the failure of the adipose tissue to expand to accommodate an increased energy influx, and is associated with similar metabolic risk in Japanese despite lower BMI compared with NHW men. [Copyright &y& Elsevier]

Background: Arthritis is the most common chronic disease in the elderly. Studies show that rheumatoid arthritis is a risk factor for cardiovascular morbidity and mortality, and osteoarthritis is associated with an unfavorable cardiovascular risk factor profile. Methods: A/the Honolulu Heart Program's fourth examination in 1991 to 1993, arthritis smuts was assessed among a cohort of 3741 Japanese-American males, ages 71 to 93 years. Arthritis was determined by self-report of physician diagnosis, and subjects were divided into two groups: current arthritis and no current arthritis. Eight years of follow-up data are available for incident coronary heart disease (CHD) in 2777 subjects free of CHD at baseline. Age-adjusted rates of incident CHD and means of cardiovascular risk factors were compared in each group, Cox proportional hazards models were used to calculate relative risks, adjusting for common cardiovascular risk factors, alcohol, and use of aspirin or NSAIDs, or both. Results: There were 279 cases of incident CHD in the cohort over 8 years: in those with arthritis, 11.7% developed incident CHD. compared to 9.8% in those without arthritis (p = 0.24). Age-adjusted rates of incident CHD in those with and without arthritis were 20.5 and 18.0 per 1000 person-years, respectively (p = 0.25), Arthritis was not significantly associated with CHD risk factors. Arthritis was not a significant independent predictor of incident CHD (relative risk. 1.06; 95% CI. 0.74 to 1.51). Conclusions: Arthritis, and most probably osteoarthritis, may not be associated with most CHD risk factors or 8-year incident CHD hi elderly Japanese-American males. [ABSTRACT FROM AUTHOR]

Background. High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP). Methods. Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD4420 and Int 14A). Results. HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p = .002) but not related to non-CVD (p = .147) or total (p = .547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Tnt 14A variant. These men also had higher HDL-C levels (p = .047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p = .005). Conclusions. Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging. [ABSTRACT FROM AUTHOR]

Objective To assess the association between potential risk factors and subsequent clinically important abdominal aortic aneurysm events (repairs and ruptures) in women. Design Large prospective observational cohort study with mean follow-up of 7.8 years. Setting 40 clinical centres across the United States. Participants 161 808 postmenopausal women aged 50-79 enrolled in the women's health initiative. Main outcome measures Association of self reported or measured baseline variables with confirmed abdominal aortic aneurysm events assessed with multiple logistic regression. Results Events occurred in 184 women and were strongly associated with age and smoking. Ever smoking, current smoking, and amount smoked all contributed independent risk. Diabetes showed a negative association (odds ratio 0.29, 95% confidence interval 0.13, 0.68), as did postmenopausal hormone therapy. Positive associations were also seen for height, hypertension, cholesterol lowering treatment, and coronary and peripheral artery disease. Conclusions Our findings confirm the strong positive associations of clinically important abdominal aortic aneurysm with age and smoking in women and the negative association with diabetes previously reported in men. [ABSTRACT FROM AUTHOR]

Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to 115 signaling, we chose a large, homogeneous. long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function. despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the association between chronic kidney disease and incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass. DESIGN: Case-control study nested within a prospective study. SETTING: The Women's Health Initiative Observational Study conducted at 40 U.S. clinical centers. PARTICIPANTS: From 93,676 women aged 50 to 79 followed for an average of 7 years, 397 incident hip fracture cases and 397 matched controls were studied. MEASUREMENTS: Cystatin-C levels were measured on baseline serum using a particle-enhanced immunonepholometric assay. Estimated glomerular filtration rates (eGFRcys-c) were calculated using a validated equation and categorized into three groups (≥90.0 mL/min per 1.73 m2, 60.0–89.9 mL/min per 1.73 m2, and <60.0 mL/min per 1.73 m2 indicating chronic kidney disease Stages 3 to 4). RESULTS: The odds ratio (OR) for hip fracture was 2.50 (95% confidence interval (CI)=1.32–4.72) for eGFRcys-c less than 60 mL/min per 1.73 m2 compared with Stages 0 to 1, after adjustment for body mass, parental hip fracture, smoking, alcohol consumption, and physical function. No association was observed for eGFRcys-c of 60 to 90 mL/min per 1.73 m2 (OR=1.04, 95% CI=0.66–1.64). Additional adjustment for poor health status, hemoglobin, serum 25-hydroxy vitamin D, and bone metabolism markers did not affect these associations. Adjustment for plasma homocysteine reduced the OR for eGFRcys-c less than 60 mL/min per 1.73 m2 to 1.83 (95% CI=0.93–3.61). CONCLUSION: Women with eGFRcys-c levels less than 60 mL/min per 1.73 m2 have a substantially greater risk of hip fracture. Effects of renal function on homocysteine levels may partially mediate, or accompany, this association. [ABSTRACT FROM AUTHOR]

Background. Inflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older. Methods. The authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline 01 = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty. Results. Among the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend = .02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events. Conclusions. Overall, incidence of frailty was similar in current statin users and nonusers. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Experimental and epidemiologic studies suggest that calcium and vitamin D may reduce the risk of developing diabetes. We examined the effect of calcium plus vitamin D supplementation on the incidence of drug-treated diabetes in postmenopausal women. RESEARCH DESIGN AND METHODS -- The Women's Health Initiative Calcium/ Vitamin D Trial randomly assigned postmenopausal women to receive 1,000 mg elemental calcium plus 400 IU of vitamin D3 daily, or placebo, in a double-blind fashion. Among 33,951 participants without self-reported diabetes at baseline, we ascertained by treatment assignment new diagnoses of diabetes treated with oral hypoglycemic agents or insulin. Effects of the intervention on fasting measurements of glucose, insulin, and insulin resistance were examined among a subset of participants. RESULTS -- Over a median follow-up time of 7 years, 2,291 women were newly diagnosed with diabetes. The hazard ratio for incident diabetes associated with calcium/vitamin D treatment was 1.01 (95% CI 0.94-1.10) based on intention to treat. This null result was robust in subgroup analyses, efficacy analyses accounting for nonadherence, and analyses examining change in laboratory measurements. CONCLUSIONS -- Calcium plus vitamin D3 supplementation did not reduce the risk of developing diabetes over 7 years of follow-up in this randomized placebo-controlled trial. Higher doses of vitamin D may be required to affect diabetes risk, and/or associations of calcium and vitamin D intake with improved glucose metabolism observed in nonrandomized studies may be the result of confounding or of other components of foods containing these nutrients. [ABSTRACT FROM AUTHOR]

BACKGROUND The association between plasma adiponectin level and blood pressure remains inconclusive. Because obese subjects may have different mechanisms to regulate blood pressure, we hypothesized that obesity may be an important modifier. In order to minimize confounding effects from unidentified factors, a family-based design was employed to explore the relationship. METHODS A total of 1,048 subjects from 478 Chinese or Japanese families with a mean age of 50.4 ± 9.0 years were included (the SAPPHIRe (Stanford-Asian Pacific Program in Hypertension and Insulin Resistance) cohort). Blood pressure was recorded automatically and the average of the last two out of three consecutive readings was used in the analysis. A subject with "hypertension" was defined as one with a systolic blood pressure (SBP) ≥140 mm Hg, or a diastolic blood pressure (DBP) ≥90 mm Hg, or who was already on medication for hypertension. Obesity was defined as having a body mass index (BMI) ≥25 kg/m2. The updated homeostasis model assessment was used for calculating the indices of insulin sensitivity (HOMA2 %S). Fasting plasma adiponectin was determined using radioimmunoassay. RESULTS Subjects with hypertension had significantly lower plasma adiponectin levels than those without hypertension (5.99 ± 3.64 μg/ml vs. 6.65 ± 3.86 μg/ml, P < 0.01). Plasma adiponectin level correlated negatively with hypertension after adjusting for age, sex, and HOMA2%S (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.90-0.98). In subjects without hypertension (n = 349), the plasma adiponectin level correlated negatively with SBP in those who were obese, after adjustment for age, sex, BMI, and HOMA2 %S (β = -0.58, P = 0.03). The association was not significant in those without obesity. CONCLUSIONS Plasma adiponectin level correlates negatively with hypertension. In subjects without hypertension, the relationship between plasma adiponectin level and SBP depends on the presence of obesity. [ABSTRACT FROM AUTHOR]

Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the relationship between coronary artery calcification (CAC) and mortality in a sample of elderly men. DESIGN: Prospective cohort study. SETTING: The Honolulu Heart Program. PARTICIPANTS: A population-based sample of 224 men aged 84 to 96 with good cognitive function. METHODS: From 2004 to 2005, subjects received physical examinations including CAC determinations. Participants were followed for up to 3 years for all-cause mortality. RESULTS: In the course of follow-up, there were 17 deaths (28.0/1,000 person-years). Risk of death rose consistently and significantly as CAC scores increased ( P=.001). For CAC scores less than 10, no deaths were observed. For scores of 10 or higher, risk of death rose from 13.2 per 1,000 person-years for CAC scores of 10 to 100 to 48.6 per 1,000 person-years for CAC scores greater than 1,000. Findings persisted after adjusting for age and traditional risk factors. In this sample of elderly men, CAC was the only factor with a significant relationship with total mortality. CONCLUSION: Higher CAC scores in elderly men are associated with greater risk of death. Screening for CAC could be important for developing strategies to improve longevity in elderly people, particularly at an age when associations between mortality and traditional risk factors are weak. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the relationship between low levels of human serum albumin (HSA) and the incidence of coronary heart disease (CHD) in a cohort of elderly Japanese-American men. Using data from the Honolulu Heart Program's fourth examination (1991-1993), HSA levels of 998 Japanese American men aged 71-93 years was compared with plasma levels of fibrinogen, total cholesterol HDL cholesterol, LDL cholesterol triglycerides, diastolic BP, BMI, and fasting blood glucose. HSA was significantly negatively associated with age and fibrinogen, and significantly positively associated with total cholesterol, HDL cholesterol LDL cholesterol triglycerides, diastolic BP, BMI and fasting blood glucose. After adjusting for age, tertiles of HSA were significantly positively associated with total cholesterol, HDL cholesterol and triglycerides, and significantly negatively associated with fibrinogen. Using multivariate stepwise regression, significant correlations were seen between HSA and fibrinogen, cholesterol age, HDL cholesterol and triglycerides, and a borderline correlation was seen with systolic blood pressure. However, the model R-square for all variables was only 0.10. In conclusion, HSA levels are significantly associated with several traditional cardiovascular risk factors, particularly serum lipid levels. [ABSTRACT FROM AUTHOR]

This study examined the effect of a 12-week non-instrumental resistance training program using body weight as a load (RT-BW) on body composition, fat distribution and metabolic profiles in elderly males and females. Healthy, non-diabetic, elderly volunteers (22 males and 30 females) aged 65–82 years were non-randomly divided into RT-BW (12 males and 20 females) and control (10 males and 10 females) groups. The RT-BW subjects were trained three times per week for 12 weeks according to a specified protocol involving a combination of upper and lower body weight and rubber tubing exercises. We evaluated body composition and fat distribution using anthropometry, dual energy X-ray absorptiometry and ultrasonography, and measured serum lipid levels and HbA1c at baseline and after 12 weeks of training. Changes over 12 weeks were significantly greater in the RT-BW group compared with the control group, with a decrease in waist circumference, pre-peritoneal (visceral) fat thickness and thigh fat thickness, and an increase in thigh muscle thickness. On the other hand, the changes in body weight, fat mass and fat free mass were no different between the groups . Further, there were significantly greater changes of metabolic profiles in the RT-BW group with an increase in HDL cholesterol and a decrease in triglyceride and HbA1c. There was a significant between-group difference in diastolic blood pressure. Relatively short-term, non-instrumental resistance training using body weight as a load was effective in improving fat distribution and metabolic profiles in healthy elderly people without weight loss. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a common disorder associated with obesity. Lower plasma levels of adiponectin were associated with type 2 diabetes. Candidate regions on chromosomes 1 (∼70 cM) and 14 (∼30 cM) were evaluated for replication of suggestive linkage results for type 2 diabetes/impaired glucose homeostasis in an independent sample of Japanese Americans. Replication of independent linkage evidence for serum levels of adiponectin on chromosome 14 was also evaluated. We investigated 529 subjects from 175 sibships who were originally part of the Honolulu Heart Program. Analyses included nonparametric linkage and association using SAGE (Statistical Analysis for Genetic Epidemiology) and FBAT (family-based test of association) programs and Monte Carlo simulation of Fisher's exact test in SAS. For type 2 diabetes/impaired glucose metabolism, nominal linkage evidence (P < 0.02) followed-up by genotypic association (P = 0.016) was found with marker D14S297 at 31.8 cM; linkage analyses using only diabetes phenotype were also nominally significant at this marker (P < 0.02). Nominal evidence for genotypic association to adiponectin serum level phenotype (P = 0.04) was found with the marker D14S1032 at 23.2 cM. The present study was limited by relatively small sample size. Nevertheless, these results corroborate earlier studies, suggesting that further research is warranted in the candidate region ∼30 cM on chromosome 14. Diabetes 56:537-540, 2007 [ABSTRACT FROM AUTHOR]

The article presents a medical research study on the midlife risk factors and healthy survival of men. The objective of the study was to find whether midlife biological, lifestyle, and sociodemographic risk factors are associated with survival and exceptional survival, which is defined as survival to a specified age without incidence of six major chronic diseases or impairment. According to the article, high grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with exceptional survival.

Background: The purpose of the study was to use factor analysis to investigate the contribution of a directly measured insulin sensitivity index, steady-state plasma glucose (SSPG) from insulin suppression test (IST), to a clustering of cardiovascular risk factors in hypertensive subjects. Methods: A total of 204 nondiabetic hypertensive patients who received IST for SSPG were included for current analysis. Factor analysis was performed to explore the contribution of SSPG as additional information to a clustering of risk factors in these subjects. Results: In factor analysis, SSPG aggregated with metabolic variables in an obesity–hyperinsulinemia domain that included two factors: one with positive loadings for SSPG, 2-h glucose, and Log 2-h insulin; and the other with positive loadings for body mass index, waist circumference, and fasting glucose. Fasting insulin linked the two factors together and explained 38.3% of the total variance. Systolic and diastolic blood pressures were loaded on a blood pressure domain separately. The third domain consisted of two factors: one with positive loadings for Log triglycerides and negative loading for high-density lipoprotein cholesterol; and the other with positive loadings for Log triglycerides and non–high-density lipoprotein cholesterol. The model loaded without SSPG explained a proportion of the total variance (78.5%) similar to that achieved with the model loaded with SSPG (77.1%). Conclusions: Directly measured insulin sensitivity index SSPG clustered with 2-h glucose and Log 2-h insulin in factor analysis in a cohort consisting entirely of hypertensive subjects. However, the contribution of SSPG as additional information to explain the total variance seems to be insignificant. [Copyright &y& Elsevier]

Atherosclerosis accounts for 75% of all deaths from cardiovascular disease and includes coronary heart disease (CHD), stroke, and other diseases of the arteries. More than half of all CHD is attributable to abnormalities in levels and metabolism of lipids. To locate genes that affect total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides, genome-wide linkage scans for quantitative trait loci were performed using variance components methods as implemented in SOLAR on a large diverse sample recruited as part of the Family Blood Pressure Program. Phenotype and genetic marker data were available for 9,299 subjects in 2,953 families for total cholesterol, 8,668 subjects in 2,736 families for HDL, and 7,760 subjects in 2,499 families for triglycerides. Mean lipid levels were adjusted for the effects of sex, age, age2, age-by-sex interaction, body mass index, smoking status, and field center. HDL-C and triglycerides were further adjusted for average total alcoholic drinks per week and estrogen use. Significant linkage was found for total cholesterol on chromosome 2 (LOD = 3.1 at 43 cM) in Hispanics and for HDL-C on chromosome 3 (LOD = 3.0 at 182 cM) and 12 (LOD = 3.5 at 124 cM) in Asians. In addition, there were 13 regions that showed suggestive linkage (LOD ≥ 2.0); 7 for total cholesterol, 4 for HDL, and 2 for triglycerides. The identification of these loci affecting lipid phenotypes and the apparent congruence with previous linkage results provides increased support that these regions contain genes influencing lipid levels. [ABSTRACT FROM AUTHOR]

Caloric (or dietary) restriction (CR) extends lifespan and lowers risk for age associated diseases in a phylogenetically diverse group of species. Whether prolonged CR increases average or maximum lifespan or promotes a more youthful physiology in humans at advanced ages is not yet known. However, available epidemiological evidence indicates that CR may already have contributed to an extension of average and maximum life span in one human population and appears to have lowered risk for age associated chronic diseases in other human populations. We review the human studies in the context of a special human population, older Okinawans, who appear to have undergone a mild form of prolonged CR for about half their adult lives. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To improve and broaden the applicability of performance-based measures of function for use in clinical and research settings. DESIGN: Cross-sectional repeated-measures study. SETTING: Research clinic. PARTICIPANTS: Population-based sample of Japanese Americans without significant functional impairments aged 35 to 55 and 56 to 71 (N=203). MEASUREMENTS: Performance-based measures of physical function, including range of standard tests, newer automated measures of balance and strength and data on cognitive function, lifestyle, medical history, and physical activity. RESULTS: Of the nonplatform balance measures, only the one-leg stand was reliable (reliability coefficient (rc) =0.69) and able to discriminate between functional levels. Combining the Fourth National Health and Nutrition Examination Survey protocol of folded arm position while standing on a foam pad with the more-sophisticated balance platform test had the highest reliability and discrimination. With the strength chair, high rcs (0.88–0.96) were found for upper and lower extremity tests. Timed chair stands, a test of lower extremity and central strength were reliable. The 6-minute walk had a high rc (0.90). CONCLUSION: Many performance tests used today are not reliable. Only a few discriminate between the most highly functioning individuals and individuals with good function. Thus, a new recommended battery includes unassisted single-leg stand, balance platform “foam pad, eyes closed,” elbow flexion and knee extension strength (strength chair), grip strength, timed chair stands, and the 6-minute walk. These simple performance-based tests have good reliability and discrimination across the range of function and can be used in most clinical and research settings to quickly assess global functional level. [ABSTRACT FROM AUTHOR]

The article assesses whether urine dipstick screening for protein predicted stroke and coronary heart disease (CHD) in the Honolulu Heart Program cohort in Hawaii. It was hypothesized that stroke will less likely develop proteinuria and that the condition has a closer relation with CHD. The research was determined through the use of the urine dipstick screening test. Proteinuria detected at urine dipstick screening independently predicted increased risk for incident stroke and incident CHD over 27 years in this cohort.

The article presents a study conducted by the Women's Health Initiative to determine the effects of the use of estrogen and estrogen combined with progestin, as a form of hormonal therapy among women who have no uterus. Study shows that the use of estrogen alone has less risk of developing venous thromboembolism than the use of estrogen with progestin.

Okinawa, an isolated island prefecture of Japan, has among the highest prevalence of exceptionally long-lived individuals in the world; therefore, we hypothesized that, within this population, genes that confer a familial survival advantage might have clustered. We analyzed the pedigrees of 348 centenarian families with 1142 siblings and compared sibling survival with that of the 1890 Okinawan general population cohort. Both male and female centenarian siblings experienced approximately half the mortality of their birth cohort--matched counterparts. This mortality advantage was sustained and did not diminish with age in contrast to many environmentally based mortality gradients, such as education and income. Cumulative survival advantages for this centenarian sibling cohort increased over the life span such that female centenarian siblings had a 2.58-fold likelihood, and male siblings a 5.43-fold likelihood, versus their birth cohorts, of reaching the age of 90 years. These data support a significant familial component to exceptional human longevity. [ABSTRACT FROM AUTHOR]