Alcohol use and cognitive aging in middle-aged men: The Vietnam Era Twin Study of Aging.

OBJECTIVE: To determine associations of alcohol use with cognitive aging among middle-aged men. METHOD: 1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003-2007 to 2016-2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1-4 drinks in past 14 days), light (5-14 drinks), moderate (15-28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors. RESULTS: Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by -0.21 SD (95% CI -0.35, -0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, -0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association. CONCLUSIONS: Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Dual impairments in visual and hearing acuity and age-related cognitive decline in older adults from the Rancho Bernardo Study of Healthy Aging.

BACKGROUND: We examined the associations between dual impairments in visual and hearing acuity and aging-related cognitive decline. METHODS: This was a longitudinal study of adults who had visual and hearing acuity and cognitive function assessed in 1992-1996 and were followed for up to 24 years (mean = 7.3 years), with up to five additional cognitive assessments. Visual impairment was defined as vision worse than 20/40, hearing impairment as pure-tone average thresholds >25 dB. Associations were tested using linear mixed-effects regressions. RESULTS: Of 1,383 participants, 293 had visual impairment, 990 had a hearing impairment and 251 had both deficits. In fully adjusted models, low visual acuity was associated with poorer Mini-Mental State Examination (MMSE; ß = -0.29) and Trail-Making Test Part B (Trails B; ß = 13.22) performance, and with faster declines in MMSE (ß = -0.12) and Trails B (ß = 1.84). The combination of low visual and low hearing acuity was associated with poorer MMSE (ß = -0.44) and Trails B (ß = 11.20) scores, and with faster declines in MMSE (ß = -0.19), Trails B (ß = 3.50), and Verbal Fluency Test (VFT; ß = -0.14) performance. Associations were similar in men and women. CONCLUSION: Impairments in both vision and hearing are associated with a more rapid decline in cognitive function with aging.

Association Between Depressive Symptoms and Incident Cardiovascular Diseases.

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, Setting, and Participants: A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposures: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. Results: Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Lifetime physical activity and late-life cognitive function: the Rancho Bernardo study.

BACKGROUND: physical activity in older age has been associated with better cognitive function, but the role of earlier life physical activity is less well understood. OBJECTIVE: determine associations between physical activity throughout the lifespan and cognitive function in older age. DESIGN: cross-sectional study. SETTING: the Rancho Bernardo Study of Healthy Aging in southern California. SUBJECTS: A total of 1,826 community-dwelling men and women (60-99 years) who attended a research visit in 1988-92. METHODS: participants underwent cognitive testing at older age, and reported physical activity as a teenager, at age 30 years, 50 years and currently. For each time-point, participants were classified as regularly active (3+ times/week) or inactive. RESULTS: regular physical activity was associated with better cognitive function, with physical activity at older ages showing the strongest associations. Physical activity in older age was associated with better global cognitive function, executive function and episodic memory, regardless of intensity. Intense physical activity in teenage years was associated with better late-life global cognitive function in women. Teenage physical activity interacted with older age physical activity on executive function; those active at both periods performed better than those active at only one period. Similar patterns of associations were observed after excluding individuals with poor health. CONCLUSIONS: regular physical activity in older age, regardless of intensity, is associated with better cognitive function. Physical activity in teenage years may enhance cognitive reserve to protect against age-related decline in executive function. Further research is needed to assess the effect of physical activity across the lifespan on healthy brain ageing.

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

OBJECTIVE: This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. DESIGN/SETTING/PARTICIPANTS: Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. MEASUREMENTS: Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. RESULTS: Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. CONCLUSIONS: Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort.

Associations of Abdominal Muscle Area with 4-Year Change in Coronary Artery Calcium Differ by Ethnicity Among Post-Menopausal Women.

OBJECTIVE: To examine the association of abdominal muscle area with coronary artery calcium (CAC) presence, extent, and progression in a multi-ethnic cohort of older, community-dwelling post-menopausal women. DESIGN AND SETTING: Cross-sectional and longitudinal population-based cohort. PARTICIPANTS: The sample comprised 179 non-Hispanic White women, 116 Filipina women and 144 African American women, all without known CVD, who underwent chest and abdominal computed tomography (CT) scans twice about four years apart for abdominal muscle and fat, as well as CAC. MAIN OUTCOME MEASURES: CAC presence, extent and progression. RESULTS: There was a significant interaction of ethnicity with baseline oblique muscle area (p-for-interaction .01), and marginally significant interactions with baseline total and paraspinal muscle for change in CAC (p-for-interactions both .09). Among Filipina women, each standard deviation (SD) greater total muscle area was associated with a 26% (95% CI (-43%, -4%), P=.02) reduced rate of change in CAC; higher paraspinal and oblique muscle area were associated with a 24% (-38%, -6%, P=.01) and a 37% (-53%, -16%, P=.0002) reduced rate of change in CAC, respectively. These associations were not significant in African American or non-Hispanic White women. There were no significant associations of abdominal muscle with CAC presence or extent, nor were there significant ethnicity by muscle interactions in these models. CONCLUSIONS: Among Filipina women, greater abdominal muscle mass is associated with a decreased rate of CAC progression. Higher muscle mass may be important for this group in reducing CVD outcomes.

Urine creatinine-based estimates of fat-free mass in community-dwelling older persons: the Rancho Bernardo study.

OBJECTIVES: To determine whether a previously developed and externally validated equation using common variables (demographics and weight) that are important determinants of muscle mass to estimate 24-hour urine creatinine excretion rate (eCER) is associated with muscle mass and whether spot urine creatinine (UCr) provides similar estimates of muscle mass. DESIGN: Observational cross-sectional cohort study. SETTING: The Rancho Bernardo Study, San Diego, California. SUBJECTS: A total of 1,371 Caucasian, middle class, community-dwelling older adults. INTERVENTION: Morning spot UCr and fat-free mass (FFM) by dual-energy x-ray absorptiometry were measured. eCER was calculated: eCER (mg/day) = 879.89 + 12.51 × weight (kilogram) - 6.19 × age + 34.51 if black - 379.42 if female. Pearson correlation coefficients and linear regression were used to determine strengths of association of eCER and spot UCr with FFM. RESULTS: Mean age was 70 years, and 58% were women. eCER was strongly correlated with FFM (r = 0.95, P < .001), a correlation that was superior to that of spot UCr (r = 0.40, P < .001). CONCLUSIONS: An equation incorporating age, weight, sex, and race to estimate eCER is highly correlated with FFM in community-dwelling older persons and provides a more precise estimate than spot UCr. A simple screening tool for sarcopenia in older persons may allow interventions to maintain or improve muscle mass. Future studies should evaluate whether eCER predicts sarcopenia-related frailty and mortality in older persons.

Galectin-3 is independently associated with cardiovascular mortality in community-dwelling older adults without known cardiovascular disease: The Rancho Bernardo Study.

BACKGROUND: Galectin-3 is a marker of myocardial fibrosis that has been implicated in the pathophysiologic pathway of fibrosis; its association with all-cause and cardiovascular disease (CVD) mortality in a community-based cohort free of baseline CVD has not been reported. Our aim was to determine the association between galectin-3 levels and all-cause and CVD mortality in community-dwelling older adults without known CVD. METHODS: We measured plasma galectin-3 levels in 1,393 Rancho Bernardo Study participants without CVD with a mean age of 70 years. Participants were followed up for a mean of 11 years for coronary heart disease, CVD mortality, and all-cause mortality. RESULTS: During follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and renal function, galectin-3 was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase 1.30, 95% CI 1.10-1.53) and all-cause mortality (HR 1.12, 1.01-1.24), but not coronary heart disease (HR 1.09, 0.92-1.30). After further adjusting for N-terminal pro B-type natriuretic peptide, galectin-3 remained an independent predictor (HR 1.24, 1.05-1.47) of CVD mortality. Galectin-3 improved the c statistic (0.847-0.851, P = .003) for prediction of CVD death. Net reclassification improvement (>0) with the addition of galectin-3 was 35% (P < .0001); the integrated discrimination index was also significant (P = .03). Participants with both galectin-3 and N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 of these markers (HR 1.74, 1.24-2.43). CONCLUSION: Higher levels of galectin-3 are independently associated with all-cause and CVD mortality among community-dwelling older adults with no known CVD at baseline.

Fetuin-A, a new vascular biomarker of cognitive decline in older adults.

OBJECTIVES: Fetuin-A is an abundant plasma protein known to predict vascular disease. Fetuin-A levels are lower in patients with Alzheimer's disease in proportion to the severity of cognitive impairment, but their association with normal cognitive ageing is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in community-dwelling older adults. DESIGN/PATIENTS/MEASUREMENTS: A population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992-1996; 855 had repeat cognitive function assessment a median of 4 years later. RESULTS: Adjusting for age, sex, education and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE; P = 0·012) and a tendency for better Trails Making B scores (P = 0·066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P = 0·010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P = 0·005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P = 0·33). Fetuin-A was not related to Category Fluency performance. Results were independent of multiple vascular risk factors and comorbid conditions. CONCLUSIONS: Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with less likelihood of major decline in these cognitive abilities over a 4-year period. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline.

Relationships between serum and urine phosphorus with all-cause and cardiovascular mortality: the Osteoporotic Fractures in Men (MrOS) Study.

BACKGROUND: Serum phosphorus is associated with cardiovascular disease (CVD) in the general population, but may not comprehensively reflect phosphorus homeostasis. Whether urine phosphorus-creatinine ratio (a marker of intestinal absorption) or urine fractional excretion of phosphorus (FEPi; a marker of urinary phosphorus handling) is associated with risk of mortality or CVD is uncertain. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 1,325 community-dwelling men 65 years or older participating in the MrOS Study. PREDICTOR: Serum phosphorus, urine phosphorus-creatinine ratio, and FEPi. OUTCOMES: All-cause and CVD death. RESULTS: Mean age was 74 ± 6 (SD) years, estimated glomerular filtration rate was 75 ± 16 mL/min/1.73 m(2), and serum phosphorus level was 3.2 ± 0.4 mg/dL. During a median follow-up of 9.3 years, there were 364 (120 CVD) deaths. After adjustment for demographics, CVD risk factors, and kidney function, the risks of all-cause death in the highest quartiles of serum phosphorus (≥3.6 mg/dL), urine phosphorus-creatinine ratio (≥0.55), and FEPi (≥18%) were 1.63 (95% CI, 1.23-2.17), 1.22 (95% CI, 0.90-1.65), and 0.88 (95% CI, 0.64-1.23), respectively, compared to the lowest quartiles of each. Results were similar for CVD death. Results also were similar in those with estimated glomerular filtration rate ≥60 and <60 mL/min/1.73 m(2). LIMITATIONS: Older all-male cohort. Few had advanced chronic kidney disease. Spot urine specimens were used. CONCLUSIONS: In community-living older men, higher serum phosphorus concentrations are associated with all-cause and CVD death. In contrast, urine phosphorus-creatinine ratio and FEPi are not. These findings do not support using urine phosphorus-creatinine ratio or FEPi as adjuvant measures to predict risk of mortality or CVD in the general population.

Growth-differentiation factor-15 is a robust, independent predictor of 11-year mortality risk in community-dwelling older adults: the Rancho Bernardo Study.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic marker in patients with cardiovascular disease (CVD), but its prognostic value in community-dwelling adults has not been reported. We hypothesized that GDF-15 would add incremental power for prediction of mortality in a population of community-dwelling older adults without known heart disease. METHODS AND RESULTS: We measured plasma GDF-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein levels in 1391 Rancho Bernardo Study participants, mean age 70 years, with no history of CVD and followed them for a mean of 11 years. In models adjusted for traditional CVD risk factors, GDF-15 was a robust predictor of all-cause, cardiovascular, and noncardiovascular mortality. GDF-15 was a stronger predictor of all-cause mortality than either NT-proBNP or C-reactive protein (hazard ratio [95% confidence interval] per SD log(10) units 1.5 [1.3 to 1.8], P<0.0001 for GDF-15 versus 1.3 [1.2 to 1.5], P<0.0001 for NT-proBNP; C-reactive protein was not a significant predictor). Among biomarkers considered, only GDF-15 predicted noncardiovascular death (hazard ratio 1.6 [1.4 to 2.0], P<0.0001). Growth differentiation factor-15 improved discrimination and modestly but significantly improved reclassification for all-cause and noncardiovascular mortality with borderline improvement for cardiovascular mortality; NT-proBNP significantly improved reclassification for all-cause and for cardiovascular mortality; C-reactive protein did not improve reclassification for any end point tested. Participants in the highest quartile of both GDF-15 and NT-proBNP had an increased risk of death compared with participants with only NT-proBNP elevated (hazard ratio 1.5 [1.1 to 2.0], P=0.01). CONCLUSIONS: Growth differentiation factor-15 is a strong predictor of all-cause, cardiovascular, and noncardiovascular mortality in community-dwelling older individuals, adding incremental value to traditional risk factors and to NT-proBNP and C-reactive protein levels.

Extremes of an aromatase index predict increased 25-year risk of cardiovascular mortality in older women.

BACKGROUND: Peripheral conversion of androgens to oestrogens via aromatase is the primary source of oestrogen in postmenopausal women and may play a role in cardiovascular health. DESIGN: Prospective. PARTICIPANTS, MEASUREMENTS: The association of an index of aromatase activity (AROM), the serum oestrone-to-androstenedione ratio, with 25-year cardiovascular disease (CVD) mortality was examined in 819 postmenopausal non-oestrogen using women (mean age at baseline = 72). RESULTS: Overall, 247 deaths were attributed to CVD. The median AROM value was 60 (95% range 17-129). AROM was positively correlated with age (r = 0·28) and body mass index (BMI) (r = 0·22) (P < 0·001). The age-adjusted risk for CVD mortality was significantly elevated for women in the lowest (HR = 2·01, 95% CI 1·31-3·12) and highest (HR = 1·51, 95%CI 1·02-2·22) quintiles of AROM, compared with the middle quintile. This U-shaped association persisted after additional adjustment for BMI, waist-to-hip ratio, exercise, smoking, alcohol use and traditional CVD risk factor covariates. There was a significant interaction of AROM and BMI (P = 0·001), such that high AROM was associated with a 63% reduction in risk of CVD death for women with low BMI (<22 kg/m(2) ), but with 2·1- to 2·5-fold increased risk in women with mid-range (22-<25 kg/m(2) ) and high (≥25 kg/m(2) ) BMI. Oestradiol did not influence AROM associations and was not independently related to CVD death. CONCLUSIONS: These results suggest that aromatase is a novel endocrine factor predictive of CVD mortality among postmenopausal women. If confirmed, additional studies are needed to determine whether extremes of aromatase reflect genetic influences or underlying disease processes.

Moderate Alcohol Use Is Associated with Reduced Cardiovascular Risk in Middle-Aged Men Independent of Health, Behavior, Psychosocial, and Earlier Life Factors.

We examined whether the often-reported protective association of alcohol with cardiovascular disease (CVD) risk could arise from confounding. Our sample comprised 908 men (56−67 years), free of prevalent CVD. Participants were categorized into 6 groups: never drinkers, former drinkers, and very light (1−4 drinks in past 14 days), light (5−14 drinks), moderate (15−28 drinks), and at-risk (>28 drinks) drinkers. Generalized linear mixed effect models examined the associations of alcohol use with three established CVD risk scores: The Framingham Risk Score (FRS); the atherosclerotic CVD (ASCVD) risk score; and the Metabolic Syndrome (MetS) Severity score, adjusting for group differences in demographics, body size, and health-related behaviors. In separate models we additionally adjusted for several groups of potentially explanatory factors including socioeconomic status, social support, physical and mental health status, childhood factors, and prior history of alcohol misuse. Results showed lower CVD risk among light and moderate alcohol drinkers, relative to very light drinkers, for all CVD risk scores, independent of demographics, body size, and health-related behaviors. Alcohol-CVD risk associations were robust to further adjustment for several groups of potential explanatory factors. Study limitations include the all-male sample with limited racial and ethnic diversity, and the inability to adjust for sugar consumption and for patterns of alcohol consumption. Although this observational study does not address causation, results show that middle-aged men who consume alcohol in moderation have lower CVD risk and better cardiometabolic health than men who consume little or no alcohol, independent of a variety of health, behavioral, psychosocial, and earlier life factors.

Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum phosphorus, and urine phosphorus: the Heart and Soul Study.

BACKGROUND: Menopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown. STUDY DESIGN & SETTING: Cross-sectional study of ambulatory individuals with prevalent cardiovascular disease. PREDICTORS: Sex and, in women, use or nonuse of estrogen. OUTCOMES: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations. RESULTS: For 987 participants, mean age was 67 ± 11 years, 182 (18%) were women, and 46 (25%) were using estrogen. Mean estimated GFR was 71 ± 23 (SD) mL/min/1.73 m(2). Compared with women who were not using estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and 45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P < 0.001). LIMITATIONS: Most participants were men. Estrogen therapy was not randomly assigned. CONCLUSIONS: Older women who are not using estrogen have higher FGF-23 levels than either men or women using estrogen. In the context of prior literature, these data suggest that postmenopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause.

Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease.

OBJECTIVE: To investigate a possible link between cardiovascular risk factors and age-related cognitive decline, the association of the 1998 Framingham Cardiac Risk Score (FCRS) with the trajectory of cognitive function test (CFT) performance over an 18 year period was examined in adults 50 years and older without clinical heart disease at baseline. METHODS: Participants were 985 men and women who had assessments of cognitive function at 3- to 4-year intervals. The association of FCRS category with CFT score trajectory was examined using mixed-effects models stratified by sex and controlling for age, educational level, and number of successive cognitive assessments. RESULTS: At baseline, median FCRS corresponded to a 14% risk of a coronary heart disease event within 10 years for men and an 8% risk for women; 31% of men and 6% of women were at high (>20%) risk. In longitudinal analyses, women with FCRS risk higher than 7% had a higher rate of decline on tests of verbal fluency (p values < .05) and long-term recall (p values < .01) compared with low-risk women; modest, but significant (p values < .05), differences in the trajectory of Mini-Mental State Examination and Trail-Making Test B scores were also apparent. FCRS category was not related to the rate of decline in CFT performance in men. CONCLUSIONS: For older women, very low levels of risk of coronary heart disease were associated with preservation of cognitive function for 10 years, suggesting that the maintenance of cardiovascular health may slow cognitive decline. The minimal association in men, who were at higher baseline risk, may be due to the selective attrition of men with greater cognitive decline.

Dietary Potassium Intake and 20-Year All-Cause Mortality in Older Adults: The Rancho Bernardo Study.

We examined the association between dietary potassium intake and all-cause and cause-specific mortality among community-dwelling older adults. Potassium intake was assessed with a food frequency questionnaire administered to 1,363 older adults (mean age 71.0 ± 10.6 years). Cox proportional hazard regressions estimated hazard ratios for sex-specific quintiles of calorie-adjusted potassium in relation to all-cause and cause-specific (cardiovascular disease, CVD, and stroke) mortality, adjusting for numerous covariates. There were 855 deaths (63% mortality) during the 20-year follow-up. Relative to the third quintile, potassium intake in the lowest quintile only was associated with increased risk of all-cause mortality (fully-adjusted hazard ratio 1.33; 95% CI 1.06, 1.67). Potassium intake was not significantly associated with CVD or stroke mortality. These results suggest that low potassium intake is associated with increased risk of mortality independent of overall health status. Ensuring adequate potassium in the diet may be an important strategy for reducing risk of earlier mortality among older adults.