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Background: Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score.Methods: This prospective analysis included 3837 Whitehall II cohort participants screened in 2008 to 2009, and followed for 11.7 years (mean=10.3, SD=1.81), without history of stroke, myocardial infarction, or coronary heart disease.Results: Mean age of the sample was 65.0 years (SD=5.6), 2831 participants (73.8%) were male and mean atherosclerotic cardiovascular disease risk score was 13.8%. At the end of follow-up, 411 individuals (10.7%) had suffered a major cardiovascular event. Those in the highest aortic pulse wave velocity quartile were at high risk (hazard ratio, 2.99 [95% CI, 2.25-3.97]) and reached the threshold for statin medication (7.5% risk) after 5 years whereas others reached it after 10 years (difference P<0.001). The addition of aortic pulse wave velocity to the risk score improved the C statistic (0.68 versus 0.67, P=0.03) and net reclassification index (4.6%, P=0.04 and 11.3%, P=0.02).Conclusions: Our results show that aortic stiffness predicted major adverse cardiovascular events in a cohort of elderly individuals, improving the performance of a widely used cardiovascular disease risk estimator. Aortic pulse wave velocity measurement is scalable, radiation-free, and easy to perform. Further studies on its applicability in cardiovascular disease risk assessment in primary care settings are needed. [ABSTRACT FROM AUTHOR]

Background: The epidemic of increasing childhood overweight and obesity is a major global health concern, with local contextual factors identified as possible contributors. Robust research is needed to establish an evidence base supporting health policy decisions to reverse the trend. We aimed to examine the association between neighborhood socioeconomic disadvantage and trajectories of body mass index (BMI) from birth to age 7.Methods: The present study included 11,023 children born within the Southwest Finland Birth Cohort who were free of severe conditions affecting growth with adequate exposure and growth data. We obtained child growth data until school age from municipal follow-up clinics. We based cumulative childhood neighborhood socioeconomic disadvantage on the average annual income, unemployment, and level of education in a residential area defined using a geographic grid at a spatial resolution of 250 m by 250 m.Results: Cumulative neighborhood socioeconomic disadvantage was associated with distinct childhood BMI z score trajectories from birth to age 7. Despite being born in the lowest BMI z scores, children growing up in disadvantaged neighborhoods subsequently exhibited a trajectory of increasing BMI z scores starting at 4 years of age, ending up with a higher risk of overweight at the end of the follow-up (30%) as compared with children living in more affluent neighborhoods (22%). The corresponding risk of obesity was 5 % for those in affluent neighborhoods and 9 % and those in disadvantaged neighborhoods.Conclusion: Cumulative exposure to neighborhood socioeconomic disadvantage is independently associated with unfavorable BMI development and obesity in childhood. [ABSTRACT FROM AUTHOR]

Background: Use of electronic health records for ascertainment of disease outcomes in large population-based studies holds much promise due to low costs, diminished study participant burden, and reduced selection bias. However, the validity of cardiovascular disease endpoints derived from electronic records is unclear.Methods: Participants were 7860 study members of the UK Whitehall II cohort study. We compared cardiovascular disease ascertainment using linkage to the National Health Service's Hospital Episode Statistics database records (hereafter, "HES-ascertainment") against repeated biomedical examinations-our gold standard ascertainment method (Whitehall-ascertainment). Follow-up for both methods was from 1997 to 2013 for coronary heart disease and from 1997 to 2009 for stroke.Results: We identified 950 prevalent or incident nonfatal coronary heart disease cases and 118 prevalent or incident nonfatal stroke cases using Whitehall-ascertainment. The corresponding figures for HES-ascertainment were 926 and 107. For coronary heart disease, the sensitivity of HES-ascertainment was 70%, positive predictive value 72%, specificity 96%, and the negative predictive value 96%. The pattern of results for stroke was similar. These statistics did not differ in analyses stratified by age, sex, baseline risk factor status, or after exclusion of prevalent cases. Estimates of risk factor-disease associations were similar between the two ascertainment methods. Including fatal cardiovascular disease in the outcomes improved the agreement between the methods.Conclusion: Our analyses support the validity of cardiovascular disease ascertainment using linkage to the UK Hospital Episode Statistics database records by showing agreement with high resolution disease data collected in the Whitehall II cohort. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Prospective data on depressive symptoms and blood pressure are scarce, and the impact of age on this association is poorly understood. The present study examines longitudinal trajectories of depressive episodes and the probability of hypertension associated with these trajectories over time. Participants were 6889 men and 3413 women, London-based civil servants aged 35 to 55 years at baseline, followed for 24 years between 1985 and 2009. Depressive episode (defined as scoring≥4 on the General Health Questionnaire-Depression subscale or using prescribed antidepressant medication) and hypertension (systolic/diastolic blood pressure≥140/90 mm Hg or use of antihypertensive medication) were assessed concurrently at 5 medical examinations. In the fully adjusted longitudinal logistic regression analyses based on generalized estimating equations using age as the time scale, participants in the "increasing depression" group had a 24% (P<0.05) lower risk of hypertension at ages 35 to 39 years compared with those in the "low/transient depression" group. However, there was a faster age-related increase in hypertension in the increasing depression group, corresponding with a 7% (P<0.01) greater increase in the odds of hypertension for each 5-year increase in age. A higher risk of hypertension in the first group of participants was not evident before 55 years of age. A similar pattern of association was observed in men and women, although it was stronger in men. This study suggests that the risk of hypertension increases with repeated experience of depressive episodes over time and becomes evident in later adulthood. [ABSTRACT FROM AUTHOR]

A promising hypertension risk prediction score using data from the US Framingham Offspring Study has been developed, but this score has not been tested in other cohorts. We examined the predictive performance of the Framingham hypertension risk score in a European population, the Whitehall II Study. Participants were 6704 London-based civil servants aged 35 to 68 years, 31% women, free from prevalent hypertension, diabetes mellitus, and coronary heart disease. Standard clinical examinations of blood pressure, weight and height, current cigarette smoking, and parental history of hypertension were undertaken every 5 years for a total of 4 times. We recorded a total of 2043 incident (new-onset) cases of hypertension in three 5-year baseline follow-up data cycles. Both discrimination (C statistic: 0.80) and calibration (Hosmer-Lemeshow chi(2): 11.5) of the Framingham hypertension risk score were good. Agreement between the predicted and observed hypertension incidences was excellent across the risk score distribution. The overall predicted:observed ratio was 1.08, slightly better among individuals >50 years of age (0.99 in men and 1.02 in women) than in younger participants (1.16 in men and 1.18 in women). Reclassification with a modified score on the basis of our study population did not improve the prediction (net reclassification improvement: -0.5%; 95% CI: -2.5% to 1.5%). These data suggest that the Framingham hypertension risk score provides a valid tool with which to estimate near-term risk of developing hypertension. [ABSTRACT FROM AUTHOR]

Background: Evidence for an association between neighborhood disadvantage and smoking is mixed and mainly based on cross-sectional studies. To shed light on the causality of this association, we examined whether change in neighborhood socioeconomic disadvantage is associated with within-individual change in smoking behaviors.Methods: The study population comprised participants of the Finnish Public Sector study who reported a change in their smoking behavior between surveys in 2008/2009 and 2012/2013. We linked participants' residential addresses to a total population database on neighborhood disadvantage with 250 × 250-m resolution. The outcome variables were changes in smoking status (being a smoker vs. not) as well as the intensity (heavy/moderate vs. light smoker). We used longitudinal case-crossover design, a method that accounts for time-invariant confounders by design. We adjusted models for time-varying covariates.Results: Of the 3,443 participants, 1,714 quit, while 967 began to smoke between surveys. Smoking intensity increased among 398 and decreased among 364 participants. The level of neighborhood disadvantage changed for 1,078 participants because they moved residence. Increased disadvantage was associated with increased odds of being a smoker (odds ratio of taking up smoking 1.23 [95% confidence interval: 1.2, 1.5] per 1 SD increase in standardized national disadvantage score). Odds ratio for being a heavy/moderate (vs. light) smoker was 1.14 (95% confidence interval: 0.85, 1.52) when disadvantage increased by 1 SD.Conclusions: These within-individual results link an increase in neighborhood socioeconomic disadvantage, due to move in residence, with subsequent smoking behaviors. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Background-Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant. Methods and Results--In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: β=-0.0047, P=1.63×10-4; men: β=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r2≥0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0×10-22) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues. Conclusions--Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional analyses of national data have found that persons with high baseline body mass index (BMI) gain weight faster than persons at the median and that those whose weight was below the median gain very little weight. However, it is not clear whether these population-level changes reflect patterns at the individual level.Methods: We examined longitudinal changes in BMI in initially underweight, normal-weight, overweight, and obese US men and women using individual-level repeat data from the Health and Retirement Study (n = 15,895; age range, 40-69 years at baseline). Linear mixed-effect regression was used to model 6-year change in self-reported BMI during 4 study periods (1992/1994-1998/2000, 1996/1998-2002/2004, 2000/2002-2006/2008, and 2004-2010).Results: In the first 6-year period, the mean increase in BMI was greatest among persons who were initially normal weight (0.3 kg/m [95% confidence interval = 0.2 to 0.4]) and overweight (0.2 kg/m [0.1 to 0.3]). Weight gain accelerated in these groups with each subsequent period. Weight gain was less for initially class-I obese participants, and a net decrease in BMI was observed for class-III obese participants.Conclusion: These analyses suggest that the change in mean BMI among middle-aged and older US adults between 1992 and 2010 resulted mainly from accelerated weight gain among persons who were initially normal weight and overweight. [ABSTRACT FROM AUTHOR]

Background: Recent studies based on self-reported data suggest that retirement may have beneficial effects on mental health, but studies using objective endpoints remain scarce. This study examines longitudinally the changes in antidepressant medication use across the 9 years spanning the transition to retirement.Methods: Participants were Finnish public-sector employees: 7138 retired at statutory retirement age (76% women; mean age, 61.2 years), 1238 retired early due to mental health issues (78% women; mean age, 52.0 years), and 2643 retired due to physical health issues (72% women; mean age, 55.4 years). Information on purchase of antidepressant medication 4 years before and 4 years after retirement year was based on comprehensive national pharmacy records in 1994-2005.Results: One year before retirement, the use of antidepressants was 4% among those who would retire at statutory age, 61% among those who would retire due to mental health issues, and 14% among those who would retire due to physical health issues. Retirement-related changes in antidepressant use depended on the reason for retirement. Among old-age retirees, antidepressant medication use decreased during the transition period (age- and calendar-year-adjusted prevalence ratio for antidepressant use 1 year after versus 1 year before retirement = 0.77 [95% confidence interval = 0.68 to 0.88]). Among those whose main reason for disability pension was mental health issues or physical health issues, there was an increasing trend in antidepressant use prior to retirement and, for mental health retirements, a decrease after retirement.Conclusions: Trajectories of recorded purchases of antidepressant medication are consistent with the hypothesis that retirement is beneficial for mental health. [ABSTRACT FROM AUTHOR]

Background: Previous studies report contradictory findings regarding health effects of retirement. This study examines longitudinally the associations of retirement with mental health and physical functioning.Methods: The participants were 7584 civil servants from the Whitehall II cohort study aged 39-64 years at baseline and 54-76 years at the last follow-up. Self-reported mental health and physical functioning were assessed using the Short Form Medical Outcomes Survey questionnaire, and the scales were scored as T-scores (mean [SD] = 50 [10]). Retirement status and health were assessed with 6 repeated measurements over a 15-year period.Results: The associations between retirement and health were dependent on age at retirement, reason for retirement, and length of time spent in retirement. Compared with continued employment, statutory retirement at age 60 and early voluntary retirement, respectively, were associated with 2.2 (95% confidence interval = 1.7 to 2.8) and 2.2 (1.7 to 2.7) points higher mental health and with 1.0 (0.6 to 1.5) and 1.1 (0.8 to 1.4) points higher physical functioning. Retirement due to ill health was associated with poorer mental health (-0.7 points [-1.62 to 0.2]) and physical functioning (-4.5 points [-5.1 to -3.9]). Within-subject analyses suggested a causal interpretation for statutory and voluntary retirement, but health selection for retirement due to ill health.Conclusions: Longitudinal analyses of repeat data suggest that health status improves after statutory and voluntarily retirement, although the improvement seems to attenuate over time. By contrast, the association between retirement due to ill health and subsequent poor health seems to reflect selection rather than causation. [ABSTRACT FROM AUTHOR]

Records of repeated examinations of blood pressure are increasingly available for primary care patients, but the use of this information in predicting incident hypertension remains unclear, because cohort studies with repeat blood pressure monitoring are rare. We compared the incremental value of using data on blood pressure history to a single measure as in the Framingham hypertension risk score, a validated hypertension risk prediction algorithm. Participants were 4314 London-based civil servants (1297 women) aged 35 to 68 years who were free from prevalent hypertension, diabetes mellitus, and coronary heart disease at baseline examination (the Whitehall II Study). Standard clinical examinations of blood pressure, weight and height, current cigarette smoking, and parental history of hypertension were undertaken on a 5-year basis. A total of 1052 incident (new-onset) cases of hypertension were observed in two 5-year baseline follow-up data cycles. Comparison of the Framingham risk score with a score additionally incorporating 5-year blood pressure history showed, at best, modest improvements in indicators of predictive performance: C statistics (0.796 versus 0.799), predicted:observed ratios (1.04 [95% CI: 0.95 to 1.15] versus 0.98 [95% CI: 0.89 to 1.08]), or Hosmer-Lemeshow chi(2) values (11.5 versus 6.5). The net reclassification improvement with the modified score was 9.3% (95% CI: 4.2% to 14.4%), resulting from a net 17.1% increase in nonhypertensives correctly identified as being at lower risk but a net 7.8% increase in hypertensives incorrectly identified as at lower risk. These data suggest that, despite the net reclassification improvement, the clinical use of adding repeat measures of blood pressure to the Framingham hypertension risk score may be limited. [ABSTRACT FROM AUTHOR]

Body weight is associated with reproduction and related behaviors, but it is unknown whether it has significance for fertility differences in the general population. We examined whether adolescent body mass index (BMI; kg/m2) predicted the number of children in adulthood 21 years later.The participants were 1298 Finnish women and men (ages 12, 15, and 18 years at baseline) followed in a prospective population-based cohort study (the Cardiovascular Risk in Young Finns) from year 1980 to 2001.There was an inverted J-shaped association between BMI and the number of children, such that underweight adolescents had 10-16% fewer children in adulthood, overweight adolescents 4-8% fewer, and obese adolescents 32-38% fewer than individuals with normal adolescent weight. This association was similar in women and men, and independent of age, education, urbanicity of residence, and timing of menarche (in women). Adolescents with low or high BMI were less likely to have lived with a partner in adulthood, which partly accounted for their decreased number of children. The influence of adolescent BMI was independent of adulthood BMI in women but not in men. Age at menarche also predicted the number of children, such that women with early or late menarche had more children than those with average age at menarche.Underweight and especially obesity may have a negative impact on fertility in the general population. The increasing prevalence of obesity in children and adolescents may represent a concern for future reproductive health. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Purpose: Transcranial magnetic stimulation-induced motor responses have been considered to mainly reflect the electrophysiological characteristics of the central motor system. However, certain motor phenomena, such as the magnitude of repetition suppression measured with motor evoked potentials (MEPs), could also in part be influenced by metabolic processes in the peripheral muscles and in both the peripheral and central nervous system. Repetition suppression is an inhibitory phenomenon in which the amplitude of MEP decreases in comparison to that of the first MEP in a train of transcranial magnetic stimulation pulses. This study aimed to identify possible metabolic processes influencing repetition suppression., Methods: The metabolic profiles from serum samples and repetition suppression from the right abductor pollicis brevis muscle were measured in 73 subjects (37 female subjects). Repetition suppression was measured using trains of transcranial magnetic stimulation stimuli consisting of 4 identical single pulses at 1-second intervals. The trains were repeated every 20 seconds, and 30 trains were given with a stimulation intensity of 120% of the resting motor threshold of the abductor pollicis brevis. Thus, a total of 120 stimuli were administered., Results: The main finding was a significant negative relationship between serum creatine levels and the magnitude of repetition suppression (standardized β coefficient (β) = -0.43; P < 0.001). In other words, higher creatine levels corresponded to a smaller decrement in the MEP amplitude in response to repetition. When MEPs were not repeated, no relationship was observed (β = 0.09; P = 0.454). Creatine is used to form phosphocreatine, which in turn is needed to resynthesize adenosine triphosphate from adenosine diphosphate in situations requiring high amounts of energy in muscles and neural cells., Conclusions: For the first time, this study demonstrated a connection between repeated MEPs and peripheral serum metabolites linked to muscle function. These findings could explain some of the intersubject variability commonly observed in MEPs when the pulses are repeated.