Person:

Buring, Julie

Objectives: To evaluate the association between restless legs syndrome (RLS) and all-cause mortality. Design: Four prospective cohort studies. Setting: The Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from Germany. The Women's Health Study (WHS) and the Physicians’ Health Study (PHS) from the USA. Participants: In DHS: a random sample (n=1 299) from the population of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania were drawn by multistage random sampling design; in WHS: female healthcare professionals (n=31 370); in PHS: male physicians (n=22 926) Main outcome measures: All-cause mortality. Results: The prevalence of RLS ranged between 7.4% and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was not associated with increased risk of all-cause mortality in any of the four cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs for all-cause mortality did not differ according to gender. Conclusions: In these four independently conducted large prospective cohort studies from Germany and the USA, RLS did not increase the risk of all-cause mortality. These findings do not support the hypothesis that RLS is a risk factor for mortality of any cause.

Background: Individuals with Parkinson's disease (PD) may have an increased risk of overall mortality compared to the general population. Women may have lower mortality rates from PD than men; however, studies among women on the effect of PD on mortality have been limited and may not have adequately controlled for confounding by comorbidities. Methods: We conducted a matched cohort study among participants in the Women's Health Study. 396 incident PD cases were identified through self-report. Each PD case was matched by age to a comparator who was alive and had the same modified Charlson comorbidity score as the PD case. The PD cases and matched comparators were followed for all-cause mortality. Cox proportional hazards models adjusted for age at the index date, smoking, alcohol consumption, exercise and body mass index were used to determine the association between PD and mortality. Results: During a median of 6.2 years of follow-up, 72 women died (47 PD cases and 25 comparators). The multivariable-adjusted HR for mortality was 2.60 (95% CI 1.56 to 4.32). Conclusions: PD was associated with more than a twofold increased risk of all-cause mortality among women. Results are similar to those observed among men.

Background: Limited data exist directly comparing the relative benefits of moderate‐ and vigorous‐intensity activities with all‐cause and cardiovascular (CV) disease mortality rates when controlling for physical activity volume. Methods and Results: We followed 7979 men (Harvard Alumni Health Study, 1988–2008) and 38 671 women (Women's Health Study, 1992–2012), assessing their physical activity and health habits through repeated questionnaires. Over a mean follow‐up of 17.3 years in men and 16.4 years in women, there were 3551 deaths (1077 from CV disease) among men and 3170 deaths (620 from CV disease) among women. Those who met or exceeded an equivalent of the federal guidelines recommendation of at least 150 minutes of moderate‐intensity activity, 75 minutes of vigorous‐intensity activity, or a combination of the 2 that expended similar energy experienced significantly lower all‐cause and CV disease–related mortality rates (men, 28% to 36% and 31% to 34%, respectively; women: 38% to 55% and 22% to 44%, respectively). When comparing different combinations of moderate‐ and vigorous‐intensity activity and all‐cause mortality rates, we observed sex‐related differences. Holding constant the volume of moderate‐ to vigorous‐intensity physical activity, men experienced a modest additional benefit when expending a greater proportion of moderate‐ to vigorous‐intensity physical activity in vigorous‐intensity activities (Ptrend=0.04), but women did not (Ptrend<0.001). Moderate‐ to vigorous‐intensity physical activity composition was not associated with further cardiovascular mortality rate reductions in either men or women. Conclusions: The present data support guidelines recommending 150 minutes of moderate‐intensity activity per week, 75 minutes of vigorous‐intensity activity per week, or an equivalent combination for mortality benefits. Among men, but not women, additional modest reductions in all‐cause mortality rates are associated with a greater proportion of moderate‐ to vigorous‐intensity physical activity performed at a vigorous intensity.

Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0–10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women’s Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00–1.03), p = 0.17), breast (n = 1560; 1.02 (0.99–1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00–1.13), p = 0.07), lung (n = 330; 1.00 (0.94–1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96–1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality.