To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients.
EPIC-NL is a ...prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes-CHD, peripheral arterial disease (PAD), heart failure, and stroke-were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD.
During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06-1.38), PAD (HRSD 1.32 95% CI 1.07-1.65), and heart failure (HRSD 1.75 95% CI 1.42-2.17) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 95% CI 0.94-1.34) or stroke (HRSD 1.05 95% CI 0.73-1.49). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes.
High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.
We studied sleep duration and sleep quality in relation to cardiovascular disease (CVD) incidence.
Dutch population-based cohort study.
20,432 men and women aged 20-65 and with no history of CVD.
...N/A.
Sleep duration and sleep quality were assessed by a self-administered questionnaire. Morbidity data, vital status, and causes of death were obtained through linkage with several national registries. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models.
During 10-15 years of follow-up, 1,486 CVD and 1,148 coronary heart disease (CHD) events occurred. Short sleepers (≤ 6 h) had a 15% higher risk of total CVD (HR: 1.15; 95%CI: 1.00-1.32) and a 23% higher risk of CHD (HR: 1.23 1.04-1.45) compared to normal sleepers (7 h) after adjustment for all confounders. Additional adjustment for intermediate biological risk factors attenuated these relative risks to 1.11 (0.97-1.27) for total CVD and to 1.19 (1.00-1.40) for CHD. Short sleepers with poor sleep quality had a 63% higher risk of CVD (HR: 1.63 1.21-2.19) and a 79% higher risk of CHD incidence (HR: 1.79 1.24-2.58) compared to normal sleepers with good sleep quality, after adjustments for all confounders. We observed no associations between long sleep duration (≥ 9 h) and CVD or CHD incidence.
Short sleepers, especially those with poor sleep quality, have an increased risk of total CVD and CHD incidence. Future investigations should not only focus on sleep duration, but should also take sleep quality into account.
The contribution of sufficient sleep duration to lower CVD risk in addition to sufficient physical activity, a healthy diet, (moderate) alcohol consumption, and non-smoking has not been investigated ...yet.
The MORGEN study is a prospective cohort study including 8128 men and 9759 women aged 20-65 years, free of CVD at baseline.
Sufficient physical activity (≥3.5 h/week cycling or sports), a healthy diet (Mediterranean Diet Score ≥5), (moderate) alcohol consumption (≥1 beverage/month), non-smoking, and sufficient sleep duration (≥7 hours) were assessed by self-administered questionnaires between 1994 and 1997. Cardiovascular morbidity and mortality were ascertained through linkage with national registers. Hazard ratios and preventable proportions were calculated adjusted for age, sex, and educational level.
During 10-14 years of follow up, 607 composite CVD events (fatal CVD, nonfatal myocardial infarction and stroke) occurred, of which 129 were fatal. Those with the four traditional healthy lifestyle factors had a 57% lower risk of composite CVD (HR 0.43, 95% CI 0.31-0.59) and a 67% lower risk of fatal CVD (HR 0.33, 95% CI 0.16-0.68) compared with those with none or one healthy lifestyle factor. Sleeping sufficiently in addition to the four traditional lifestyle factors resulted in a 65% lower risk of composite CVD (HR 0.35, 95% CI 0.23-0.52), and an 83% lower risk of fatal CVD (HR 0.17, 95% CI 0.07-0.43).
Sufficient sleep and adherence to all four traditional healthy lifestyle factors was associated with lower CVD risk. When sufficient sleep duration was added to the traditional lifestyle factors, the risk of CVD was further reduced.
A recent meta-analysis showed that a Mediterranean style diet may protect against cardiovascular diseases (CVD). Studies on disease-specific associations are limited. We evaluated the Mediterranean ...Diet Score (MDS) in relation to incidence of total and specific CVDs.
The EPIC-NL Study is a cohort of 40,011 men and women aged 20-70 years, examined between 1993 and 1997, with 10-15 years of follow-up. Diet was assessed with a validated food frequency questionnaire and the MDS was based on the daily intakes of vegetables, fruits, legumes and nuts, grains, fish, fatty acids, meat, dairy, and alcohol. Cardiovascular morbidity and mortality were ascertained through linkage with national registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) adjusted for age, sex, cohort, smoking, physical activity, total energy intake, and educational level.
In 34,708 participants free of CVD at baseline, 4881 CVD events occurred, and 487 persons died from CVD. A two unit increment in MDS (range 0-9) was inversely associated with fatal CVD (HR: 0.78; 95%CI: 0.69-0.88), total CVD (HR: 0.95 (0.91-0.98)), myocardial infarction (HR: 0.86 (0.79-0.93)), stroke (HR: 0.88 (0.78-1.00)), and pulmonary embolism (HR: 0.74 (0.59-0.92)). The MDS was not related to incident angina pectoris, transient ischemic attack and peripheral arterial disease.
Better adherence to a Mediterranean style diet was more strongly associated with fatal CVD than with total CVD. Disease specific associations were strongest for incident myocardial infarction, stroke and pulmonary embolism.
Objective Shift work is associated with adverse health outcomes, and an unhealthy diet may be a contributing factor. We compared diet quantity and quality between day and shift workers, and studied ...exposure–response relationships regarding frequency of night shifts and years of shift work. Methods Cross-sectional general population data from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort was used. Dietary intake was assessed in 1993–1997 among adults aged 20–70 years using a food frequency questionnaire. We calculated energy intake, the Mediterranean Diet Score (MDS) and WHO-based Healthy Diet Indicator (HDI). In 2011–2014, we retrospectively identified 683 shift workers and 7173 day workers in 1993–1997. Using multivariable-adjusted linear regression analysis, we estimated regression coefficients (β) and 95% confidence intervals (95% CI) of the differences in dietary intake between day and shift workers. Results Shift workers had a higher energy intake than day workers (β:56 kcal/d, 95% CI 10–101), and a higher consumption of grains, dairy products, meat and fish (P<0.05). The difference in energy intake was largest for shift workers with ≥5 night shifts/month. They consumed 103 kcal/d (95% CI 29–176) more than day workers. No associations were found with MDS and HDI. Conclusion Shift workers and particularly those with a high frequency of night shifts had a higher energy intake than day workers. Regardless of number of night shifts and years of shift work, shift workers had similar diet quality as day workers. This suggests that increased energy intake among shift workers may contribute to shift work-induced adverse health outcomes.
There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than Formula: see text) may play an underexplored role in the etiology of several illnesses, including ...cardiovascular disease (CVD).
We aimed o investigate the relationship between long-term exposure to ambient UFP and incident cardiovascular and cerebrovascular disease (CVA). As a secondary objective, we sought to compare effect estimates for UFP with those derived for other air pollutants, including estimates from two-pollutant models.
Using a prospective cohort of 33,831 Dutch residents, we studied the association between long-term exposure to UFP (predicted via land use regression) and incident disease using Cox proportional hazard models. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including particulate matter with aerodynamic diameter Formula: see text (Formula: see text), PM with aerodynamic diameter Formula: see text (Formula: see text), and Formula: see text.
Long-term UFP exposure was associated with an increased risk for all incident CVD Formula: see text per Formula: see text; 95% confidence interval (CI): 1.03, 1.34, myocardial infarction (MI) (Formula: see text; 95% CI: 1.00, 1.79), and heart failure (Formula: see text; 95% CI: 1.17, 2.66). Positive associations were also estimated for Formula: see text (Formula: see text; 95% CI: 1.01, 1.48 per Formula: see text) and coarse PM (Formula: see text; HR for all Formula: see text; 95% CI: 1.01, 1.45 per Formula: see text). CVD was not positively associated with Formula: see text (HR for all Formula: see text; 95% CI: 0.75, 1.28 per Formula: see text). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models (Formula: see text and Formula: see text), positive associations tended to remain for UFP, while HRs for Formula: see text and Formula: see text generally attenuated towards the null.
These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics. https://doi.org/10.1289/EHP3047.
Health examination surveys (HESs), carried out in Europe since the 1950's, provide valuable information about the general population's health for health monitoring, policy making, and research. ...Survey participation rates, important for representativeness, have been falling. International comparisons are hampered by differing exclusion criteria and definitions for non-response.
Information was collected about seven national HESs in Europe conducted in 2007-2012. These surveys can be classified into household and individual-based surveys, depending on the sampling frames used. Participation rates of randomly selected adult samples were calculated for four survey modules using standardised definitions and compared by sex, age-group, geographical areas within countries, and over time, where possible.
All surveys covered residents not just citizens; three countries excluded those in institutions. In two surveys, physical examinations and blood sample collection were conducted at the participants' home; the others occurred at examination clinics. Recruitment processes varied considerably between surveys. Monetary incentives were used in four surveys. Initial participation rates aged 35-64 were 45% in the Netherlands (phase II), 54% in Germany (new and previous participants combined), 55% in Italy, and 65% in Finland. In Ireland, England and Scotland, household participation rates were 66%, 66% and 63% respectively. Participation rates were generally higher in women and increased with age. Almost all participants attending an examination centre agreed to all modules but surveys conducted in the participants' home had falling responses to each stage. Participation rates in most primate cities were substantially lower than the national average. Age-standardized response rates to blood pressure measurement among those aged 35-64 in Finland, Germany and England fell by 0.7-1.5 percentage points p.a. between 1998-2002 and 2010-2012. Longer trends in some countries show a more marked fall.
The coverage of the general population in these seven national HESs was good, based on the sampling frames used and the sample sizes. Pre-notification and reminders were used effectively in those with highest participation rates. Participation rates varied by age, sex, geographical area, and survey design. They have fallen in most countries; the Netherlands data shows that they can be maintained at higher levels but at much higher cost.
The International Initiative on Spatial Lifecourse Epidemiology (ISLE) convened its first International Symposium on Lifecourse Epidemiology and Spatial Science at the Lorentz Center in Leiden, ...Netherlands, 16–20 July 2018. Its aim was to further an emerging transdisciplinary field: Spatial Lifecourse Epidemiology. This field draws from a broad perspective of scientific disciplines including lifecourse epidemiology, environmental epidemiology, community health, spatial science, health geography, biostatistics, spatial statistics, environmental science, climate change, exposure science, health economics, evidence-based public health, and landscape ecology. The participants, spanning 30 institutions in 10 countries, sought to identify the key issues and research priorities in spatial lifecourse epidemiology. The results published here are a synthesis of the top 10 list that emerged out of the discussion by a panel of leading experts, reflecting a set of grand challenges for spatial lifecourse epidemiology in the coming years. https://doi.org/10.1289/EHP4868.
Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations ...remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes.
This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available.
Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation.
Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.
•We studied the effects of long-term exposure to air pollutants on DNA methylation.•A consistent global hypomethylation was observed for exposure to ambient NO2 and NOx.•This hypomethylation was observed for CpG island's shores, shelves and gene bodies.•No CpG sites were epigenome-wide significant in a combined analysis of a low and high exposed cohort.
To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In ...the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43–70 years at baseline (1995–2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.
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