AbstractObjectiveTo investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.DesignProspective case-cohort ...study.SettingPopulations from eight European countries.Participants9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measureIncident type 2 diabetes.ResultsIn a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.ConclusionsThese findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
Objective To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population.Design Systematic review.Data sources Medline and Embase until June ...2013.Eligibility criteria for study selection Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population.Results 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively.Conclusions There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local settings, and investigating whether these models can be extended by addition of new predictors.
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.
All blood cells (white blood cells WBC, red blood cells RBC and platelets) can play a role in atherosclerosis. Complete blood count (CBC) is widely available in clinical practice but utility as ...potential risk factors for cardiovascular disease (CVD) is uncertain. Our aim was to assess the associations of pre-diagnostic CBC with incidence of CVD in 14,362 adults free of CVD and aged 47.8 (±11.7) years at baseline, followed-up for 11.4 years (992 incident cases). Cox proportional hazards regressions were used to estimate HRs and 95%CI. Comparing the top (T3) to bottom (T1) tertile, increased total WBC, lymphocyte, monocyte and neutrophil counts were associated with higher CVD risk: 1.31 (1.10; 1.55), 1.20 (1.02; 1.41), 1.21 (1.03; 1.41) and 1.24 (1.05; 1.47), as well as mean corpuscular volume (MCV: 1.23 1.04; 1.46) and red cell distribution width (RDW: 1.22 1.03; 1.44). Platelets displayed an association for count values above the clinically normal range: 1.49 (1.00; 2.22). To conclude, total and differential WBC count, MCV, RDW and platelet count likely play a role in the aetiology of CVD but only WBC provide a modest improvement for the prediction of 10-year CVD risk over traditional CVD risk factors in a general population.
Abstract
Context
Anti-Müllerian hormone (AMH) levels are used worldwide as a screening tool for the duration of the female reproductive lifespan. Although AMH levels are associated with age at ...menopause, individual predictions of menopause with a single AMH measurement are unreliable.
Objective
This study investigated whether individual AMH decline patterns can improve the prediction of menopause compared with a single measurement.
Design
The study population comprised 2434 premenopausal women from the population-based Doetinchem Cohort Study. Participants were followed up every 5 years for a total of 20 years, and AMH was measured in 6699 plasma samples with the picoAMH assay. Longitudinal statistical modeling was combined with time varying Cox modeling, to integrate multiple AMH measurements per woman.
Results
The mean age at menopause was 50 years, and 7.4% of the women who reached menopause during follow-up did so before age 45 years. For a 25-year-old, the AMH decline rate between ages 20 and 25 years increased the C-statistic of menopause prediction from 0.64 to 0.69. Beyond that age, the AMH decline rate did not improve predictions of menopause or early menopause. For women younger than age 30 years, for whom menopause prediction is arguably most relevant, the models underestimated the risk of early menopause.
Conclusion
These results suggest that knowledge of the AMH decline rate does not improve the prediction of menopause. Based on the low discriminative ability and underestimation of the risk of early menopause, the use of AMH as a screening method for the timing of menopause cannot currently be advocated.
Compared with a single AMH measurement, the use of serial AMH measurements does not improve the prediction of menopause.
The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between ...undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944-1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI 1.09-1.70); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26-2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood.
Purpose
The association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk ...based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients.
Methods
37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates.
Results
893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85–0.99), myristic acid (0.89, 0.79–0.99), margaric acid (0.84, 0.73–0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79–0.99), and cheese derived SFA (0.90, 0.83–0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01–1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15).
Conclusion
In this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by
trans
fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.
Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association ...between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40–44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women.
This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian).
This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women.
A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0–52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77–4.17) and 1.42 (1.15–1.74) for women with infertility; 1.31 (1.08–1.59) and 1.37 (1.14–1.65) for women with recurrent miscarriages; and 1.54 (1.52–1.56) and 1.39 (1.35–1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history.
Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.
Abstract Background and aims CVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to ...assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality. Methods We conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality. Results In the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 95% CI 1.50–21.41). Conclusions Risk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology.
Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy.
To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based ...menopause prediction.
A systematic literature search was performed using PubMed, Embase and Cochrane databases.
Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion.
Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery.
2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age.
AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.
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