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Background: Individuals who had normoglycemia but whose 2-hour plasma glucose (2hPG) concentrations did not return to the fasting plasma glucose (FPG) levels during an oral glucose tolerance test (OGTT) have been shown to have increased cardiovascular mortality. This is further investigated regarding to the first events of coronary heart disease (CHD) and ischemic stroke (IS)., Method: Data from 9 Finnish and Swedish cohorts comprising 3743 men and 3916 women aged 25 to 90  years who had FPG < 6.1 mmol/l and 2hPG < 7.8 mmol/l and free of CVD at enrollment were analyzed. Hazard ratios (HRs) for first CHD and IS events were estimated for the individuals with 2hPG > FPG (Group II) compared with those having 2hPG ≤ FPG (Group I)., Results: A total of 466 (115) CHD and 235 (106) IS events occurred in men (women) during a median follow-up of 16.4 years. Individuals in Group II were older and had greater body mass index, blood pressure, 2hPG and fasting insulin than those in Group I in both sexes. Multivariate adjusted HRs (95% confidence intervals) for incidence of CHD, IS, and composite CVD events (CHD + IS) in men were 1.13 (0.93-1.37), 1.40 (1.06-1.85) and 1.20 (1.01-1.42) in the Group II as compared with those in the Group I. The corresponding HRs in women were 1.33 (0.83-2.13), 0.94 (0.59-1.51) and 1.11 (0.79-1.54), respectively., Conclusion: Within normoglycemic range individuals whose 2hPG did not return to their FPG levels during an OGTT had increased risk of CHD and IS.

Background: We studied the age and gender difference between acute coronary heart disease and ischaemic stroke risk and examined the extent to which such a difference may be explained by known risk factors., Methods: Data from Finnish and Swedish population-based cohorts including 9278 individuals were collaboratively analysed. Hazards ratios (95% confidence intervals) for coronary heart disease and stroke incidence were estimated using the Cox-proportional hazards model., Results: The incidence of coronary heart disease and stroke was higher in all age groups in men than in women, and the gender difference was more marked for coronary heart disease than for ischaemic stroke. There was a 10-year lag in the development of coronary heart disease and stroke in women compared with men. The multivariable adjusted hazard ratios for the incidence of coronary heart disease in men and women were 3.87 (2.49-6.02) and 1.71 (1.07-2.74) at age 50-59 years, and 7.22 (4.59-11.36) and 3.49 (2.18-5.57) at age 60-69 years compared with women aged 40-49 years. For ischaemic stroke, they were 2.64 (1.45-4.82) and 2.17 (1.18-3.97) at age 50-59 years, and 5.19 (2.81-9.58) and 4.89 (2.67-8.97) at age 60-69 years, respectively., Conclusions: Acute coronary heart disease and ischaemic stroke events appeared approximately 10 years earlier in men than in women, and these rates remained higher in men than in women in all age groups. The gender difference was more marked for coronary heart disease than for ischaemic stroke. This may be taken into account when developing interventions and treatment strategies.

Objective: Activating transcription factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We used a 2-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD)., Methods and Results: In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for familial combined hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9 x 10(-4)), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter., Conclusions: A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm the role of this variant in lipids.

Background and Purpose: We examined the impact of hyperglycemia on ischemic and hemorrhagic stroke incidence comparing criteria based on fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hour PG)., Methods: Data from 9 European cohorts comprising 18 360 individuals between 25 to 90 years of age were collaboratively analyzed. The maximum length of follow-up varied between 4.9 to 36.8 years. Hazards ratios (95% confidence intervals) for stroke incidence were estimated using Cox-proportional hazards model adjusting for known risk factors., Results: In individuals without a prior history of diabetes, the multivariate-adjusted hazards ratio for ischemic stroke corresponding to 1 SD increase in FPG was 1.12 (1.02 to 1.22) and in 2-hour PG 1.14 (1.05 to 1.24). Adding 2-hour PG to the model with FPG significantly improved the prediction of the model for the incidence of ischemic stroke (chi(2)=4.72, P=0.03), whereas FPG did not improve the 2-hour PG model prediction (chi(2)=0.25, P=0.62). A significantly increased hazard ratio was also observed for previously diagnosed diabetes (2.26 [1.51 to 3.38]) and for screen-detected diabetes defined by FPG (1.48 [1.08 to 2.02]) and 2-hour PG (1.60 [1.18 to 2.16]). None of the criteria predicted hemorrhagic stroke., Conclusions: Diabetes defined by either of the criteria predicted the future risk of ischemic stroke but not the hemorrhagic stroke. The prediction is stronger for elevated 2-hour PG than for FPG levels.