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Aims/hypothesis: The euglycaemic-hyperinsulinaemic clamp (EIC) is the reference standard for the measurement of whole-body insulin sensitivity but is laborious and expensive to perform. We aimed to assess the incremental value of high-throughput plasma proteomic profiling in developing signatures correlating with the M value derived from the EIC., Methods: We measured 828 proteins in the fasting plasma of 966 participants from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study and 745 participants from the Uppsala Longitudinal Study of Adult Men (ULSAM) using a high-throughput proximity extension assay. We used the least absolute shrinkage and selection operator (LASSO) approach using clinical variables and protein measures as features. Models were tested within and across cohorts. Our primary model performance metric was the proportion of the M value variance explained (R 2 )., Results: A standard LASSO model incorporating 53 proteins in addition to routinely available clinical variables increased the M value R 2 from 0.237 (95% CI 0.178, 0.303) to 0.456 (0.372, 0.536) in RISC. A similar pattern was observed in ULSAM, in which the M value R 2 increased from 0.443 (0.360, 0.530) to 0.632 (0.569, 0.698) with the addition of 61 proteins. Models trained in one cohort and tested in the other also demonstrated significant improvements in R 2 despite differences in baseline cohort characteristics and clamp methodology (RISC to ULSAM: 0.491 [0.433, 0.539] for 51 proteins; ULSAM to RISC: 0.369 [0.331, 0.416] for 67 proteins). A randomised LASSO and stability selection algorithm selected only two proteins per cohort (three unique proteins), which improved R 2 but to a lesser degree than in standard LASSO models: 0.352 (0.266, 0.439) in RISC and 0.495 (0.404, 0.585) in ULSAM. Reductions in improvements of R 2 with randomised LASSO and stability selection were less marked in cross-cohort analyses (RISC to ULSAM R 2 0.444 [0.391, 0.497]; ULSAM to RISC R 2 0.348 [0.300, 0.396]). Models of proteins alone were as effective as models that included both clinical variables and proteins using either standard or randomised LASSO. The single most consistently selected protein across all analyses and models was IGF-binding protein 2., Conclusions/interpretation: A plasma proteomic signature identified using a standard LASSO approach improves the cross-sectional estimation of the M value over routine clinical variables. However, a small subset of these proteins identified using a stability selection algorithm affords much of this improvement, especially when considering cross-cohort analyses. Our approach provides opportunities to improve the identification of insulin-resistant individuals at risk of insulin resistance-related adverse health consequences., (© 2023. The Author(s).)

Importance: Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD., Objective: To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes., Design, Setting, and Participants: This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016., Exposures: Treatment with GnRH agonists and PCa diagnosis were the primary exposures., Main Outcomes and Measures: Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association., Results: The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82)., Conclusions and Relevance: In this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

Background: Self-reported leisure-time physical activity (PA) has previously been linked to risk of cardiovascular disease (CVD). We now aim to investigate the strength of associations between PA and different CVDs and how the risk varies with age., Methods: PA and traditional CV risk factors assessed by a questionnaire on a four-level scale in 2,175 men at age 50 years in the ULSAM study. Examinations were thereafter repeated at ages 60, 70, and 77., Results: During 40 years follow-up, 883 individuals experienced a CVD (myocardial infarction, stroke, or heart failure). Using data from all four examinations, a graded reduction in risk of incident CVD was seen with increasing PA (HR 0.84, 95%CI; 0.77-0.93, p = 0.001 for trend test). PA was related to myocardial infarction (HR 0.84, 95%CI; 0.74-0.95, 490 cases), heart failure (HR 0.79, 95%CI; 0.68-0.91, 356 cases), but only of borderline significance vs ischemic stroke (HR 0.85, 95%CI; 0.73-1.00, 315 cases) when the CVDs were analyzed separately. Adjusting for traditional CV risk factors attenuated all relationships between PA and incident CVD, and PA did not improve discrimination of CVD when added on top of risk factors. When 10-year risk was calculated from each examination, age 70 was the time-point when PA was most closely related to incident CVD., Conclusion: Leisure-time physical activity is related to future CVD. This was most evident at 70 years of age. If a causal relationship between self-reported PA and CVD exists, this relationship might to a major degree be mediated by traditional risk factors., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate how self-reported leisure-time physical activity (PA) changes during the adult life span, and to study how PA is related to cardiovascular risk factors using longitudinal studies., Methods: Several Swedish population-based longitudinal studies were used in the present study (PIVUS, ULSAM, SHE, and SHM, ranging from hundreds to 30,000 participants) to represent information across the adult life span in both sexes. Also, two cross-sectional studies were used as comparison (EpiHealth, LifeGene). PA was assessed by questionnaires on a four or five-level scale., Results: Taking results from several samples into account, an increase in PA from middle-age up to 70 years was found in males, but not in females. Following age 70, a decline in PA was seen. Young adults reported both a higher proportion of sedentary behavior and a higher proportion high PA than the elderly. Females generally reported a lower PA at all ages. PA was mainly associated with serum triglycerides and HDL-cholesterol, but also weaker relationships with fasting glucose, blood pressure and BMI were found. These relationships were generally less strong in elderly subjects., Conclusion: Using data from multiple longitudinal samples the development of PA over the adult life span could be described in detail and the relationships between PA and cardiovascular risk factors were portrayed. In general, a higher or increased physical activity over time was associated with a more beneficial cardiovascular risk factor profile, especially lipid levels., Competing Interests: The authors have declared that no competing interests exist.

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD)., Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n = 576)., Results: Participants with a high TG/HDL-C ratio (highest quartile >1.8) at baseline were more insulin resistant, with a significantly more adverse cardiometabolic risk profile (P < 0.001) at baseline, compared with those with a lower ratio. This group also showed an increased risk of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26-1.93) P < 0.001]. Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance is increased, were also at enhanced CVD risk [HR 1.75 (1.42-2.16) P < 0.001]., Conclusions: Twenty-five percent of apparently healthy 50-year-old men with the highest TG/HDL-C plasma concentration ratio had a significantly more adverse cardiometabolic profile at baseline, and developed more CVD over the next 40 years, compared with those not meeting this cut point. Determining the TG/HDL-C ratio in middle-aged men provided a simple and potentially clinically useful way to identify increased risk of developing CVD in persons free of diabetes or manifest CVD.

Background: Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated., Methods: In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes., Results: The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death., Conclusions: Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.).

Aim: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers., Research Design and Methods: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score., Results: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF., Conclusions: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality., (© 2016 John Wiley & Sons Ltd.)

Objectives: Assess the effect of risk factors changes on risk for cardiovascular disease and mortality in patients with type 2 diabetes selected from the Swedish National Diabetes Register., Methods: Observational study of 13,477 females and males aged 30-75 years, with baseline HbA1c 41-67 mmol/mol, systolic blood pressure 122-154 mmHg and ratio non-HDL:HDL 1.7-4.1, followed for mean 6.5 years until 2012. Four groups were created: a reference group (n = 6757) with increasing final versus baseline HbA1c, systolic blood pressure and non-HDL:HDL cholesterol during the study period, and three groups with decreasing HbA1c (n = 1925), HbA1c and systolic blood pressure (n = 2050) or HbA1c and systolic blood pressure and non-HDL:HDL (n = 2745)., Results: Relative risk reduction for fatal/nonfatal cardiovascular disease was 35% with decrease in HbA1c only (mean 6 to final 49 mmol/mol), 56% with decrease in HbA1c and systolic blood pressure (mean 12 to final 128 mmHg) and 75% with combined decreases in HbA1c, systolic blood pressure and non-HDL:HDL (mean 0.8 to final 2.1), all p < 0.001 adjusting for clinical characteristics, other risk factors, treatments and previous cardiovascular disease. Similar risk reductions were found for fatal/nonfatal coronary heart disease, fatal cardiovascular disease, all-cause mortality and also in a subgroup of 3038 patients with albuminuria., Conclusion: Considerable risk reductions for cardiovascular disease and mortality were seen with combined long-term risk factor improvement., (© The Author(s) 2016.)

Aim: The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear., Methods: One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose×log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0×insulin0×glucose120×insulin120]; Belfiore-IR: 1/([glucose0+glucose120]/normal mean glucose×[insulin0+insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0×insulin0]/22.5., Results: Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk., Conclusion: Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Improvement of risk prediction for atherosclerotic cardiovascular disease (ASCVD) is needed. Both ambulatory blood pressure (ABP) and biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein and cystatin C improve risk prediction but they have not been evaluated in relation to each other. We analyzed whether NT-proBNP, high-sensitivity C-reactive protein, or cystatin C improved risk prediction beyond traditional ASCVD risk factors combined with 24-hour systolic BP (SBP). Secondary aim was to evaluate whether ABP improved risk prediction when compared with models with the biomarkers. We followed up 907 70-year-old men, free of baseline disease, for incident ASCVD defined as fatal or nonfatal myocardial infarction or fatal or nonfatal stroke for a median of 10 years. Cox regression was used to estimate the association between variables in the models and incident ASCVD. Biomarkers were added to a model containing both traditional risk factors and ABP and the models were compared on C-statistics and net reclassification improvement. Twenty-four hour SBP improved discrimination for incident ASCVD when compared with office SBP in a traditional risk factor model (area under the receiver-operating characteristic curve, +2.4%). NT-proBNP further improved reclassification (+18.7%-19.9%; P<0.01) when added to ABP models, whereas high-sensitivity C-reactive protein and cystatin C did not. Twenty-four hour SBP significantly improved net reclassification when added to a traditional risk factor model that included NT-proBNP. The combination of 24-hour SBP and NT-proBNP improved discrimination and net reclassification for incident ASCVD when compared with office SBP in elderly men. NT-proBNP, but not high-sensitivity C-reactive protein or cystatin C, improved risk prediction and discrimination when added to a model that included ABP., (© 2015 American Heart Association, Inc.)

Objective: To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes., Design: Observational study., Setting: Swedish National Diabetes Register, Sweden 2005-12., Participants: 18,168 people with type 1 diabetes, 2441 using insulin pump therapy and 15,727 using multiple daily insulin injections., Main Outcome Measures: Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases., Results: Follow-up was for a mean of 6.8 years until December 2012, with 114,135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association., Conclusion: Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections., (© Steineck et al 2015.)

Background: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender., Methods: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale., Results: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and ≥35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals., Conclusions: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.

The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.

Objective: Reduced renal function and albuminuria predict cardiovascular (CV) events and mortality in type 2 diabetes (T2D). In addition, we evaluated the role of co-existing congestive heart failure (CHF) and other CV risk factors on CV events in a large observational population-based cohort of T2D patients., Research Design and Methods: We included 66,065 patients with T2D who were reported to the National Diabetes Register (NDR) in Sweden between 2003-2006 with a follow-up of 5.7 years. Data on outcomes were collected from the cause of death and hospital discharge registers., Results: A total of 10% of patients experienced a CV event and 3.7% of these were fatal. Increasing levels of albuminuria and renal impairment were independently associated with increasing risk of CV events and all-cause mortality also when adjusting for CHF. In normoalbuminuric patients, a reduction in renal function is an important predictor of CV events and all-cause mortality. Glycaemic control (high HbA1c), smoking and hyperlipidaemia had important effects on risk for CV events in patients with albuminuria, while high blood pressure, but not glycaemic control, had an effect in patients with normoalbuminuric renal impairment., Conclusion: Albuminuria and renal impairment are independent risk factors for CV outcomes and mortality in T2D, albuminuria being the strongest risk factor and relevant at all levels of renal function. In normoalbuminuric patients, a reduction in renal function is an important predictor of CV events and all-cause mortality.

Background: Cardiac troponin is emerging as risk indicator in community-dwelling populations. In this study, we investigated the associations of cardiac troponin T (cTnT) to cardiovascular (CV) disease and outcome in elderly men., Methods: Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71 years participating in the Uppsala Longitudinal Study of Adult Men. We assessed both the cross-sectional associations of cTnT to CV risk factors and morbidities including cancer and the longitudinal associations to outcomes over 10 years of follow-up., Results: Cardiac troponin T levels were measurable in 872 subjects (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial fibrillation and coronary artery disease, and biomarkers of inflammation and left ventricular dysfunction. In the longitudinal analyses, cTnT independently predicted total mortality and CV events including stroke. The standardized adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3-1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P = .02, for men without. Cardiac troponin T improved discrimination metrics for all outcomes in the total population. This was mainly driven by the prognostic value of cTnT in subjects with prevalent CV disease., Conclusions: In community-dwelling men, cTnT levels are associated to CV risk factors and morbidities and predict both fatal and nonfatal CV events. The relations to outcome are mainly seen in men with prevalent CV disease indicating that the prognostic value of cTnT in subjects free from CV disease is limited., (© 2013.)

Objectives: Estimate risks of coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with updated mean systolic (SBP) and diastolic (DBP) blood pressure in an observational study of patients with type 2 diabetes., Methods: Thirty-five thousand and forty-one patients treated with antihypertensive drugs, and 18 512 untreated patients, aged 30-75 years, without previous heart failure, followed for 6 years until 2009., Results: In treated patients, nonlinear splines for 6-year risk of fatal/nonfatal CHD, stroke and CVD by BP as a continuous variable showed a progressive increase with higher SBP from 140  mmHg and higher, and with DBP from 80  mmHg, with a J-shaped risk curve at lowest SBP levels, but not obviously at lowest DBP levels. Analysing intervals of SBP with 130-134  mmHg as reference at Cox regression, adjusted hazard ratios (HR) for fatal/nonfatal CHD, stroke and CVD with at least 140  mmHg were 1.22 [95% confidence interval (CI): 1.08-1.39], 1.43 (1.18-1.72), 1.26 (1.13-1.41), all P < 0.001. HR with 115-129 and 135-139  mmHg were nonsignificant, whereas increased with 100-114  mmHg, 1.96 (P < 0.001), 1.75 (P = 0.02), 2.08 (P < 0.001), respectively. With DBP 75-79  mmHg as reference, adjusted HR for fatal/nonfatal CHD, stroke and CVD with DBP 80-84  mmHg were 1.42 (1.26-1.59), 1.46 (1.24-1.72), 1.39 (1.26-1.53), all P < 0.001. Corresponding HR with DBP at least 85  mmHg were 1.70 (1.50-1.92), 2.35 (1.99-2.77), 1.87 (1.69-2.07), all P < 0.001. Corresponding HR with DBP 60-69 and 70-74  mmHg were nonsignificant. The picture was similar in 7059 patients with previous CVD and in untreated patients., Conclusion: BP around 130-135/75-79  mmHg showed lower risks of cardiovascular diseases in patients with type 2 diabetes.

Background: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce., Methods: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths)., Results: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73 m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73 m(2) significantly improved IDI (0.047, P < 0.001)., Conclusions: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

Aim: We assessed the association between risk factors and cardiovascular disease (CVD) in an observational study of type 2 diabetes patients from the Swedish National Diabetes Register., Methods: A derivation sample of 24,288 patients, aged 30-74 years, 15.3% with previous CVD, baseline 2002, 2488 CVD events when followed for 5 years until 2007. A separate validation data set of 4906 patients, baseline 2003, 522 CVD events when followed for 4 years., Results: Adjusted hazard ratios at Cox regression for fatal/nonfatal CVD were: onset-age 1.59, diabetes duration 1.55, total-cholesterol-to-HDL-cholesterol ratio 1.20, HbA1c 1.12, systolic BP 1.09, BMI 1.07 (1 SD increase in natural log continuous variables); males 1.41, smoker 1.35, microalbuminuria 1.27, macroalbuminuria 1.53, atrial fibrillation 1.50, previous CVD 1.98 (all p<0.001 except BMI p=0.0018). All 12 variables were used to elaborate an equation for 5-year CVD risk in the derivation dataset: mean 5-year risk 11.9±8.4%. Calibration in the validation dataset was adequate: ratio predicted 4-year risk/observed rate 0.97. Discrimination was sufficient: C statistic 0.72, sensitivity 51% and specificity 78% for top quartile., Conclusion: This CVD risk model from a large observational study of patients in routine care showed adequate calibration and discrimination, and can be useful for clinical practice., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: Our aim was to evaluate the longitudinal associations of individual and multiple vascular risk factors with the subsequent development of dementia and Alzheimer's disease (AD)., Methods: The Uppsala Longitudinal Study of Adult Men started in 1970 when the 2,268 participants were 50 years old. Baseline investigations included determinations of blood pressure, fasting glucose, cholesterol, BMI and smoking status. Over a maximum follow-up of 40 years, 349 participants were diagnosed with dementia, out of which 127 had AD. Analyses were repeated using a re-examination of the cohort at 70 years of age as a baseline., Results: No associations between vascular risk factors and AD were found. For all-type dementia, the association between high systolic blood pressure and dementia was the most consistent. High fasting glucose was associated with increased risk of all-type dementia only when measured at 70 years. Individuals with both an APOE ε4 allele and vascular risk factors had the greatest dementia risk., Conclusion: Vascular risk factors influence the future risk of dementia, in particular vascular and mixed-type rather than AD. The impact of vascular risk factors on dementia in a longitudinal study depends on the age at baseline and the length of follow-up., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: To estimate risks of fatal/nonfatal coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with SBP in an observational study of patients with type 2 diabetes., Methods: Twelve thousand, six hundred and seventy-seven patients aged 30-75 years, treated with antihypertensive drugs, without previous congestive heart failure, followed for 5 years., Results: Risk curves of CHD and stroke increased progressively with higher baseline or updated mean SBP in a Cox model, in all participants, and in two subgroups without (n = 10 304) or with (n = 2373) a history of CVD, with no J-shaped risk curves at low SBP levels. Hazard ratios for CHD and stroke per 10-mmHg increase in updated mean SBP in all participants, adjusting for clinical characteristics and traditional risk factors, were 1.08 (1.04-1.13) and 1.20 (1.13-1.27), P < 0.001. With updated mean SBP of 110-129 mmHg as reference, SBP of at least 140 mmHg showed risk increases of 37% for CHD, 86% for stroke and 44% for CVD (P = 0.001 to <0.001), whereas SBP of 130-139 mmHg showed nonsignificant risk increases for these outcomes. With baseline SBP of 110-129 mmHg, CHD and CVD risks increased with further SBP reduction, hazard ratios were 1.77 and 1.73 (P = 0.002), but decreased considerably for CHD, stroke and CVD with higher baseline SBP., Conclusion: Risks of CHD and stroke increased progressively with higher SBP, with no J-shaped curves, although risk increase was significant only for SBP of at least 140 mmHg, but not comparing 130-139 and 110-129 mmHg. Additionally, baseline SBP of 110-129 mmHg showed increased CHD and CVD risk with further SBP reduction during follow-up, whereas baseline SBP of at least 130 showed benefits.

Aim: To estimate hazard ratio (HR) of first incident fatal/non-fatal cardiovascular diseases (CVD) in female/male type 2 diabetic patients, with tight versus adverse control of HbA1c and blood pressure (BP) at baseline, age 30-70 years, no baseline CVD, followed for mean 5.7 years., Methods: 2593 patients with tight control of HbA1c <7.5% and BP < or = 140/90 mmHg (median 6.5%/130/80 mmHg), and 2160 patients with adverse control 7.5-9.0%/141-190/91-110 mmHg (median 8.1%/155/85 mmHg)., Results: The hazard ratio (HR) for CVD with tight/adverse control was 0.67 (0.55-0.80; p<0.001), adjusting for age, sex, duration, hypoglycaemic treatment, smoking, BMI, lipid-lowering drugs, antihypertensive drugs, microalbuminuria. Adjusted HR for myocardial infarction, coronary heart disease, stroke and total mortality were 0.72 (0.56-0.92; p=0.01), 0.69 (0.55-0.86; p<0.001), 0.62 (0.45-0.84; p<0.001), 1.00 (0.72-1.39). The partial population-attributable risk percent for myocardial infarction, stroke and CVD was 23%, 33%, 29% if adverse HbA1c/BP control could be avoided, while 43%, 38%, 39% with overweight and smoking also avoided. Baseline lower BMI and absence of microalbuminuria were associated with tight control., Conclusion: Median difference of HbA1c/BP 1.6%/25/5 mmHg between tight and adverse control considerably reduced the risk of cardiovascular diseases. The findings call for a multi-factorial approach to improve HbA1c, BP, obesity, smoking, and microalbuminuria.

Objective: To evaluate the impact of dyslipidaemia on cardiovascular disease (CVD) mortality in relation to fasting (FPG) and 2-h (2hPG) plasma glucose levels in individuals without a prior history of diabetes., Methods: Data from 14 European population-based prospective studies of 9132 men and 8631 women aged 25-89 years were jointly analysed. A total of 871 CVD deaths occurred during the average 10 years of follow-up. Subjects were classified into normoglycaemia, isolated fasting hyperglycaemia (IFH, FPG> or =6.10 mmol/l and 2hPG<7.80 mmol/l), isolated post-load hyperglycaemia (IPH, FPG<6.10 mmol/l and 2hPG> or =7.80 mmol/l) and combined fasting and post-load hyperglycaemia (CH, FPG> or =6.10 mmol/l and 2hPG> or =7.80 mmol/l). Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard analysis., Results: Multivariate-adjusted HRs (95% CIs) for high-density lipoprotein cholesterol (HDL-C) were 0.84 (0.75-0.94), 0.66 (0.48-0.92), 1.03 (0.84-1.27) and 0.67 (0.51-0.89) in individuals with normoglycaemia, IFH, IPH and CH, respectively. For total cholesterol (TC) to HDL-C ratio they were 1.14 (1.03-1.27), 1.44 (1.13-1.84), 0.94 (0.77-1.15) and 1.26 (1.05-1.50), respectively. HRs for TC and triglycerides (TG) were not significant in most of the glucose categories except for TG in those with CH [HR 1.12 (1.00-1.27)]., Conclusions: Low HDL-C and high TC/HDL-C increase CVD mortality in either diabetic or non-diabetic individuals defined based on the fasting glucose criteria, but not the 2-h criteria. TG is a significant CVD risk predictor only in the presence of combined hyperglycaemia or diabetes. The difference between fasting and post-load hyperglycaemia with regard to the lipid-CVD relation may suggest a different pathophysiology underlying these two prediabetic states.

Background: Hypersensitive cardiac troponin I (cTnI) assays detect even minor elevations of cTnI. Previous findings identifying a group of seemingly healthy elderly men with very minor elevations of cTnI have shown that these men were at risk of premature cardiovascular death., Objectives: To study the association between cTnI concentrations and cardiovascular risk factors and subclinical cardiac and renal target organ damage in a community-based sample of elderly men., Methods: Biomarkers reflecting glucose and lipid metabolism, renal function, cardiac function and inflammation were measured in the ULSAM study (n = 1205, mean age 71 years). The participants were placed in three subgroups based on the cTnI concentrations: a low group with cTnI <0.02 microg/L, an intermediate group with cTnI between 0.02 and 0.039 microg/L and a high group with cTnI >0.039 microg/L., Results: In the entire cohort of 71-year-old men, most markers of glucose and lipid metabolism, renal function, inflammation and NT-proBNP were significantly related to the concentrations of cTnI, and most obviously in the high-cTnI group. In subjects with no signs of CVD (cardiovascular disease), only levels of NT-proBNP related to cTnI, and with the highest NT-proBNP levels in the high-cTnI group (p<0.01). A multiple regression analysis showed that NT-proBNP was independently related to cTnI (p<0.001)., Conclusions: Measurement of cardiac troponins with highly sensitive assays identifies those at risk of premature CVD death who have hitherto remained unrecognized. The associated elevations of NT-proBNP in these participants support the fact that these elevations reflect ongoing pathological processes in the myocardium.

Background: The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly., Methods: We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index)., Results: During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit., Conclusions: Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors., (Copyright 2008 Massachusetts Medical Society.)

Objective: To determine the effect of new, persistent or reverted ischaemic ECG abnormalities at ages 50 and 70 years on the risk of subsequent cardiovascular disease., Design, Setting and Participants: A prospective community-based observational cohort of 50-year-old men in Sweden, followed for 32 years. 2322 men of age 50 years participated in 1970-3, and 1221 subjects were re-examined at the age of 70 years., Main Outcome Measures: Myocardial infarction (MI), cardiovascular mortality and overall mortality., Results: At 50 years of age, after adjusting for established conventional risk factors, T wave abnormalities, ST segment depression, major Q/QS pattern and ECG-left ventricular hypertrophy were all found to be independent risk factors for the main outcome measures during the 32 years of follow-up. When ECG variables were re-measured at 70 years of age, they were still found to be independent risk factors for the mortality outcomes, but lost in significance for prediction of MI. Regarding mortality, it was twice as dangerous to have persistent T wave abnormalities (HR 4.63; 95% CI 2.18 to 9.83) or ST segment depression (HR 5.66; 95% CI 1.77 to 18.1), as with new T wave abnormalities (HR 2.20; 95% CI 1.48 to 3.29) or ST segment depression (HR 2.55; 95% CI 1.74 to 3.75), developing between ages 50 and 70 years. The addition of "ECG indicating ischaemia" significantly increased the predictive power of the Framingham score (p<0.001)., Conclusions: It is worthwhile to obtain serial ECGs for proper risk assessment, since persistent ST-T abnormalities carried twice as high a risk for future mortality compared with new or reverted abnormalities.

Objectives: To explore whether the predictive power of mid-life ECG abnormalities and conventional cardiovascular risk factors for future stroke change over a 30-year follow-up period, and whether a repeated examination improves their predictive power., Design and Setting: Longitudinal population-based study., Participants: 2,322 men aged 50 years, with a follow-up period of 30 years. 1,221 subjects were re-examined at age 70 years, Main Outcome Measure: Risk for fatal and non-fatal stroke during three decades of follow-up. Investigations included resting ECG and traditional cardiovascular risk factors., Results: When measured at age 50 years, ST segment depression and T wave abnormalities, together with ECG-left ventricular hypertrophy, were of importance only during the first 20 years, but regained importance when re-measured at age 70 years. Blood pressure was a significant predictor for stroke over all three decades of follow-up. In elderly people only, there is evidence that apolipoprotein A1 may protect from future stroke., Conclusion: Mid-life values for blood pressure and ECG abnormalities retain their predictive value over long follow-up periods even though they improved in predictive power when re-measured in elderly people. Despite lower prevalence, ECG abnormalities had greater impact at age 50 years than at age 70 years. By contrast, apolipoprotein A1 was protective for future stroke only at age 70 years.

Objectives: To find out if the presence of the metabolic syndrome increases the risk of subsequent total and cardiovascular mortality, taking into account established risk factors for cardiovascular disease., Design: Prospective cohort study., Setting: General population., Participants: A community based sample of 2322 men followed since 1970 for a maximum of 32.7 years, investigated at ages 50 and 70., Main Outcome Measures: The relations of the metabolic syndrome defined by the national cholesterol education programme (NCEP) of the US National Heart, Lung, and Blood Institute or criteria of the World Health Organization (WHO) to subsequent total and cardiovascular mortality., Results: When adding the metabolic syndrome to models with established risk factors for cardiovascular disease (smoking, diabetes, hypertension, and serum cholesterol) at age 50, presence of the metabolic syndrome as defined in the NCEP significantly predicted total and cardiovascular mortality (Cox proportional hazard ratios 1.36, 95% confidence interval 1.17 to 1.58; and 1.59, 1.29 to 1.95, respectively). The metabolic syndrome added prognostic information to that of the established risk factors for cardiovascular disease (likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were obtained in a subsample without diabetes or manifest cardiovascular disease., Conclusions: In a large, community based sample of middle aged men, the presence of the metabolic syndrome according to the definition of the NCEP gave long term prognostic information regarding total and cardiovascular mortality if the status of established risk factors for cardiovascular disease was known. If confirmed this may indicate clinical value in diagnosing the metabolic syndrome.

We assessed blood pressure (BP) trends in patients with type 2 diabetes from a national diabetes register using three cross-sectional samples (aged 30-85 years) in 2005, 2007 and 2009, and in patients from 2005 followed individually until 2009. The prevalence of hypertension was 87% among all 180 369 patients in 2009, although lower in subgroups with ages 30-39, 40-49 and 50-59 years: 40%, 60% and 77%. In the three cross-sectional surveys, mean BP decreased (141/77-136/76 mmHg), uncontrolled BP≥ 140/90 mmHg decreased (58-46%), and antihypertensive drug treatment (AHT) increased (73-81%). Comparatively in 79 185 patients followed individually for 5 years, mean BP decreased (141/77-137/75 mmHg), uncontrolled BP ≥140/90 mmHg decreased (58-47%) and AHT increased (73-82%). Independent predictors of BP decrease were BMI decrease (stronger) and increase in AHT. AHT occurred among 81% of all patients in 2009. In 57 645 patients on AHT followed individually, mean BP decreased (143/77-138/75 mmHg) and uncontrolled BP ≥140/90 mmHg decreased (63-50%). Among 5164 patients with nephropathy on AHT followed individually, BP <130/80 mmHg increased (12-21%). In conclusion, BP control improved from 2005 to 2009, relative to BMI decrease and AHT increase, although still about half had BP ≥140/90 mmHg. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years. RESEARCH DESIGN AND METHODS -- A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007). RESULTS -- Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002- 0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with AIC 8-11.9% (mean 9.0), fully adjusted also for albuminuria. CONCLUSIONS -- This observational study of patients in modem everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Risk prediction models obtained in samples from the general population do not perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with use of A1C and clinical characteristics. RESEARCH DESIGN AND METHODS -- The study was based on 11,646 female and male patients, aged 18-70 years, from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up of 5.64 years. RESULTS -- This risk equation incorporates A1C, as in the UK Prospective Diabetes Study risk engine, and several clinical characteristics: onset age of diabetes, diabetes duration, sex, BMI, smoking, systolic blood pressure, and antihypertensive and lipid-reducing drugs. All predictors included were associated with the outcome (P < 0.0001, except for BMI P = 0.0016) with Cox regression analysis. Calibration was excellent when assessed by comparing observed and predicted risk. Discrimination was sufficient, with a receiver operator curve statistic of 0.70. Mean 5-year risk of CVD in ail patients was 12.0 ± 7.5%, whereas 54% of the patients had a 5-year risk ≥10%. CONCLUSIONS -- This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of new, persistent or reverted ischaemic ECG abnormalities at ages 50 and 70 years on the risk of subsequent cardiovascular disease. Design, setting and participants: A prospective community-based observational cohort of 50-year-old men in Sweden, followed for 32 years. 2322 men of age 50 years participated in 1970-3, and 1221 subjects were re-examined at the age of 70 years. Main outcome measures: Myocardial infarction (MI), cardiovascular mortality and overall mortality. Results: At 50 years of age, after adjusting for established conventional risk factors, T wave abnormalities, ST segment depression, major Q/QS pattern and ECG-left ventricular hypertrophy were all found to be independent risk factors for the main outcome measures during the 32 years of follow-up. When ECG variables were re-measured at 70 years of age, they were still found to be independent risk factors for the mortality outcomes, but lost in significance for prediction of MI. Regarding mortality, it was twice as dangerous to have persistent T wave abnormalities (HR 4.63; 95% CI 2.18 to 9.83) or ST segment depression (HR 5.66; 95% CI 1.77 to 18.1), as with new T wave abnormalities (HR 2.20; 95% CI 1.48 to 3.29) or ST segment depression (HR 2.55; 95% CI 1 .74 to 3.75), developing between ages 50 and 70 years. The addition of "ECG indicating ischaemia" significantly increased the predictive power of the Framingham score (p<0.001). Conclusions: It is worthwhile to obtain serial ECGs for proper risk assessment, since persistent ST-T abnormalities carried twice as high a risk for future mortality compared with new or reverted abnormalities. [ABSTRACT FROM AUTHOR]

Context Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. Objective To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. Design, Setting, and Participants The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (≥70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. Main Outcome Measure First hospitalization for heart failure. Results One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. Conclusions Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance. [ABSTRACT FROM AUTHOR]

Aims Assessing the association between BMI and risk of coronary heart disease (CHD), cardiovascular disease (CVD) and mortality in patients with type 2 diabetes, also with regard to higher or lower levels of the ratio triglycerides-to-HDL-cholesterol (TG:HDL). Methods 54,061 patients with BMI ≥ 18.5 kg/m 2 , mean age and duration 61.5 ± 8 and 6.9 ± 6 years, 59% males, 14% with CVD history, from the Swedish National Diabetes Register, followed for mean 4.8 years. Results Adjusting at Cox regression for non-BMI-linked (age, sex, smoking, CVD history) and BMI-linked (blood lipids, blood pressure, HbA1c, albuminuria) covariates, hazard ratios (HR) for fatal/nonfatal CHD and CVD were mainly increased with prominent obesity (BMI ≥ 35 kg/m 2 ), 1.19 ( p = 0.01) and 1.17 ( p = 0.009), compared to normal weight (BMI 18.5–24.9 kg/m 2 ), although increased also with obesity (BMI 30–34.9 kg/m 2 ), 1.34 and 1.30 ( p < 0.001), when adjusting only for non-BMI-linked covariates. Stratifying by 75th percentile of TG:HDL, with normal weight and TG:HDL < 1.9 as reference, obese and prominently obese with TG:HDL ≥ 1.9 had considerably increased HR around 1.7 for fatal/nonfatal CHD and 1.6 for CVD ( p < 0.001), while obese and prominently obese with TG:HDL < 1.9 only had HR 1.2–1.3 for CHD and CVD ( p 0.003–<0.01). Conclusion Obese T2D patients with high TG:HDL, associated with increased insulin resistance, had considerably increased risk of CHD and CVD. [ABSTRACT FROM AUTHOR]