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Abstract Background The increased risk of cardiovascular disease (CVD) in diabetic compared to non-diabetic subjects seems to decrease with age. Whether this age-related reduction applies to CVD risk factors, and whether it is limited to established diabetes mellitus (DM) or also applies to pre-diabetic conditions are not well known. Methods Using a cross-sectional design we compared the strength of the correlation between glucometabolic disturbances (by grouping), CVD risk factor burden and self-rated health, in two age groups: middle-aged (57-69 years) and older (70-86 years) subjects, (63% men), participating in the Malmö Preventive Project Re-examination Study (n = 18,238). Simple (unadjusted) logistic regression analysis was applied to estimate between-group differences and trends. Interaction analysis was applied to estimate differences between age groups. Results CVD risk factor burden and the proportion of subjects reporting poor self-rated health increased with increasing glucometabolic disturbance for men and women in both age groups (p-trend < 0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for older women than for older men (p-interaction = 0.002). The slope of the trend curve for poor self-rated health was significantly steeper for middle-aged than for older men (p-interaction = 0.005), while no difference was observed between the age groups among women (p-interaction = 0.97). Conclusions We found no reduction in risk factor accumulation with increasing glucometabolic disturbance between middle-aged and older subjects. Our results indicate life-long CVD risk factor clustering with increased glucometabolic disturbance, and suggest that previously observed age-related reduction in excess CVD risk for subjects with DM might be due to a survival bias. However, our observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.

Abstract Background Indications for implantable cardioverter defibrillator (ICD) implantation have expanded considerably in recent years, resulting in steadily growing numbers of ICD recipients worldwide. The aim of this study was to review the overall experience with ICDs in Iceland. Methods This was a retrospective single centre study set at the University Hospital in Iceland. Data on all ICD implantations in Iceland from the first implantation in 1992 till the end of 2002 was reviewed. Results Sixty-two patients (71% male) received an ICD during this period. There was an increase in the number of implants by year and the number of new implants in 2001 and 2002 amounted to 56 and 38 per million, respectively. The mean age at implantation was 58 (+/-14) years. Forty patients (65%) had coronary artery disease. The most common indications for ICD implantation were cardiac arrest, 32 (52%) and another 26 (42%) had experienced ventricular tachycardia without cardiac arrest. The most common adverse event was inappropriate shocks. Twenty-eight patients (45%) received therapy from their ICDs, with the majority receiving appropriate therapy. Of the thirteen patients deceased before or during the study period, no case of sudden arrhythmic death was observed. Conclusion This study shows that the experience with ICDs in Iceland is in most respects similar to other Western countries.

Aims: Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts., Methods and Results: A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF., Conclusion: In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI., Methods: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI., Results: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014)., Conclusions: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality., (© 2024. The Author(s).)

Background: Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs., Methods: The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation., Discussion: Optimizing cardiac rehabilitation centres' delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI., Trial Registration: ClinicalTrials.gov. Identifier: NCT05889416 . Registered 2023-03-23., (© 2024. The Author(s).)

Background A significant proportion of patients with ST-segment-elevation myocardial infarction (MI) have no standard modifiable cardiovascular risk factors (SMuRFs) and have unexpected worse 30-day outcomes compared with those with SMuRFs. The aim of this article is to examine outcomes of patients with non-ST-segment-elevation MI in the absence of SMuRFs. Methods and Results Presenting features, management, and outcomes of patients with non-ST-segment-elevation MI without SmuRFs (hypertension, diabetes, hypercholesterolemia, smoking) were compared with those with SmuRFs in the Swedish MI registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies; 2005-2018). Cox proportional hazard models were used. Out of 99 718 patients with non-ST-segment-elevation MI, 11 131 (11.2%) had no SMuRFs. Patients without SMuRFs had higher all-cause and cardiovascular mortality at 30 days (hazard ratio [HR], 1.20 [95% CI, 1.10-1.30], P <0.0001; and HR, 1.25 [95% CI, 1.13-1.38]), a difference that remained after adjustment for age and sex. SMuRF-less patients were less likely to receive secondary prevention statins (76% versus 82%); angiotensin-converting enzyme inhibitors/angiotensin receptor blockade (54% versus 72%); or β-blockers (81% versus 87%, P for all <0.0001), with lowest rates observed in women without SMuRFs. In patients who survived to 30 days, rates of all-cause and cardiovascular death were lower in patients without SMuRFs compared with those with risk factors, over 12 years. Conclusions One in 10 patients presenting with non-ST-segment-elevation MI present without traditional risk factors. The excess 30-day mortality rate in this group emphasizes the need for both improved population-based strategies for prevention of MI, as well as the need for equitable evidence-based treatment at the time of an MI.

Background: Oral lipid-lowering treatment (LLT) is the standard of care for patients with cardiovascular disease (CVD). However, insufficient treatment intensity and poor adherence can lead to suboptimal treatment benefit, rendering patients at increased risk of CVD., Aims: The objective of this study was to evaluate trends in LLT intensity and adherence in Sweden over time, and their association with major adverse cardiovascular events (MACE) after recent myocardial infarction (MI), and also to assess the impact of transition from secondary to primary care on intensity and adherence., Methods and Results: This retrospective observational cohort study used data from Swedish nationwide patient registers and included patients on LLT after an MI in the years 2010-2016 ( n = 50,298; mean age, 68 years; 69% men). LLT intensity was evaluated over time (overall, for 2010-2013 and for 2014-2016) as the proportion of patients prescribed low-, moderate-, and high-intensity LLT. Adherence was assessed as the proportion of days covered. A combined measure of intensity and adherence was also considered. Differences in treatment patterns and MACE were assessed. Initiation of high-intensity LLT increased over the two time periods studied (2010-2013, 32%; 2014-2016, 91%). Adherence varied by LLT intensity and was highest in patients receiving high-intensity LLT (>80%), especially during the first time period. Little change in treatment intensity or the combined measure of intensity and adherence was observed after transition to primary care. There was a significant association between the combined measure of intensity and adherence and MACE reduction (hazard ratio [95% confidence interval] per 10% increase in the combined measure: 0.84 [0.82-0.86]; P < 0.01)., Conclusion: The proportion of post-MI patients with high LLT intensity and adherence has increased in recent years, with little change after transfer from specialist to primary care. The combination of LLT intensity and adherence is important for preventing future cardiovascular events., Competing Interests: Maria K Svensson and Francesc Sorio were employed by Amgen when the study was conducted. Guillermo Villa is an employee and stockholder of Amgen. Margret Leósdóttir has received honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, MSD and Sanofi, investigator-initiated research grants from Amgen and Pfizer, and an honorarium from Amgen for work associated with this manuscript. Jonas Banefelt, Maria Lindh, and Alexander Rieem Dun are employed by Quantify Research, a contract research organization that provides consultancy services for the pharmaceutical industry. Anna Norhammar has received honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, MSD, and Boehringer Ingelheim, and an honorarium from Amgen for worktime associated with this manuscript., (© 2022 The Author(s). Published by Upsala Medical Society.)

Background: Cardiac rehabilitation is central in reducing mortality and morbidity after myocardial infarction. However, the fulfillment of guideline-recommended cardiac rehabilitation targets is unsatisfactory. eHealth offers new possibilities to improve clinical care., Objective: This study aims to assess the effect of a web-based application designed to support adherence to lifestyle advice and self-control of risk factors (intervention) in addition to center-based cardiac rehabilitation, compared with cardiac rehabilitation only (usual care)., Methods: All 150 patients participated in cardiac rehabilitation. Patients randomized to the intervention group (n=101) received access to the application for 25 weeks where information about lifestyle (eg, diet and physical activity), risk factors (eg, weight and blood pressure [BP]), and symptoms could be registered. The software provided feedback and lifestyle advice. The primary outcome was a change in submaximal exercise capacity (Watts [W]) between follow-up visits. Secondary outcomes included changes in modifiable risk factors between baseline and follow-up visits and uptake and adherence to the application. Regression analysis was used, adjusting for relevant baseline variables., Results: There was a nonsignificant trend toward a larger change in exercise capacity in the intervention group (n=66) compared with the usual care group (n=40; +14.4, SD 19.0 W, vs +10.3, SD 16.1 W; P=.22). Patients in the intervention group achieved significantly larger BP reduction compared with usual care patients at 2 weeks (systolic -27.7 vs -16.4 mm Hg; P=.006) and at 6 to 10 weeks (systolic -25.3 vs -16.4 mm Hg; P=.02, and diastolic -13.4 vs -9.1 mm Hg; P=.05). A healthy diet index score improved significantly more between baseline and the 2-week follow-up in the intervention group (+2.3 vs +1.4 points; P=.05), mostly owing to an increase in the consumption of fish and fruit. At 6 to 10 weeks, 64% (14/22) versus 46% (5/11) of smokers in the intervention versus usual care groups had quit smoking, and at 12 to 14 months, the respective percentages were 55% (12/22) versus 36% (4/11). However, the number of smokers in the study was low (33/149, 21.9%), and the differences were nonsignificant. Attendance in cardiac rehabilitation was high, with 96% (96/100) of patients in the intervention group and 98% (48/49) of patients receiving usual care only attending 12- to 14-month follow-up. Uptake (logging data in the application at least once) was 86.1% (87/101). Adherence (logging data at least twice weekly) was 91% (79/87) in week 1 and 56% (49/87) in week 25., Conclusions: Complementing cardiac rehabilitation with a web-based application improved BP and dietary habits during the first months after myocardial infarction. A nonsignificant tendency toward better exercise capacity and higher smoking cessation rates was observed. Although the study group was small, these positive trends support further development of eHealth in cardiac rehabilitation., Trial Registration: ClinicalTrials.gov NCT03260582; https://clinicaltrials.gov/ct2/show/NCT03260582., International Registered Report Identifier (irrid): RR2-10.1186/s13063-018-3118-1., (©Halldóra Ögmundsdóttir Michelsen, Ingela Sjölin, Maria Bäck, Manuel Gonzalez Garcia, Anneli Olsson, Camilla Sandberg, Alexandru Schiopu, Margrét Leósdóttir. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.03.2022.)

Background: In cardiovascular disease, prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, hypercholesterolaemia, and smoking) are crucial; however, myocardial infarction in the absence of SMuRFs is not infrequent. The outcomes of individuals without SMuRFs are not well known., Methods: We retrospectively analysed adult patients with first-presentation ST-elevation myocardial infarction (STEMI) using data from the Swedish myocardial infarction registry SWEDEHEART. Clinical characteristics and outcomes of adult patients (age ≥18 years) with and without SMuRFs were examined overall and by sex. Patients with a known history of coronary artery disease were excluded. The primary outcome was all-cause mortality at 30 days after STEMI presentation. Secondary outcomes included cardiovascular mortality, heart failure, and myocardial infarction at30 days. Endpoints were also examined up to discharge, and to the end of a 12-year follow-up. Multivariable logistic regression models were used to compare in-hospital mortality, and Cox-proportional hazard models and Kaplan-Meier analysis for long-term outcomes., Findings: Between Jan 1, 2005, and May 25, 2018, 9228 (14·9%) of 62 048 patients with STEMI had no SMuRFs reaching diagnostic thresholds. Median age was similar between patients with SMuRFs and patients without SMuRFs (68 years [IQR 59-78]) vs 69 years [60-78], p<0·0001). SMuRF-less patients had a similar rate of percutaneous coronary intervention to those with at least one modifiable risk factor, but were significantly less likely to receive statins, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockade (ARB), or β-blockers at discharge. By 30 days after presentation, all-cause mortality was significantly higher in SMuRF-less patients (hazard ratio 1·47 [95% CI 1·37-1·57], p<0·0001). SMuRF-less women had the highest 30-day mortality (381 [17·6%] of 2164), followed by women with SMuRFs (2032 [11·1%] of 18 220), SMuRF-less men (660 [9·3%] of 7064), and men with SMuRFs (2117 [6·1%] of 34 600). The increased risk of 30-day all-cause mortality in SMuRF-less patients remained significant after adjusting for age, sex, left ventricular ejection fraction, creatinine, and blood pressure, but was attenuated on inclusion of pharmacotherapy prescription (ACEI or ARB, β-blocker, or statin) at discharge. Additionally, SMuRF-less patients had a significantly higher rate of in-hospital all-cause mortality than patients with one or more SMuRF (883 [9·6%] vs 3411 [6·5%], p<0·0001). Myocardial infarction and heart failure at 30 days were lower in SMuRF-less patients. All-cause mortality remained increased in the SMuRF-less group for more than 8 years in men and up to the 12-year endpoint in women., Interpretation: Individuals who present with STEMI in the absence of SMuRFs have a significantly increased risk of all-cause mortality, compared with those with at least one SMuRF, which was particularly evident in women. The increased early mortality rates are attenuated after adjustment for use of guideline-indicated treatments, highlighting the need for evidence-based pharmacotherapy during the immediate post-infarct period irrespective of perceived low risk., Funding: Swedish Heart and Lung Foundation, National Health and Medical Research Council (Australia)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality., Methods and Results: Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide., Conclusions: In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

It is unclear whether 12-lead ECG employing standard criteria for left ventricular hypertrophy (LVH) provides similar information with respect to long-term cardiovascular risk as echocardiography. The authors performed a retrospective cohort study of 1376 individuals without cardiovascular disease, who underwent ECG (LVH defined using the Sokolow-Lyon voltage combination (>35 mm) or the Cornell voltage-duration product (>2440 mm × ms)) and echocardiography (LVH defined as LV mass index (LVMI) >95 g/m 2 for women and >115 g/m 2 for men). The prognostic ability of LVH was assessed in Cox regression models adjusted for age, sex, smoking, systolic blood pressure, total cholesterol, antihypertensive medication, and fasting glucose. The primary end point was the composite of coronary events, heart failure, stroke, or death. The main secondary end point was heart failure or cardiovascular death. Median age was 67 (range 56-79) years, 68% were male. Eleven percent had ECG-defined LVH, 17% had echocardiographic LVH. Over median 8.5 years, 29% experienced a primary event. Event rates were 29%/35% for persons without/with ECG-defined LVH and 27%/39% for those without/with echocardiographic LVH. The Sokolow-Lyon combination, Cornell product, and ECG-defined LVH did not significantly predict the primary end point (P ≥ .05), but ECG-defined LVH predicted heart failure or cardiovascular death (adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.13-3.08); P = .02). Conversely, LVMI was a significant, independent predictor of the primary end point (adjusted HR, 1.87, 95% CI, 1.13-3.10; P = .01), as was echocardiographic LVH (adjusted HR, 1.27, 95% CI, 1.01-1.61; P = .04). Echocardiographic LVH may be a better predictor of long-term cardiovascular risk than ECG-defined LVH in middle-aged and older individuals., (© 2020 Wiley Periodicals LLC.)

Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.

Objective: To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality., Design: Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992., Methods: 4934 men without known diabetes and cardiovascular disease, who had blood glucose (BG) measured at 0, 20, 40, 60, 90 and 120 min during an OGTT (30 g glucose per m 2 body surface area), were followed for 27 years. Data on cardiovascular events and death were obtained through national and local registries. Predictive capabilities of fasting BG (FBG) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrell's concordance index (C-index) and integrated discrimination improvement (IDI)., Results: Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascular events or death. Conversely, 1-h postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death (HR: 1.09, 95% CI: 1.01-1.17, P  = 0.02) and all-cause mortality (HR: 1.10, 95% CI: 1.05-1.16, P  < 0.0001) after adjusting for various traditional risk factors. Clinical risk factors with added 1-h postload BG performed better than clinical risk factors alone, in predicting cardiovascular death (likelihood-ratio test, P  = 0.02) and all-cause mortality (likelihood-ratio test, P  = 0.0001; significant IDI, P  = 0.0003)., Conclusion: Among men without known diabetes, addition of 1-h BG, but not FBG or 2-h BG, to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality., (© 2018 European Society of Endocrinology.)

Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1 N-terminal propeptide (P1NP), in predicting incident cardiovascular events and mortality among asymptomatic individuals from the general population, beyond traditional risk factors, including fasting glucose and renal function (cystatin C), medication use, and echocardiographic measures. Methods and results Prospective population-based cohort study of 1324 subjects without a previous cardiovascular event, who underwent baseline echocardiography and biomarker assessment between 2002 and 2006. The clinical endpoint was the composite of myocardial infarction, invasively treated stable/unstable ischemic heart disease, heart failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60-70) years, and 413 (31%) were female. During median 8.6 (interquartile range: 8.1-9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography ( p < 0.05 for all). Separate addition of NT-proBNP and GDF-15 to traditional risk factors, medications, and echocardiographic measurements provided significant improvements in discriminative ability (NT-proBNP: C-index 0.714 vs. 0.703, p = 0.03; GDF-15: C-index 0.721 vs. 0.703, p = 0.02). Both biomarkers remained significant predictors of outcome upon inclusion in the same model ( p < 0.05 for both). Conclusions NT-proBNP and GDF-15 each enhance prognostication beyond traditional risk factors, glucose levels, renal function, and echocardiography in individuals without known cardiovascular disease.

Aims: To examine whether baseline fasting plasma glucose (FPG) modifies the prognostic role of left ventricular (LV) mass, geometric pattern, and diastolic function, for prediction of cardiovascular morbidity and mortality., Methods: Population-based cohort study comprising of 1047 men and 456 women with preserved ejection fraction, included between 2002 and 2006, who underwent echocardiography based on groups defined by FPG, measured prior to echocardiography. The clinical endpoint was the composite of cardiovascular events and all-cause mortality, assessed through national and local registries. Cox proportional-hazards regression with interaction analysis was used to evaluate the risk associated with FPG and LV structure and function., Results: Median age was 67years, and 31% had impaired fasting glucose, 31% diabetes, 17% LV hypertrophy, and 40% diastolic dysfunction. During a median follow-up duration of 8.3years, 449 composite events occurred. FPG (hazard ratio (HR), 1.09 (95% confidence interval (CI): 1.05-1.13), P<0.001) and several markers of LV structure and function, including LV mass index (HR, 1.10 (95% CI: 1.06-1.15), P<0.001) and E/é (HR, 1.08 (95% CI 1.05-1.10), P<0.001) were associated with an increased risk of events. In the subgroup of 678 individuals without previous cardiovascular disease, who did not receive cardiovascular, anti-diabetic, or lipid-lowering medication, FPG significantly interacted with the association between concentric LV hypertrophy and event risk (P<0.001), and with the association between diastolic dysfunction and event risk (P=0.02), including grade 2 or 3 dysfunction (P=0.04)., Conclusions: Echocardiographic abnormalities were more strongly associated with an adverse prognosis among subjects with impaired fasting glucose or diabetes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population., Methods: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography., Results: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography., Conclusion: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

Objective: To examine the impact of follow-up duration on the incremental prognostic yield of a baseline oral glucose tolerance test (OGTT) for predicting type 2 diabetes and to assess the discrimination ability of blood glucose (BG) obtained at different time points during OGTT., Design: A prospective, population-based cohort study (Malmö Preventive Project) with inclusion of subjects from 1974 to 1992., Methods: A total of 5256 men without diabetes, who had BG measured at 0, 20, 40, 60, 90, and 120 min during OGTT (30 g/m2 glucose), were followed for 30 years. Incident type 2 diabetes was recorded using registries. The performance of OGTT added to a clinical prediction model (age, body mass index (BMI), diastolic blood pressure, fasting BG, triglycerides, and family history of diabetes) was assessed using Harrell's concordance index (C-index) and integrated discrimination improvement (IDI)., Results: Median age was 48 years, mean BMI 24.9 kg/m2, and mean fasting BG 4.7 mmol/L. Models with added post-load BG performed better than the clinical model (C-index: P = 0.08 for BG at 120 min at 5 years, otherwise P ≤ 0.045; IDI: P ≥ 0.06 for BG at 60 and 90 min at 5 years, otherwise P ≤ 0.01). With a longer follow-up duration, C-index decreased, and the C-index increase associated with OGTT was attenuated. Models including BG at 60 or 90 min performed significantly better than the model with BG at 120 min, evident beyond follow-up of 10 and 5 years, respectively., Conclusions: OGTT provided incremental prognostic yield for type 2 diabetes prediction. BG measured at 60 or 90 min provided better discrimination than BG at 120 min., (© 2016 European Society of Endocrinology.)

Background: To examine whether lower insulin sensitivity as determined by homeostatic model assessment (HOMA-%S) was associated with increased left ventricular mass (LVM) and presence of LV diastolic dysfunction at long-term follow-up, independently of body mass index (BMI), in middle-aged, otherwise healthy males., Methods: Prospective population-based cohort study with a median (IQR) follow-up time of 28 (27-28) years, in which traditional cardiovascular risk factors, including HOMA-%S and BMI, were assessed at baseline, and echocardiographic determination of LVM and LV diastolic function was performed at follow-up. Associations between risk factors and echocardiographic variables were tested using multivariable linear and binary logistic regression., Results: The study population comprised 247 men with a median (IQR) age of 47 (47-48) years. Mean (SD) BMI was 25.1 +/- 3.0 kg/m(2), and median (IQR) HOMA-%S was 113.0 (68.3-284.6). Subjects with low insulin sensitivity (lowest HOMA-%S quartile (Q1)) had significantly greater BMI, fasting plasma insulin, and higher fasting blood glucose (FBG) (p <0.02 for all). BMI and HOMA-%S were significantly correlated (r = -0.383, p <0.0001). At follow-up, mean (SD) LVM and LVMI were 202 +/- 61 g and 103 +/- 31 g/m(2), respectively, whereas median (IQR) E/é was 10 (8-12). Moreover, 36 % had grade 2 or 3 diastolic dysfunction. In multivariable analyses, greater BMI, but not low insulin sensitivity was independently associated with later detection of increased LVM and diastolic dysfunction., Conclusion: Greater baseline BMI, but not lower insulin sensitivity was independently associated with greater LVM and diastolic dysfunction at long-term follow-up.

Objective: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography., Methods: Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH was defined by either Cornell voltage-duration product (CP) or Sokolow-Lyon voltage combination (SL), and univariate and multivariable regressions were performed in search of explanatory factors for the presence of LVH and the values of CP and SL., Results: Of the 1759 subjects included, 1007 had a history of cardiovascular disease and/or medical treatment, while 752 subjects appeared to be healthy. We found an independent association between FPG and LVH (odds ratio 1.152, p = 0.042] as well as continuous CP (beta = 0.126, p = 0.007) in healthy men. As expected, we found an association between systolic blood pressure and LVH (odds ratio 1.020, p < 0.001) among healthy subjects, but only in subjects with FPG < 6 mmol/l (p = 0.04 for interaction)., Conclusions: We found an independent association between FPG and LVH in healthy men, and no potentiating effect by FPG on the impact of hypertension.

Aims: In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown., Methods and Results: We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P<0.05) and fractional shortening (12.2%, P<0.05) were declined. The adverse effects of WDR12 gene delivery on cardiac function were associated with decreased cellular proliferation, activation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein (HSP) 27 pathway, and increased protein levels of Block of proliferation 1 (BOP1), essential for ribosome biogenesis. Post-infarction WDR12 gene delivery decreased E/A ratio (32%, P<0.05) suggesting worsening of diastolic function. In human subjects, MI associated WDR12 allele was associated significantly with diastolic dysfunction and left atrial size., Conclusions: WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.

Aims: To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects., Methods and Results: We tested cross-sectional associations between echocardiographically determined averaged E/é ratio/diastolic function, LVMI, cardiovascular risk factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Median E/é was significantly higher among subjects with diabetes than those without (8 vs. 7; p = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs. 16%; p = 0.02). E/é and diastolic function were significantly associated with LVMI (p ≤ 0.002), but not FPG category, on multivariable analysis. However, interaction analyses revealed that increasing LVMI was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG > 6 mmol/L (β=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing systolic blood pressure was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG ≤ 6.9 mmol/L (β = 0.005 for NFG and 0.003 for IFG vs. -0.001 for DM; p=0.001)., Conclusion: Diastolic dysfunction was significantly more prevalent among patients with DM than those without. The importance of LVMI increased, but the importance of systolic blood pressure decreased with higher FPG category., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)