Nonfatal Ischemic Heart Disease Research Articles

Abstract 2085: Study Of The Relationship Between Brachial Artery Volumetric Elastic Modulus And Estimated Brachial Artery Lumenal Area And Prognosis In Hemodialysis Patients

Objectives: Patients with hemodialysis (HD) have a higher incidence of CVD and worse prognosis than non-dialysis patients. Recently, a new device can measure novel parameters of arterial stiffness such as brachial artery volume elastic modulus (VE) and estimated brachial artery lumen cross-sectional area (eA) in a minimally invasive and simplified manner. Using this device, we investigated the relationship between these parameters and prognosis in HD patients. Methods and Results: This was a multicenter, prospective, observational study. A total of 246 patients on maintenance dialysis at six maintenance dialysis centers were registered. They were 158 men (64%), mean age 69±13 years, mean years on dialysis 5.8±6.2 years, BP 143±23/78±13 mmHg, Hb 11.5±6.9 g/dL, Alb 3.5±0.4 g/dL, corrected-Ca 9.2±0.8 mg/dL, P 5.4±2.7 mg/dL, iPTH 164±180 pg/mL. 125 patients (51%) had diabetes mellitus and 122 patients (50%) were current and past smokers. 51 (20%) had a history of ischemic heart disease, 23 (9%) had a history of symptomatic stroke, and 45 (18%) had a history of peripheral arterial disease. VE and eA were measured in the non-shunt limb during dialysis. Outcomes were death and MACE (non-fatal ischemic heart disease, symptomatic stroke, and PAD requiring intervention). 44 patients died, 20 had ischemic heart disease, 6 had symptomatic stroke, and 6 had PAD during the 3-year observation period. Patients were divided into 2 groups based on the median VE value and analyzed using the Kaplan-Meier method for death plus MACE, death, and MACE each, but no significant differences were found. eA was also examined in the same way, but no significant differences were found. Further, patients were divided into 4 groups based on the VE and eA values (high&high, high&low, low&high, and low&low for VE&eA, respectively) and were studied in the same fashion, the high&low and low&high groups had significantly higher incidence of death plus MACE (log-rank p=0.0184) and MACE (log-rank p=0.0310) than the high&high and low&low groups. Conclusion: In HD patients, we found that the combined assessment of VE and eA was significantly associated with their prognosis, suggesting that these parameters may be clinically useful.

A comparative study of cardiovascular risk stratification methods in type 1 diabetes mellitus patients

The Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease, ischemic stroke, heart failure, and peripheral arterial disease in type 1 diabetes mellitus(T1DM).The current study investigated the agreement between ST1RE and the Brazilian Society for Endocrinology and Metabology (SBEM) classification. Participants were included in the study if diagnosed with T1DM and had at least one outpatient visit in 2021. Patients with established cardiovascular disease and chronic kidney disease on dialysis were excluded. Clinical parameters were obtained from medical records, such as age, body mass index (BMI), blood pressure, physical activity, current smoking, microvascular target organ damage, levels of low-density lipoprotein cholesterol, creatinine, glycated hemoglobin (HbA1c), and albuminuria.Overall, 92 patients (38 males and 53 females) with an age median (P25; P75) of 33 years (25.5;42.5), BMI of 24.8 + 4.1 kg/m2, and duration of diabetes (mean ± SD) of 23.4 + 9.5 years were evaluated. There were no differences considering the gender for most analyzed variables, but a higher proportion of women exhibited microvascular complications such as microalbuminuria, macroalbuminuria, and retinopathy. Our results show a weak agreement in the 10-year cardiovascular risk estimation between SBEM and ST1RE classifications. According to SBEM criteria, 72.8% of patients were considered high-risk, while only 15.2% of patients received the same classification using ST1RE. The dissimilarities between these two classifications were also evident when age and gender factors were compared. While 60% of patients under 35 years were classified as high risk according to SBEM criteria, only 1.8% received this stratification risk in the ST1RE classification.The results indicate a low agreement between the 10-year cardiovascular event risk classification by SBEM and the classification by ST1RE for type 1 diabetes patients without established cardiovascular disease.

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

New Therapeutic Options for Type 2 Diabetes Mellitus and Their Impact Against Ischemic Heart Disease.

Type 2 diabetes mellitus (T2DM) greatly increases risk for cardiovascular disease, including ischemic heart disease and myocardial infarction. With the completion of several cardiovascular outcomes trials (CVOTs) for new glucose-lowering therapies, including the sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists, we now have strong evidence alluding to the cardioprotective nature of these agents in people with T2DM. These agents have frequently been observed to reduce rates for 3-point major adverse cardiovascular events, which encompass death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Herein we will provide an overview on whether reductions in nonfatal myocardial infarction and ischemic heart disease status are a key component of the improved cardiovascular outcomes in people with T2DM treated with either SGLT2 inhibitors or GLP-1R agonists. Observations from preclinical studies will be compared to their clinical counterparts, while being further interrogated to define potential mechanisms that may account for SGLT2 inhibitor or GLP-1R agonist-induced cardioprotection against ischemic heart disease. A better understanding of the role these agents have in impacting the progression of ischemic heart disease in individuals with T2DM will have a substantial impact in our management of this patient population.

The Importance of Echocardiography Assessment in Coronary Patients Subject to Cardiovascular Recovery Programs

Abstract Cardiovascular diseases cause approximately one-third of deaths worldwide and an increasing number of individuals with non-fatal ischemic heart disease live with chronic disabilities and impaired quality of life. Cardiac rehabilitation is designed to limit the physiological and psychological effects of cardiac illness, reduce the risk for sudden death or re-infarction, control cardiac symptoms and enhance the psychosocial and vocational status of selected patients. The study group included a group of 78 patients who had a coronary event no more than 3 months ago and who are included in cardio-vascular recovery programs. The patients were echocardiographic evaluated at the first admission and later at 6 months. The evolution of the patients was a favorable one, being objectified an increase of both the ejection fraction of the left ventricle, as well as an improvement of MAPSE and TAPSE.

Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

SummaryBackgroundThe effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.MethodsWe did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.FindingsWe included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group.InterpretationPharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines.FundingBritish Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis

SummaryBackgroundThe effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.MethodsWe did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat.FindingsData for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4·15 years' follow-up (Q1–Q3 2·97–4·96), 42 324 participants (12·3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) and 36·0 (95% CI 35·3–36·7), in the comparator and intervention groups, respectively. Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89–0·94 for partipants without previous cardiovascular disease and 0·89, 0·86–0·92, for those with previous cardiovascular disease. In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories.InterpretationIn this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself.FundingBritish Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Pre-eclampsia and long-term health outcomes for mother and infant: an umbrella review.

Pre-eclampsia is a pregnancy-associated condition with complex disease mechanisms and a risk factor for various long-term health outcomes for the mother and infant. To summarise evidence on the association of pre-eclampsia with long-term health outcomes arising in women and/or infants. PubMed, EMBASE, Scopus and ISI Web of Science were searched from inception to July 2020. Systematic reviews and meta-analyses examining associations between pre-eclampsia and long-term health outcomes in women and their infants. Data were extracted by two independent reviewers. We re-estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, any evidence of small-study effects and excess significance bias. Twenty-one articles were included (90 associations). Seventy-nine associations had nominally statistically significant findings (P<0.05). Sixty-five associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in seven and two associations, respectively. Nine associations: cerebrovascular disease (cohort studies), cerebrovascular disease (overall), cardiac disease (cohort studies), dyslipidaemia (all studies), risk of death (late-onset pre-eclampsia), fatal and non-fatal ischaemic heart disease, cardiovascular mortality (cohort studies), any diabetes or use of diabetic medication (unadjusted), and attention deficit/hyperactivity disorder (ADHD) (adjusted) were supported with robust evidence. Many of the meta-analyses in this research field have caveats casting doubts on their validity. Current evidence suggests an increased risk for women to develop cardiovascular-related diseases, diabetes and dyslipidaemia after pre-eclampsia, while offspring exposed to pre-eclampsia are at higher risk for ADHD. Cardiovascular and cerebrovascular diseases were supported with convincing evidence for long-term health outcomes after pre-eclampsia.

The WHO/ILO report on long working hours and ischaemic heart disease – Conclusions are not supported by the evidence

Working hours is a ubiquitous exposure given that most adults are employed, and one that is modifiable via legislative change if not always through individual-level choice. According to a recent report from the World Health Organization (WHO) and International Labour Organization (ILO), there is currently sufficient evidence to conclude that long working hours (i.e., ≥55 h per week) elevate the risk of fatal and non-fatal ischaemic heart disease to a clinically meaningful extent. After assessing the data used by the ILO/WHO, we feel that the expert group has not correctly applied their own framework for assessing the strength of the evidence. In the meta-analysis of observational studies in the report, the association between long working hours and incident heart disease appeared stronger in lower quality cohort studies with a high risk of bias (minimally-adjusted hazard ratio 1.20, 95% CI 1.01–1.41, compared to standard 35–40 weekly hours) than in the superior-quality studies with a lower risk of bias for which the estimate was not significantly different from the null (1.08, 95% CI 0.93–1.25). There was also marked effect modification, such that there was no increase in ischaemic heart disease for those working long hours in high socioeconomic status occupations, a finding also reported in analyses of a recent census-based cohort study which was not included in the report. Our meta-analysis of all these studies confirm that the findings are not consistent but differ between subgroups and that the summary age- and sex-adjusted hazard ratio for long working hours in high socioeconomic status occupations does not support excess risk: 0.85, 95% CI 0.63–1.13 (Pinteraction = 0.005, total N = 451,982). For these and other reasons detailed in this commentary, we advance a more cautious interpretation of the existing evidence. The conclusions should be restricted to low socioeconomic status occupations only and more research is still needed to confirm or refute harmfulness and determine clinical relevance.

Risk factors for cardiovascular disease in rural South India: cohort study

Background and objectivesCardiovascular diseases (CVD) accounted for one-third of the deaths in India. We conducted a cohort study to estimate the incidence of CVD and the association of established risk...

Costs and Length of Stay of Hospitalizations due to Diabetes-Related Complications.

Background Diabetes mellitus (DM) has become a significant worldwide public health problem and economic burden because a great proportion of healthcare costs has been spent on the treatment of DM and its related complications. The aim of this study was to examine the costs and length of stay (LoS) of hospitalizations due to diabetes-related complications in Taiwan. Methods This study is a retrospective claim database analysis using the Longitudinal Cohort of Diabetes Patients, with 2012 used as the base year. The hospitalization costs and LoS per admission were estimated for each complication of interest using data from the LHDB 2004 to 2012 cohorts. The presence of eight DM-related complications were identified using the ICD-9-CM codes and procedure codes. ANOVA was used to examine the relationships of diabetes duration with the LoS and costs of the complications. Results A total of 27,473 DM patients who were hospitalized in 2012 due to one of the examined DM-related complications were identified. The most common complications that caused the hospitalizations were nonfatal stroke (34.7%) and nonfatal ischemic heart disease (IHD) (28.7%). Amputation was the complication with the longest hospital stay, with a mean ± SD of 21.6 ± 14.1 days, followed by nonfatal stroke (13.6 ± 11.3), ulcer (12.7 ± 11.8), and fatal IHD (12.2 ± 13.6). The complications with the greatest hospitalization cost were fatal IHD (mean = TWD 306,209.8; median = TWD 221,417.0; 1TWD = 0.034USD) and fatal myocardial infarction (mean = TWD 272,840.1; median = TWD 174,008). Conclusions This study indicates that DM-related complications are associated with significant hospital LoS and costs. The study results could be useful for economic evaluations of diabetes treatments and the estimation of the overall economic impact of diabetes.

General health checks in adults for reducing morbidity and mortality from disease.

General health checks are common elements of health care in some countries. They aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used individual screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is therefore important to assess whether general health checks do more good than harm. This is the first update of the review published in 2012. To quantify the benefits and harms of general health checks. We searched CENTRAL, MEDLINE, Embase, two other databases and two trials registers on 31 January 2018. Two review authors independently screened titles and abstracts, assessed papers for eligibility and read reference lists. One review author used citation tracking (Web of Knowledge) and asked trial authors about additional studies. We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening for more than one disease or risk factor in more than one organ system. Two review authors independently extracted data and assessed the risk of bias in the trials. We contacted trial authors for additional outcomes or trial details when necessary. When possible, we analysed the results with a random-effects model meta-analysis; otherwise, we did a narrative synthesis. We included 17 trials, 15 of which reported outcome data (251,891 participants). Risk of bias was generally low for our primary outcomes. Health checks have little or no effect on total mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.97 to 1.03; 11 trials; 233,298 participants and 21,535 deaths; high-certainty evidence, I2 = 0%), or cancer mortality (RR 1.01, 95% CI 0.92 to 1.12; 8 trials; 139,290 participants and 3663 deaths; high-certainty evidence, I2 = 33%), and probably have little or no effect on cardiovascular mortality (RR 1.05, 95% CI 0.94 to 1.16; 9 trials; 170,227 participants and 6237 deaths; moderate-certainty evidence; I2 = 65%). Health checks have little or no effect on fatal and non-fatal ischaemic heart disease (RR 0.98, 95% CI 0.94 to 1.03; 4 trials; 164,881 persons, 10,325 events; high-certainty evidence; I2 = 11%), and probably have little or no effect on fatal and non-fatal stroke (RR 1.05 95% CI 0.95 to 1.17; 3 trials; 107,421 persons, 4543 events; moderate-certainty evidence, I2 = 53%). General health checks are unlikely to be beneficial.

Health Care Costs Associated With Incident Complications in Patients With Type 2 Diabetes in Germany.

The aim of this study is to provide reliable regression-based estimates of costs associated with different type 2 diabetes complications. We used nationwide statutory health insurance (SHI) data from 316,220 patients with type 2 diabetes. Costs for inpatient and outpatient care, pharmaceuticals, rehabilitation, and nonmedical aids and appliances were assessed in the years 2013-2015. Quarterly observations are available for each year. We estimated costs (in 2015 euro) for complications using a generalized estimating equations model with a normal distribution adjusted for age, sex, occurrence of different complications, and history of complications at baseline, 2012. Two- and threefold interactions were included in an extended model. The base case model estimated total costs in the quarter of event for the example of a 60- to 69-year-old man as follows: diabetic foot €1,293, amputation €14,284, retinopathy €671, blindness €2,933, nephropathy €3,353, end-stage renal disease (ESRD) €22,691, nonfatal stroke €9,769, fatal stroke €11,176, nonfatal myocardial infarction (MI)/cardiac arrest (CA) €8,035, fatal MI/CA €8,700, nonfatal ischemic heart disease (IHD) €6,548, fatal IHD €20,942, chronic heart failure €3,912, and angina pectoris €2,695. In the subsequent quarters, costs ranged from €681 for retinopathy to €6,130 for ESRD. Type 2 diabetes complications have a significant impact on total health care costs in the SHI system, not only in the quarter of event but also in subsequent years. Men and women from different age-groups differ in their costs for complications. Our comprehensive estimates may support the parametrization of diabetes models and help clinicians and policy makers to quantify the economic burden of diabetes complications in the context of new prevention and treatment programs.

Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults

Aims/hypothesisHealth check programmes for chronic disease have been introduced in a number of countries. However, there are few trials assessing the benefits and harms of these screening programmes at the population level. In a post hoc analysis, we evaluated the effect of population-based screening for type 2 diabetes and cardiovascular risk factors on mortality rates and cardiovascular events.MethodsThis register-based, non-randomised, controlled trial included men and women aged 40–69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk score questionnaire. Individuals at moderate-to-high risk were invited to visit their GP for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other general practices in Denmark constituted the retrospectively constructed no-screening (control) group. Outcomes were mortality rate and cardiovascular events (cardiovascular disease death, non-fatal ischaemic heart disease or stroke). The analysis was performed according to the intention-to-screen principle.ResultsAmong the screening group, 27,177 (18%) individuals attended for assessment of diabetes status and cardiovascular risk. Of these, 1,533 were diagnosed with diabetes. During a median follow-up of 9.5 years, there were 11,826 deaths in the screening group and 141,719 in the no-screening group (HR 0.99 [95% CI 0.96, 1.02], p = 0.66). There were 17,941 cardiovascular events in the screening group and 208,476 in the no-screening group (HR 0.99 [0.96, 1.02], p = 0.49).Conclusions/interpretationA population-based stepwise screening programme for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in rate of mortality or cardiovascular events between 2001 and 2012.

Effects of invitation to participate in health surveys on the incidence of cardiovascular disease: a randomized general population study.

The effects of health checks on reducing cardiovascular disease morbidity and mortality in the general population have been questioned. There are few randomized studies with long-term follow-up. We used a cohort randomly selected from a general population as a randomized trial to study the effect of repeated general health checks on the 30-year incidence of ischaemic heart disease (IHD), stroke and all-cause mortality. The study included all persons ( n = 17 845) aged 30, 40, 50 and 60 years living in 11 municipalities in Copenhagen, the capital of Denmark. An age- and gender-stratified random sample ( n = 4789) was invited to up to three health checks, from 1982 to 1994 (intervention group). The remaining 12994 persons were defined as the control group. Complete follow-up on mortality, emigration and fatal and non-fatal IHD and stroke until 31 December 2012 was obtained by linkage to registries. There were 3209 and 2190 incident cases of IHD and stroke, respectively, and a total of 6432 deaths during follow-up (mean = 25.2 years). The hazard ratios (HRs) (95% confidence intervals, CIs) for persons in the intervention group versus persons in the control group were as follows: IHD (HR: 0.99, 95% CI: 0.92, 1.07), stroke (HR: 1.14, 95% CI: 1.04, 1.25) and all-cause mortality (HR: 1.03, 95% CI: 0.98, 1.09). Repeated general health checks offered to the general population had no beneficial effects on the development of IHD, stroke or all-cause mortality during 30 years of follow-up. An increased incidence of stroke was observed in the group offered health checks.

Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular disease in adult patients with type 1 diabetes

BackgroundRecent studies suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of cardiovascular disease (CVD) in type 1 diabetes. We assessed whether NAFLD also predicts the risk of incident CVD events in type 1 diabetic adults. MethodsWe studied a retrospective cohort of 286 type 1 diabetic outpatients (mean age 43±14years; median duration of diabetes 17 [10–30] years) without secondary causes of chronic liver diseases, who were followed for a mean period of 5.3years for the occurrence of incident CVD events (a combined endpoint inclusive of nonfatal ischemic heart disease, nonfatal ischemic stroke or coronary/peripheral artery revascularizations). NAFLD was diagnosed by ultrasonography. ResultsOverall, 150 patients (52.4%) had NAFLD at baseline. During a mean follow-up of 5.3±2.1years, 28 patients developed incident CVD events. Patients with NAFLD had a higher incidence of CVD events than those without NAFLD (17.3% vs. 1.5%, p<0.001). NAFLD was associated with an increased risk of CVD events (hazard ratio [HR] 8.16, 95% confidence interval [CI] 1.9–35.1, p<0.005). Adjustments for age, sex, body mass index, smoking, diabetes duration, hemoglobin A1c, dyslipidemia, hypertension, chronic kidney disease, prior ischemic heart disease and serum gamma-glutamyltransferase levels did not appreciably attenuate the association between NAFLD and incident CVD (adjusted-HR 6.73, 95% CI 1.2–38.1, p=0.031). ConclusionsThis is the first observational study to demonstrate that NAFLD is associated with an increased risk of incident CVD events in type 1 diabetic adults, independently of established CVD risk factors and diabetes-related variables.

Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis.

Objective The purpose of this study was to assess the risk of ischaemic heart disease (IHD) and stroke (non-fatal and fatal) among adult ever-users of smokeless tobacco (ST). Design The study design involved a systematic review and meta-analysis of observational studies. Methods Data sources for the review included key electronic databases and reference lists. Studies were included based on design (cohort or case-control), exposure (exclusive use of ST or adjusted for smoking), and outcome (non-fatal and fatal IHD and stroke). Data extraction included reported measures of association (risk ratios (RRs) or odds ratios (ORs)) between ever-use of ST (current or past) and cardiovascular disease (CVD) outcomes among non-smokers, and other study characteristics. The Newcastle-Ottawa scale was used to assess study quality. Summary measures were estimated using random effects models. Results Twenty studies were included in the meta-analyses. Overall, significantly increased risk of IHD deaths (1.15, 95% confidence interval (CI: 1.01-1.30) and stroke deaths (1.39, 95% CI: 1.29-1.49) was found among ever-users of ST. We did not find an overall significant increased risk for IHD (1.14, 95% CI: 0.92-1.42) or stroke (1.01, 95% CI: 0.90-1.13). But geographical variations were marked for IHD, with significant positive association in Asian studies (1.40, 95% CI: 1.01-1.95), and the INTERHEART study, where ST data was mainly reported from Asia (2.23, 95% CI: 1.41-3.53). European studies did not show an increased risk for non-fatal CVD. Conclusion An association was found between ever use of ST and risk of fatal IHD and stroke, consistent with previous reviews. ST consumption also appears to significantly increase risk of non-fatal IHD among users in Asia, but not in Europe.

Omentin-1 and Nonfatal Ischemic Heart Disease in Postmenopausal Women: A Population-Based Study

There is growing evidence that supports the existence of a link between lower levels of circulating omentin-1 and the pathogenesis of coronary atherosclerosis. However, no population-based study has been performed to elucidate the cardioprotective role of this beneficial adipocytokine. A total of 378 healthy, postmenopausal women were randomly selected from 13 clusters in the port city of Bushehr, Iran. The prevalence of nonfatal ischemic heart disease (IHD) was assessed using the Minnesota code with a 12-lead resting electrocardiogram (EKG). EKG with evidence of IHD (IHD-EKG) was defined as myocardial infarction (codes 1.1 and 1.2) and ischemia (codes 1.3, 4.1 to 4.4, 5.1 to 5.3, and 7.1) occurring together. Serum omentin-1 and adiponectin levels were measured using enzyme-linked immunosorbent assay methods. The prevalence of IHD-EKG among the studied population was 41.8% (159 women). Serum levels of omentin-1 were significantly lower in women with ischemic EKG than in normal subjects (geometric mean ×/multiplicative standard deviation, 10.31 ×/2.35 ng/mL versus 12.44 ×/2.12 ng/mL, respectively; P = .038). Multiple logistic regression analysis indicated that higher serum levels of omentin-1 were significantly associated with a lower prevalence of ischemic EKG after adjusting for potential confounders, including classical cardiovascular risk factors and circulating adiponectin levels (odds ratio, 0.48; confidence interval, 0.24 to 0.95; P = .038). A higher level of circulating omentin-1 is independently associated with a lower prevalence of nonfatal IHD in postmenopausal women. The cardioprotective role of this novel adipocytokine needs to be further elucidated in large-scale longitudinal studies. BMI = body mass index EKG = electrocardiogram ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein IHD = ischemic heart disease LDL = low-density lipoprotein.

Multi-wave cohort study of sedentary work and risk of ischemic heart disease.

This study aimed to investigate whether sedentary work is a distinct risk factor for ischemic heart disease (IHD) when the effect of occupational sitting is disentangled from that of occupational physical activity. Data on occupational sitting time and several covariates were derived from the Danish Work Environment Cohort Study (DWECS) conducted every five years from 1990-2005 among the active Danish population. This study was designed as a multi-wave longitudinal study including participants employed at entry. Respondents were followed in national registers, first for death or hospital treatment due to IHD and second for purchase of medication that may prevent IHD from (re)occurring serving as a proxy for IHD. During 145 850 person-years of follow-up, 510 cases of fatal and non-fatal IHD occurred. After adjustment for age, sex, body mass index (BMI), and socioeconomic status, no difference in risk of IHD was observed between sedentary and non-sedentary employees [hazard ratio (HR) 0.95, 95% confidence interval (95% CI) 0.78-1.16]. During 44 949 and 42 456 person-years of follow-up among men and and women, respectively, 1263 men and 1364 women purchased IHD-related medication. No differences in risk were observed between sedentary and non-sedentary participants, either for men or women. A dose-response relationship between occupational sitting time and the risk of IHD was also not detected. This study could not confirm the hypothesis that sedentary work is a distinct risk factor for IHD. Future studies may further investigate the association with objective measures of occupational sitting time.