Monitoring Of Trends And Determinants In Cardiovascular Disease Research Articles

Dietary habits among snus users: a population-based cross-sectional study.

The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use. To examine whether snus users eat unhealthier than never tobacco users. A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models. In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake consisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40]). We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder.

The impact of a patient's social network on emergency surgery for colon cancer.

The aim of this study was to investigate if patients with a weak social network and colon cancer are more likely to be operated as an emergency than those with a strong social network. Data from patients living in Västerbotten County, Sweden, who underwent colon cancer surgery between 2007 and 2020 were extracted from the Swedish Colorectal Cancer Registry (SCRCR). Patients identified were matched against the Västerbotten Intervention Program (VIP) and the longitudinal study Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). These two databases include a survey that includes questions regarding quality and size of the patient's social network. Multivariable logistic regression was used for analysis. Six items from the questions on social network, and the composite variables availability of social integration (AVSI) and availability of attachment (AVAT) were analysed. Data from 801 patients were analysed. The odds ratio for emergency surgery was significantly higher for divorced patients (OR 2.01 (CI 1.03-3.91)) and for male gender (OR 1.51 (CI 1.02-2.24)). A higher OR was seen amongst those with no-one to share feelings with (OR 1.57 (CI 0.82-3.03)) or to comfort them (OR1.33 (CI 0.78-2.28)). Quantitative aspects of social life such as the number of people greater than 10 that feel relaxed at the patient's home, showed a lower OR (OR 0.71(CI 0.35-1.43)). The impact of social network on the risk for emergency surgery for colon cancer is limited. Divorced status and male gender were associated with an increased risk for emergency surgery.

Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts

The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure. In this cross-sectional cohort study, we used clinical data from the Lithium-Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25-74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1-5 years, >5-10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records. From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25-74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25-74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50-0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53-0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43-0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation. Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health. Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section. For the Swedish translation of the Summary see Supplementary Materials section.

The impact of community-based prevention on quality of life-The necessity to control for general health trends the Northern Sweden MONICA study in 2014.

BackgroundThe Västerbotten intervention program (VIP), is a public health promotion program in northern Sweden with the aim of preventing cardiovascular disease. Positive effects have been reported although the evidence is not unequivocal. Since only historical controls have been used, effects from other sources than the program have largely been uncontrolled for and health related quality of life (HRQoL) has not been evaluated.PurposeBy using the neighbouring county of Norrbotten (NB) as the reference population, we compare HRQoL in Västerbotten (VB) and in NB.MethodsIn 2014 the Northern Sweden survey, Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA), examined a random sample from the two counties. HRQoL was measured with the EQ-5D-3L. In total, 1112 subjects aged 40–74 years participated, 516 in VB and 594 in NB. Differences in mean QoL between VB and NB were analysed via Student’s t-test and the Pearson chi-square test.ResultsAverage HRQoL measured by the EQ-5D-index was 0.798 in VB and 0.811 in NB, a difference of 0.013 (p = 0.2, CI -0.009 to 0.036). For subjects aged 45–54 years, the HRQoL was lower in VB than in NB, a difference of 0.048 (p = 0.041; CI 0.002 to 0.0094). Men had higher HRQoL than women, and university educated had higher HRQoL than those without university education. EQ-VAS showed similar results. Subjects from NB and from VB did not differ regarding age, gender and level of education. In NB, HRQoL decrease with age, a pattern not seen in VB.ConclusionsWe found similar levels of HRQoL in VB and in NB.

THE ASSOCIATION BETWEEN N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE AND CARDIOVASCULAR DISEASE IS CONDITIONED BY PRESENCE OF INCREASED ARTERIAL STIFFNESS

Abstract Objective: The aim of this study was to evaluate whether the cardiovascular risk associated with increased N-terminal pro-brain natriuretic peptide (NT-proBNP) is modified by arterial stiffness assessed as carotid to femoral pulse wave velocity (PWV) in apparently healthy individuals. Design and method: This was a population-based cohort study comprising of 1858 healthy subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study. The primary outcome was major adverse cardiovascular events (MACE) after 16 years of follow-up. MACE was defined as cardiovascular death, sudden death, heart failure, arrhythmia, myocardial infarction, chronic ischemic heart disease, cerebrovascular disease, peripheral or central arterial disease. The association between NT-proBNP and MACE was evaluated with Cox proportional-hazards regression stratified for presence of increased arterial stiffness (PWV &gt; 12m/s) and adjusted for traditional risk factors for cardiovascular disease. NT-proBNP was evaluated both as a continuous variable (log transformed) and dichotomously using the 90th percentile as cut-off (110pg/ml) allowing for group-wise comparisons. Results: 314 events were recorded during a median follow-up of 16.0 years (interquartile range: 14.7–16.0). In multivariable regression with both log (NT-proBNP) and log (PWV) included in the model, we found that log (NT-proBNP) was associated with MACE: HR = 1.28 [1.13–1.45] (P &lt; 0.001). There was a significant positive interaction between log (NT-proBNP) and log (PWW): HR = 1.53 [1.02–2.29] (P = 0.042). In subjects with PWV &lt; 12m/s, log (NT-proBNP) was not associated with MACE: HR = 1.07 [0.91–1.26] (P = 0.429). In subjects with increased PWV, log (NT-proBNP) was associated with MACE, HR = 1.68 [1.39–2–04] (P &lt; 0.001). In multivariable categorical analysis using subjects with PWV &lt; 12m/s and NT-proBNP &lt; 110pg/ml as reference group we found: 1) Increased NT-proBNP without increased PWV was not associated with MACE: HR 0.92 [0.52–1.64] (P = 0.790). 2) Increased PWV and normal NT-proBNP showed borderline significant association with MACE HR 1.35 [0.99–1.84] (P = 0.052). 3) Increased PWV and increased NT-proBNP was associated with MACE: HR 3.21 [2.14–4.80] (P &lt; 0.001). Conclusions: The association between increased NT-proBNP and MACE was positively modified by increased arterial stiffness. NT-proBNP was only associated with MACE in subjects with simultaneously increased arterial stiffness.

Comparison of Short- and Long-Term Prognosis between ST-Elevation and Non-ST-Elevation Myocardial Infarction.

Background: Available data comparing long-term prognosis according to the type of acute coronary syndrome (ACS) are scarce, contradictory, and outdated. Our aim was to compare short- and long-term mortality in ST-elevated (STEMI) and non-ST-elevated myocardial infarction (non-STEMI) ACS patients. Methods: Patients presenting with an inaugural ACS during the year 2006 and living in one of the three areas in France covered by the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) registry were included. Results: A total of 1822 patients with a first ACS—1121 (61.5%) STEMI and 701 (38.5%) non-STEMI—were included in the study. At the 28-day follow-up, the mortality rates were 6.7% and 4.7% (p = 0.09) for STEMI and non-STEMI patients, respectively, and after adjustment of potential confounding factors, the 28-day probability of death was significantly lower for non-STEMI ACS patients (Odds Ratio = 0.58 (0.36–0.94), p = 0.03). At the 10-year follow-up, the death rates were 19.6% and 22.8% (p = 0.11) for STEMI and non-STEMI patients, respectively, and after adjustment of potential confounding factors, the 10-year probability of death did not significantly differ between non-STEMI and STEMI events (OR = 1.07 (0.83–1.38), p = 0.59). Over the first year, the mortality rate was 7.2%; it then decreased and stabilized at 1.7% per year between the 2nd and 10th year following ACS. Conclusion: STEMI patients have a worse vital prognosis than non-STEMI patients within 28 days following ACS. However, at the 10-year follow-up, STEMI and non-STEMI patients have a similar vital prognosis. From the 2nd year onwards following the occurrence of a first ACS, the patients become stable coronary artery disease patients with an annual mortality rate in the 2% range, regardless of the type of ACS they initially present with.

Sex- and age-related differences in the predictive capability of circulating biomarkers: from the MONICA 10 cohort

Objectives The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) differed in their ability to predict cardiovascular outcomes beyond traditional risk factors in younger and older men and women without known cardiovascular disease. Design. Prospective population-based cohort study of 1951 individuals from the MONItoring of trends and determinants in Cardiovascular disease (MONICA) study, examined 1993–1994. Participants were stratified into four groups based on sex and age. Subjects aged 41 or 51 years were classified as younger; those aged 61 or 71 years were classified as older. The principal endpoint was death from cardiovascular causes. Predictive capabilities of biomarkers were tested using Cox proportional-hazards regression, Harrell’s concordance-index, net reclassification improvement, and classification and regression tree (CART) analysis. Results. Median follow-up was 18.5 years, during which 19/597 younger men, 100/380 older men, 12/607 younger women, and 46/367 older women had died from a cardiovascular cause. NT-proBNP was independently associated with death from cardiovascular causes among all participants (p ≤ .02) except younger women (p = .70), whereas hs-CRP was associated with this endpoint in men (p ≤ .007), and suPAR in older men only (p < .001). None of the biomarkers improved discrimination ability beyond traditional risk factors (p ≥ .07). However, NT-proBNP enhanced reclassification in men and older women. CART-analysis showed that NT-proBNP was generally of greater value among men, and suPAR among women. Conclusions. Hs-CRP, NT-proBNP, and suPAR displayed different associations with cardiovascular death among apparently healthy younger and older men and women.

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort.

The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1-19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17-1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58-2.29), and suPAR (HR: 1.35, 95% CI: 1.17-1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol (p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.

Dietary Patterns Are Associated with Cardiovascular and Cancer Mortality among Swiss Adults in a Census-Linked Cohort

Defining dietary guidelines requires a quantitative assessment of the influence of diet on the development of diseases. The aim of the study was to investigate how dietary patterns were associated with mortality in a general population sample of Switzerland. We included 15,936 participants from two population-based studies (National Research Program 1A (NRP1A) and Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)—1977 to 1993) who fully answered a simplified 24-h dietary recall. Mortality data were available through anonymous record linkage with the Swiss National Cohort (follow-up of up to 37.9 years). Multiple correspondence analysis and hierarchical clustering were used to define data-driven qualitative dietary patterns. Mortality hazard ratios were calculated for all-cause, cancer and cardiovascular mortality using Cox regression. Two patterns were characterized by a low dietary variety (“Sausage and Vegetables”, “Meat and Salad”), two by a higher variety (“Traditional”, “High-fiber foods”) and one by a high fish intake (“Fish”). Males with unhealthy lifestyle (smokers, low physical activity and high alcohol intake) were overrepresented in the low-variety patterns and underrepresented in the high-variety and “Fish” patterns. In multivariable-adjusted models, the “Fish” (hazard ratio = 0.82, 95% CI (0.68–0.99)) and “High-fiber foods” (0.85 (0.72–1.00)) patterns were associated with lower cancer mortality. In men, the “Fish” (0.73 (0.55–0.97)) and “Traditional” (0.76 (0.59–0.98)) patterns were associated with lower cardiovascular mortality. In summary, our results support the notion that dietary patterns affect mortality and that these patterns strongly cluster with other health determinants.

Score of Adherence to 2016 European Cardiovascular Prevention Guidelines Predicts Cardiovascular and All-Cause Mortality in the General Population

BackgroundGuidelines on cardiovascular (CV) disease prevention promote healthy lifestyle behaviours and CV risk factor control to reduce CV risk. The effect of adherence to these guidelines on CV and all-cause mortality is not well known. MethodsWe assessed the effect of baseline adherence to “2016 European Guidelines on CV Disease Prevention in Clinical Practice” on long-term CV and all-cause mortality in a sample recruited from the French general population. Analysis was on the basis of the Third French Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population-based survey (recruitment period: 1994-1997). We built an adherence score to European guidelines, considering adherence to recommendations for smoking, drinking, physical activity, body mass index, blood pressure, low-density and high-density lipoprotein cholesterol, fasting blood glucose, and diet at baseline. Vital status was obtained 18 years after inclusion. Statistical analysis was on the basis of multivariate Cox modelling. ResultsAdherence score was assessed in 1311 apparently healthy participants aged 35-64 years (73% men). During the follow-up, 186 deaths occurred (41 were due to a CV cause). Considering CV mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score (worse adherence) was 3.12 (95% confidence interval [CI], 1.62-6.01; P = 0.001), compared with subjects in the first, second, or third quartile (best adherence). Considering all-cause mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score was 2.27 (95% CI, 1.68-3.06; P < 0.001). ConclusionsBetter baseline adherence to European guidelines on CV disease prevention was associated with a significantly reduced long-term CV and all-cause mortality in a sample from the French general population.

Trends in out-of-hospital ischemic heart disease mortality for the 25-64 year old population of Kaunas, Lithuania, based on data from the 1988-2012 Ischemic Heart Disease Registry.

The aim of the study was to evaluate trends in out-of-hospital ischemic heart disease (IHD) mortality in the Kaunas, Lithuania population aged 25-64, from 1988 to 2012. The registry was maintained according to the World Health Organisation (WHO) recommendations for the multinational MONICA (MONItoring of trends and determinants in CArdiovascular disease) project. We analysed out-of-hospital deaths from IHD, by sex and age groups, using the linear logistic regression model for identifying trends. In 1988-2012, the out-of-hospital IHD deaths in Kaunas accounted for 78.4% and 68.4%, on average, of all IHD deaths in men and women aged 25-64, respectively. During the study period, the out-of-hospital IHD mortality for the Kaunas population aged 25-64 was 134.5 per 100,000 men and 18.2 per 100,000 women. From 1988 to 2012, the out-of-hospital IHD mortality for men and women aged 25-64 tended to decline by, on average, 8.3% per year (p = 0.269) and 16.2% per year (p = 0.101), respectively; whereas the corresponding rates for men aged 25-44 were declining significantly, by 22.5% per year (p = 0.047). The most significant changes in out-of-hospital IHD mortality were among men aged 25-44 with no previous history of acute myocardial infarction (AMI), in whom the out-of-hospital IHD mortality was significantly declining, by 21.3% per year (p = 0.015); whereas the corresponding rates for men aged 45-54 with a previous history of AMI tended to decline by 20.4% per year (p = 0.114). In 1988-2012, the out-of-hospital IHD deaths of younger men and middle-aged women accounted for the highest percentage of all IHD deaths; and a higher proportion of both men and women with no previous history of AMI, as compared to the proportion of those with a previous history of AMI.

Does Inclusion of Education and Marital Status Improve SCORE Performance in Central and Eastern Europe and Former Soviet Union? Findings from MONICA and HAPIEE Cohorts

Background and ObjectiveThe SCORE scale predicts the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk version of SCORE is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), due to high CVD mortality rates in these countries. Given the pronounced social gradient in cardiovascular mortality in the region, it is important to consider social factors in the CVD risk prediction. We investigated whether adding education and marital status to SCORE benefits its prognostic performance in two sets of population-based CEE/FSU cohorts.MethodsThe WHO MONICA (MONItoring of trends and determinants in CArdiovascular disease) cohorts from the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s (577 atherosclerotic CVD deaths among 14,969 participants with non-missing data). The HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05 (395 atherosclerotic CVD deaths in 19,900 individuals with non-missing data).ResultsIn MONICA and HAPIEE, the high-risk SCORE ≥5% at baseline strongly and significantly predicted fatal CVD both before and after adjustment for education and marital status. After controlling for SCORE, lower education and non-married status were significantly associated with CVD mortality in some samples. SCORE extension by these additional risk factors only slightly improved indices of calibration and discrimination (integrated discrimination improvement <5% in men and ≤1% in women).ConclusionExtending SCORE by education and marital status failed to substantially improve its prognostic performance in population-based CEE/FSU cohorts.

Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang.

BackgroundCardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up.Methods/DesignThis is a prospective, open-label, cluster randomized controlled trial (RCT) with blinded data analysis. The trial will randomize 67 township hospitals with 31,708 participants in three counties in Zhejiang Province. Participants will be identified from existing health records and will comprise adults aged 50 to 74 years, with a calculated 10-year CVD risk of 20% or higher, or diabetes. In the intervention arm, participants will receive a package of interventions including: 1) healthy lifestyle counseling (smoking cessation, and salt, oil, and alcohol reduction); 2) prescription of a combination of drugs (antihypertensives, aspirin, and statin); and 3) adherence support for drug compliance and healthy lifestyle change. In the control arm, participants will receive usual care for hypertension and diabetes management at individual clinicians’ discretion. The primary outcome is the incidence of severe CVD events over 24 months of follow-up. All CVD events will be defined according to the World Health Organization (WHO) monitoring of trends and determinants in cardiovascular disease (MONICA) definitions, diagnosed at the county hospital or higher level, and reported by the Zhejiang surveillance system. Secondary outcomes include: mean systolic and diastolic blood pressure, blood glucose, serum total cholesterol (TC), and adherence to appointments, and drugs and lifestyle changes.DiscussionThis trial focuses on risk reduction of CVD rather than specific diseases. It is not designed to compare therapeutic and healthy lifestyle interventions, but rather their combined effects in primary care settings. Through the trial, we intend to understand the effectiveness of the comprehensive CVD reduction package in routine practice. We also intend to understand the barriers and facilitators to implementing the package, and thus to advise on policy and practice change.Trial registrationCurrent Controlled Trials: ISRCTN58988083

SCORE performance in Central and Eastern Europe and former Soviet Union: MONICA and HAPIEE results

AimsThe Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts.Methods and resultsThe cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7–6.3] and HAPIEE (n = 20 517; HR, 2.6–10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE.ConclusionThe high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.

TGF-β1 content in atherosclerotic plaques, TGF-β1 serum concentrations and incident coronary events

We tested the hypothesis that high TGF-β1 content in atherosclerotic plaques and high TGF-β1 serum levels are associated with lower risk of coronary events in two independent prospective studies. In the prospective Athero-Express biobank study, total TGF-β1 plaque levels were measured in 632 atherosclerotic lesions from patients who underwent carotid endarterectomy. In a population-based case-cohort study within the Monitoring of trends and determinants in cardiovascular disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Augsburg studies, baseline total TGF-β1 serum levels were measured in 333 individuals with and 1728 without incident coronary events. Patients with TGF-β1 content in their plaques above the study median did not have a lower risk of coronary events than patients with lower TGF-β1 levels [adjusted HR (95% CI) 1·46 (0·83-2·53); P = 0·16; mean follow-up 2·6 ± 0·7 years] in the Athero-Express biobank study. Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors, lifestyle factors and survey did not reveal a significant association between TGF-β1 serum levels and incident coronary events [HR (95% CI) for increasing TGF-β1 tertiles 1·0, 1·22 (0·88-1·68), 1·13 (0·82-1·57); P = 0·47; mean follow-up: 10·8 ± 4·6 years] in the MONICA/KORA Augsburg studies. Our results indicate that high TGF-β1 content in human atherosclerotic plaques and high serum levels of TGF-β1 are not associated with reduced risk of coronary events.

Effect of Serum 25-Hydroxyvitamin D on Risk for Type 2 Diabetes May Be Partially Mediated by Subclinical Inflammation

OBJECTIVETo assess the association between serum 25-hydroxyvitamin D (25-OHD) and incident type 2 diabetes and to determine whether the association is mediated by subclinical inflammation.RESEARCH DESIGN AND METHODSUsing a case-cohort design, baseline levels of 25-OHD were measured in 416 case subjects with incident type 2 diabetes and 1,267 noncase subjects selected from a source population of 7,936 middle-aged participants in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) study.RESULTSA significant inverse association was observed between serum 25-OHD and incident type 2 diabetes after adjustment for diabetes risk factors and season. The hazard ratio (HR) and 95% CI comparing tertile extremes was 0.63 (0.44–0.90) (Ptrend = 0.010). Further adjustment for C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, and interferon-γ–inducible protein-10 attenuated this association by 16% (HR 0.73 [0.50–1.05], P = 0.090).CONCLUSIONSVitamin D status is inversely related to type 2 diabetes risk and our data suggest that this association may be partially mediated by subclinical inflammation.

Associations between leptin and the leptin / adiponectin ratio and incident Type 2 diabetes in middle‐aged men and women: results from the MONICA / KORA Augsburg Study 1984–2002

Adipocyte-derived hormones seem to be involved in the development of Type 2 diabetes. Therefore, we assessed the association between the proinflammatory adipokine leptin and incident Type 2 diabetes, taking into account interactions between leptin and the anti-inflammatory adipokine adiponectin. Using a case-cohort design, serum levels of adipokines were measured in 460 cases with incident Type 2 diabetes and 1474 non-cases selected from a source population of 7936 middle-aged subjects participating in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Augsburg cohort study between 1984 and 1995 and followed up until 2002 (mean follow-up 10.9+/-4.7 years). High leptin and low adiponectin levels were associated with an increased Type 2 diabetes risk. The multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing tertile extremes were 1.71 (1.12-2.63) for leptin (top vs. bottom tertile) and 2.65 (1.88-3.76) for adiponectin (bottom vs. top tertile), respectively. There was a significant interaction between leptin and adiponectin, with highest diabetes risk being observed in individuals with high leptin and low adiponectin levels (P = 0.029 for interaction).While the addition of adiponectin to a basic risk factor model improved model prediction (Delta area under the curve 0.011), the change in model prediction was only marginal after the addition of leptin (Delta area under the curve 0.002). Our findings indicate that the two adipokines leptin and adiponectin interact in modulating Type 2 diabetes risk, but adiponectin is more strongly associated with Type 2 diabetes risk than leptin.

Declining renal function after myocardial infarction predicts poorer long-term outcome

In-hospital decline in renal function during the immediate post myocardial infarction (MI) period is known to predict poorer outcome; subsequent chronic change in renal function is less well reported. This study sought to track long-term change in renal function after MI, and assess its correlation with the outcome. Individuals who had sustained a first validated MI in the preceding 2.5-11.5 years were identified from the monitoring of trends and determinants in cardiovascular disease (MONICA) register and were invited to undergo a screening process in 1995, and again in 1998. All deaths were recorded up to the end of 2006. Change in renal function between 1995 and 1998 was available for 500 individuals (mean age 61.6+/-7.3 years, 74.8% men). Change in (Delta) calculated estimated glomerular filtration rate (eGFR) was normally distributed, with a mean crude fall in eGFR of 1.91+/-9.47 ml/min per 1.73 m. This corresponded to a -1.9+/-13.3% change in eGFR, or -0.8+/-3.6 ml/min/1.73 m2 per year. Delta eGFR correlated negatively with baseline eGFR (r=l-0.307, P<0.001). The first tertile (with the largest decline in eGFR) had an adjusted hazard ratios of 1.86 (1.14-3.03) for all cause mortality and 2.06 (1.13-3.74) for cardiovascular death, compared to the third tertile. A rise in creatinine of greater than 0.3 mg/dl carried adjusted hazard ratios of 2.27 (1.13-4.57) and 3.61 (1.73-7.54) for all cause mortality and cardiovascular death, respectively. Chronic change in renal function after MI is predictive of long-term prognosis.

Association between PPARα gene polymorphisms and myocardial infarction

PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the expression of genes that are involved in lipid metabolism, tissue homoeostasis and inflammation. Consistent rodent and human studies suggest a link between PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for coronary artery disease. In the present study, we comprehensively evaluated common genetic variations within the PPARalpha gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPARalpha gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single SNP analysis showed significant association with the disease phenotype [OR (odds ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551]. Moreover, we identified a protective three-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02). Subsequently, we were able to confirm the single SNP and haplotype association results in an independent second case-control cohort with 667 cases from the Regensburg Myocardial Infarction Family Study and 862 control individuals from the WHO (World Health Organization) MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker haplotype respectively). From these cross-sectional association results, we provide evidence that common variations in the PPARalpha gene may influence the risk of myocardial infarction in a European population.

Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis

The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status--or dysfibrinolysis--in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status (high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P < 0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P < 0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women.