Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study.

BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study

ABSTRACT BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

Determinants of social inequalities in stroke incidence across Europe: a collaborative analysis of 126 635 individuals from 48 cohort studies.

BACKGROUND: Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe. MATERIALS AND METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) Study comprises 48 cohorts recruited mostly in the 1980s and 1990s in four European regions using standardised procedures for baseline risk factor assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, generating 3788 first stroke events during a median follow-up of 10 years, we estimated differences in stroke rates and HRs for the least versus the most educated individuals. RESULTS: Compared with their most educated counterparts, the overall age-adjusted excess hazard for stroke was 1.54 (95% CI 1.25 to 1.91) and 1.41 (95% CI 1.16 to 1.71) in least educated men and women, respectively, with little heterogeneity across populations. Educational class inequalities accounted for 86-413 and 78-156 additional stroke events per 100 000 person-years in the least compared with most educated men and women, respectively. The additional events were equivalent to 47%-130% and 40%-89% of the average incidence rates. Inequalities in risk factors accounted for 45%-70% of the social gap in incidence in the Nordic countries, the UK and Lithuania-Kaunas (men), but for no more than 17% in Central and South Europe. The major contributors were cigarette smoking, alcohol intake and body mass index. CONCLUSIONS: Social inequalities in stroke incidence contribute substantially to the disease rates in Europe. Healthier lifestyles in the most disadvantaged individuals should have a prominent impact in reducing both inequalities and the stroke burden.

Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts: Implications for prevention.

Background The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention. Methods We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke. Results Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% (95% confidence interval + 0.1%, +6.2%) in men and of 1.5% (-1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% (95% CI: -5.6%, +0.3%) and obese: -3.6% (-7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% (+0.1%, +7.0%) and of 2.6% (-0.5%, +5.6%), respectively, compared with their more educated counterparts. Conclusions Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.

Timing and Type of Alcohol Consumption and the Metabolic Syndrome - ELSA-Brasil.

The prevalence of the metabolic syndrome is rising worldwide. Its association with alcohol intake, a major lifestyle factor, is unclear, particularly with respect to the influence of drinking with as opposed to outside of meals. We investigated the associations of different aspects of alcohol consumption with the metabolic syndrome and its components. In cross-sectional analyses of 14,375 active or retired civil servants (aged 35-74 years) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we fitted logistic regression models to investigate interactions between the quantity of alcohol, the timing of its consumption with respect to meals, and the predominant beverage type in the association of alcohol consumption with the metabolic syndrome. In analyses adjusted for age, sex, educational level, income, socioeconomic status, ethnicity, smoking, body mass index, and physical activity, light consumption of alcoholic beverages with meals was inversely associated with the metabolic syndrome (≤4 drinks/week: OR = 0.85, 95%CI 0.74-0.97; 4 to 7 drinks/week: OR = 0.75, 95%CI 0.61-0.92), compared to abstention/occasional drinking. On the other hand, greater consumption of alcohol consumed outside of meals was significantly associated with the metabolic syndrome (7 to 14 drinks/week: OR = 1.32, 95%CI 1.11-1.57; ≥14 drinks/week: OR = 1.60, 95%CI 1.29-1.98). Drinking predominantly wine, which occurred mostly with meals, was significantly related to a lower syndrome prevalence; drinking predominantly beer, most notably when outside of meals and in larger quantity, was frequently associated with a greater prevalence. In conclusion, the alcohol-metabolic syndrome association differs markedly depending on the relationship of intake to meals. Beverage preference-wine or beer-appears to underlie at least part of this difference. Notably, most alcohol was consumed in metabolically unfavorable type and timing. If further investigations extend these findings to clinically relevant endpoints, public policies should recommend that alcohol, when taken, should be preferably consumed with meals.

Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study.

BACKGROUND AND AIMS: Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort. METHODS: 8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis. RESULTS: While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis. CONCLUSIONS: These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD.

Educational class inequalities in the incidence of coronary heart disease in Europe.

OBJECTIVE: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations. METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals. RESULTS: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women. CONCLUSIONS: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.

Identification of Heart Failure Events in Medicare Claims: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: We examined the accuracy of Medicare heart failure (HF) diagnostic codes in the identification of acute decompensated (ADHF and chronic stable (CSHF) HF. METHODS AND RESULTS: Hospitalizations were identified from medical discharge records for Atherosclerosis Risk in Communities (ARIC) study participants with linked Medicare Provider Analysis and Review (MedPAR) files for the years 2005-2009. The ARIC study classification of ADHF and CSHF, based on adjudicated review of medical records, was considered to be the criterion standard. A total 8,239 ARIC medical records and MedPAR records meeting fee-for-service (FFS) criteria matched on unique participant ID and date of discharge (68.5% match). Agreement between HF diagnostic codes from the 2 data sources found in the matched records for codes in any position (κ > 0.9) was attenuated for primary diagnostic codes (κ < 0.8). Sensitivity of HF diagnostic codes found in Medicare claims in the identification of ADHF and CSHF was low, especially for the primary diagnostic codes. CONCLUSION: Matching of hospitalizations from Medicare claims with those obtained from abstracted medical records is incomplete, even for hospitalizations meeting FFS criteria. Within matched records, HF diagnostic codes from Medicare show excellent agreement with HF diagnostic codes obtained from medical record abstraction. The Medicare data may, however, overestimate the occurrence of hospitalized ADHF or CSHF.

Artificially Sweetened Beverage Consumption Is Positively Associated with Newly Diagnosed Diabetes in Normal-Weight but Not in Overweight or Obese Brazilian Adults.

BACKGROUND: Recent animal studies suggest that artificially sweetened beverage (ASB) consumption increases diabetes risk. OBJECTIVE: We examined the relation of ASB intake with newly diagnosed diabetes and measures of glucose homeostasis in a large Brazilian cohort of adults. METHODS: We used cross-sectional data from 12,884 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). ASB use was assessed by questionnaire and newly diagnosed diabetes by a 2-h 75-g oral glucose tolerance test and/or glycated hemoglobin. Logistic and linear regression analyses were performed to examine the association of ASB consumption with diabetes and continuous measures of glucose homeostasis, respectively. RESULTS: Although ASB consumption was not associated with diabetes in logistic regression analyses after adjustment for body mass index (BMI; in kg/m(2)) overall, the association varied across BMI categories (P-interaction = 0.04). Among those with a BMI <25, we found a 15% increase in the adjusted odds of diabetes for each increase in the frequency of ASB consumption per day (P = 0.001); compared with nonusers, ASB users presented monotonic increases in the adjusted ORs (95% CIs) of diabetes with increased frequency of consumption: 1.03 (0.60, 1.77), 1.43 (0.93, 2.20), 1.62 (1.08, 2.44), and 2.51 (1.40, 4.50) for infrequent, 1-2, 3-4, and >4 times/d, respectively. In linear regression analyses, among normal-weight individuals, greater ASB consumption was also associated with increased fasting glucose concentrations (P = 0.01) and poorer ß-cell function (P = 0.009). No such associations were seen for those with BMI ≥25. In fact, in overweight or obese participants, greater ASB consumption was significantly associated with improved indexes of insulin resistance and 2-h postload glucose. CONCLUSIONS: Normal-weight, but not excess-weight, individuals with greater ASB consumption presented diabetes more frequently and had higher fasting glucose and poorer ß-cell function.

Quantitative Influence of ABO Blood Groups on Factor VIII and Its Ratio to von Willebrand Factor, Novel Observations from an ARIC Study of 11,673 Subjects.

ABO blood groups are known to influence the plasma level of von Willebrand factor (VWF), but little is known about the relationship between ABO and coagulation factor VIII (FVIII). We analyzed the influence of ABO genotypes on VWF antigen, FVIII activity, and their quantitative relationship in 11,673 participants in the Atherosclerosis Risk in Communities (ARIC) study. VWF, FVIII, and FVIII/VWF levels varied significantly among O, A (A1 and A2), B and AB subjects, and the extent of which varied between Americans of European (EA) and African (AA) descent. We validated a strong influence of ABO blood type on VWF levels (15.2%), but also detected a direct ABO influence on FVIII activity (0.6%) and FVIII/VWF ratio (3.8%) after adjustment for VWF. We determined that FVIII activity changed 0.54% for every 1% change in VWF antigen level. This VWF-FVIII relationship differed between subjects with O and B blood types in EA, AA, and in male, but not female subjects. Variations in FVIII activity were primarily detected at low VWF levels. These new quantitative influences on VWF, FVIII and the FVIII/VWF ratio help understand how ABO genotypes differentially influence VWF, FVIII and their ratio, particularly in racial and gender specific manners.

Reproducibility of Left Ventricular Mass by Echocardiogram in the ELSA-Brasil / Reprodutibilidade de Medidas Ecocardiográficas da Massa Ventricular Esquerda no ELSA-Brasil

Background: Echocardiography, though non-invasive and having relatively low-cost, presents issues of variability which can limit its use in epidemiological studies. Objective: To evaluate left ventricular mass reproducibility when assessed at acquisition (online) compared to when assessed at a reading center after electronic transmission (offline) and also when assessed by different readers at the reading center. Methods: Echocardiographers from the 6 ELSA-Brasil study investigation centers measured the left ventricular mass online during the acquisition from 124 studies before transmitting to the reading center, where studies were read according to the study protocol. Half of these studies were blindly read by a second reader in the reading center. Results: From the 124 echocardiograms, 5 (4%) were considered not measurable. Among the remaining 119, 72 (61%) were women, mean age was 50.2 ± 7.0 years and 2 had structural myocardial abnormalities. Images were considered to be optimal/ good by the reading center for 110 (92.4%) cases. No significant difference existed between online and offline measurements (1,29 g, CI 95% −3.60-6.19), and the intraclass correlation coefficient between them was 0.79 (CI 95% 0.71-0.85). For images read by two readers, the intraclass correlation coefficient was 0.86 (CI 95% 0.78-0.91). Conclusion: There were no significant drifts between online and offline left ventricular mass measurements, and reproducibility was similar to that described in previous studies. Central quantitative assessment of echocardiographic studies in reading centers, as performed in the ELSA-Brasil study, is feasible and useful in clinical and epidemiological studies performed in our setting. .

Fundamento: A ecocardiografia, apesar de não invasiva e de relativo baixo custo, tem na variabilidade de medidas repetidas um dos principais limitantes a sua utilização em estudos epidemiológicos. Objetivo: Avaliar a reprodutibilidade da massa ventricular esquerda obtida em centros de investigação (on-line) com aquela obtida em centro de leitura (off-line) e entre medidas realizadas por diferentes avaliadores no centro de leitura. Métodos: Ecocardiografistas dos seis centros de investigação do ELSA-Brasil mediram on-line a massa ventricular esquerda e outras medidas ecocardiográficas de 124 exames antes de enviá-los ao centro de leitura, onde foram lidos off-line de acordo com o protocolo do estudo. Metade desses exames foi medida de forma cega por um segundo leitor. Resultados: Dos 124 exames, cinco (4%) foram considerados não mensuráveis. Dos 119 restantes, 72 (61%) eram de mulheres, com idade média de 50,2 ± 7,0 anos, sendo apenas dois exames com alteração estrutural cardíaca. Em 110 (92,4%) dos exames, as imagens foram consideradas ótimas/boas pelo centro de leitura. Não foram observadas diferenças significativas entre as médias da massa ventricular esquerda obtidas on-line e off-line (1,29 g, IC 95% −3,60-6,19), sendo o coeficiente de correlação intraclasse de 0,79 (IC 95% 0,72-0,85). Para as medidas realizadas no centro de leitura, % 0,78-0,91). Conclusão: Não houve diferenças sistemáticas relevantes na medida da massa ventricular esquerda on-line versus off-line e a reprodutibilidade das medidas foi similar à de estudos anteriores. A realização das medidas em centros de leitura, como utilizado no ELSA-Brasil, é factível e útil em estudos clínico-epidemiológicos realizados em nosso meio. .

Reproducibility of left ventricular mass by echocardiogram in the ELSA-Brasil.

BACKGROUND: Echocardiography, though non-invasive and having relatively low-cost, presents issues of variability which can limit its use in epidemiological studies. OBJECTIVE: To evaluate left ventricular mass reproducibility when assessed at acquisition (online) compared to when assessed at a reading center after electronic transmission (offline) and also when assessed by different readers at the reading center. METHODS: Echocardiographers from the 6 ELSA-Brasil study investigation centers measured the left ventricular mass online during the acquisition from 124 studies before transmitting to the reading center, where studies were read according to the study protocol. Half of these studies were blindly read by a second reader in the reading center. RESULTS: From the 124 echocardiograms, 5 (4%) were considered not measurable. Among the remaining 119, 72 (61%) were women, mean age was 50.2 ± 7.0 years and 2 had structural myocardial abnormalities. Images were considered to be optimal/ good by the reading center for 110 (92.4%) cases. No significant difference existed between online and offline measurements (1,29 g, CI 95% -3.60-6.19), and the intraclass correlation coefficient between them was 0.79 (CI 95% 0.71-0.85). For images read by two readers, the intraclass correlation coefficient was 0.86 (CI 95% 0.78-0.91). CONCLUSION: There were no significant drifts between online and offline left ventricular mass measurements, and reproducibility was similar to that described in previous studies. Central quantitative assessment of echocardiographic studies in reading centers, as performed in the ELSA-Brasil study, is feasible and useful in clinical and epidemiological studies performed in our setting.

Validity of a long-term cardiovascular disease risk prediction equation for low-incidence populations: the CAMUNI-MATISS Cohorts Collaboration study.

BACKGROUND: Before introducing long-term cardiovascular disease (CVD) risk models in clinical practice, their external validity should be investigated. We assessed the validity of the CArdiovascular Monitoring Unit in Northern Italy (CAMUNI) 20-year risk score, developed in Northern Italy, and published previously, when applied to a population with different risk factors distribution and event incidence. METHODS: The validation sample consisted of 5307 35-69 year-old subjects (2418 men) enrolled in Central Italy during the 1980s (Malattia ATerosclerotica Istituto Superiore di Sanità (MATISS) study). Baseline risk factor assessment and follow-up procedures, including MONICA definition of acute events, followed a shared protocol with the derivation cohorts. We estimated model calibration and discrimination (area under the ROC curve, AUC) in the validation set; as well as the net benefit of using the CAMUNI risk score as second-level screening in subjects at different levels of short-term risk. RESULTS: The 20-year risk of event was 14% in men and 7% in women. Model calibration was satisfactory, and the strength of the association between predictors and the endpoint was the same as in the derivation population. The AUC was 0.734 (men) and 0.802 (women). The net benefit of the CAMUNI score was 3.9 (95% confidence interval: 2.1-5.7) and 2.9 (1.7-4.3) in men and women at low 10-year risk, respectively. Among subjects at high short-term risk, a significant net benefit of 9.8 was observed in men only. A pooled CAMUNI-MATISS risk score is provided. CONCLUSIONS: In this low-incidence European population, long-term CVD prediction through the CAMUNI risk score is accurate and it has the potential to improve current primary prevention strategies based on short-term risk scores alone.

Do apolipoproteins improve coronary risk prediction in subjects with metabolic syndrome? Insights from the North Italian Brianza cohort study.

OBJECTIVE: We assessed predictive abilities and clinical utility of CVD risk algorithms including ApoB and ApoAI among non-diabetic subjects with metabolic syndrome (MetS). METHODS: Three independent population-based cohorts (3677 35-74 years old) were enrolled in Northern Italy, adopting standardized MONICA procedures. Through Cox models, we assessed the associations between lipid measures and first coronary events, as well as the changes in discrimination and reclassification (NRI) when standard lipids or apolipoproteins were added to the CVD risk algorithm including non-lipids risk factors. Finally, the best models including lipids or apolipoproteins were compared. RESULTS: During the 14.5 years median follow-up time, 164 coronary events were validated. All measures showed statistically significant associations with the endpoint, while in the MetS subgroup HDL-C and ApoAI (men, HR = 1.59; 95%CI: 0.96-2.65) were not associated. Models including HDL-C plus TC and ApoB plus ApoAI for lipids and apolipoproteins, respectively, showed the best predictive values. When ApoB plus ApoAI replaced TC plus HDL-C, NRI values improved in subjects with MetS (13.8; CI95%: -5.1,53.1), significantly in those previously classified at intermediate risk (44.5; CI95% 13.8,129.6). In this subgroup, 5.5% of subjects was moved in the high (40.0% of expected events) and 17.0% in the low risk class (none had an event at 10 years). CONCLUSIONS: ApoB and ApoAI could improve coronary risk prediction when used as second level biomarkers in non-diabetic subjects with MetS classified at intermediate risk. The absence of cases moved downward suggests the gain in avoiding treatments in non-cases and favor the use of apolipoproteins for risk assessment.

The contribution of educational class in improving accuracy of cardiovascular risk prediction across European regions: The MORGAM Project Cohort Component.

OBJECTIVE: To assess whether educational class, an index of socioeconomic position, improves the accuracy of the SCORE cardiovascular disease (CVD) risk prediction equation. METHODS: In a pooled analysis of 68 455 40-64-year-old men and women, free from coronary heart disease at baseline, from 47 prospective population-based cohorts from Nordic countries (Finland, Denmark, Sweden), the UK (Northern Ireland, Scotland), Central Europe (France, Germany, Italy) and Eastern Europe (Lithuania, Poland) and Russia, we assessed improvements in discrimination and in risk classification (net reclassification improvement (NRI)) when education was added to models including the SCORE risk equation. RESULTS: The lowest educational class was associated with higher CVD mortality in men (pooled age-adjusted HR=1.64, 95% CI 1.42 to 1.90) and women (HR=1.31, 1.02 to 1.68). In men, the HRs ranged from 1.3 (Central Europe) to 2.1 (Eastern Europe and Russia). After adjustment for the SCORE risk, the association remained statistically significant overall, in the UK and Eastern Europe and Russia. Education significantly improved discrimination in all European regions and classification in Nordic countries (clinical NRI=5.3%) and in Eastern Europe and Russia (NRI=24.7%). In women, after SCORE risk adjustment, the association was not statistically significant, but the reduced number of deaths plays a major role, and the addition of education led to improvements in discrimination and classification in the Nordic countries only. CONCLUSIONS: We recommend the inclusion of education in SCORE CVD risk equation in men, particularly in Nordic and East European countries, to improve social equity in primary prevention. Weaker evidence for women warrants the need for further investigations.

Possible race and gender divergence in association of genetic variations with plasma von Willebrand factor: a study of ARIC and 1000 genome cohorts.

The synthesis, secretion and clearance of von Willebrand factor (VWF) are regulated by genetic variations in coding and promoter regions of the VWF gene. We have previously identified 19 single nucleotide polymorphisms (SNPs), primarily in introns that are associated with VWF antigen levels in subjects of European descent. In this study, we conducted race by gender analyses to compare the association of VWF SNPs with VWF antigen among 10,434 healthy Americans of European (EA) or African (AA) descent from the Atherosclerosis Risk in Communities (ARIC) study. Among 75 SNPs analyzed, 13 and 10 SNPs were associated with VWF antigen levels in EA male and EA female subjects, respectively. However, only one SNP (RS1063857) was significantly associated with VWF antigen in AA females and none was in AA males. Haplotype analysis of the ARIC samples and studying racial diversities in the VWF gene from the 1000 genomes database suggest a greater degree of variations in the VWF gene in AA subjects as compared to EA subjects. Together, these data suggest potential race and gender divergence in regulating VWF expression by genetic variations.

Incidence and survival of hospitalized acute decompensated heart failure in four US communities (from the Atherosclerosis Risk in Communities Study).

Most population-based estimates of incident hospitalized heart failure (HF) have not differentiated acute decompensated heart failure (ADHF) from chronic stable HF nor included racially diverse populations. The Atherosclerosis Risk in Communities Study conducted surveillance of hospitalized HF events (age ≥55 years) in 4 US communities. We estimated hospitalized ADHF incidence and survival by race and gender. Potential 2005 to 2009 HF hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes; 6,168 records were reviewed to validate ADHF cases. Population estimates were derived from US Census data; 50% of eligible hospitalizations were classified as ADHF, of which 63.6% were incident ADHF and 36.4% were recurrent ADHF. The average incidence of hospitalized ADHF was 11.6 per 1,000 persons, aged ≥55 years, per year, and recurrent hospitalized ADHF was 6.6 per 1,000 persons/yr. Age-adjusted annual ADHF incidence was highest for black men (15.7 per 1,000), followed by black women (13.3 per 1,000), white men (12.3 per 1,000), and white women (9.9 per 1,000). Of incident ADHF events with heart function assessment (89%), 53% had reduced the ejection fraction (heart failure with reduced ejection fraction [HFrEF]) and 47% had preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]). Black men had the highest proportion of acute HFrEF events (70%); white women had the highest proportion of acute HFpEF (59%). Age-adjusted 28-day and 1-year case fatality after an incident ADHF was 10.4% and 29.5%, respectively. Survival did not differ by race or gender. In conclusion, ADHF hospitalization and HF type varied by both race and gender, but case fatality rates did not. Further studies are needed to explain why black men are at higher risk of hospitalized ADHF and HFrEF.

Long-term prediction of major coronary or ischaemic stroke event in a low-incidence Southern European population: model development and evaluation of clinical utility.

OBJECTIVE: To develop a long-term prediction model of first major cardiovascular event and to assess its clinical utility in a low-incidence European population. SETTING: Four independent population-based cohorts enrolled between 1986 and 1993 in Northern Italy. PARTICIPANTS AND METHODS: N=5247 35-year-old to 69-year-old men and women free of cardiovascular disease at baseline. Absolute 20-year risk of first fatal or non-fatal coronary or ischaemic stroke event (monitoring trends and determinants in cardiovascular disease (MONICA) validated) was estimated from gender-specific Cox models. MAIN OUTCOME MEASURES: Model discrimination (area under the receiver operating characteristic (ROC)-curve, AUC). 'High-risk' subjects were identified based on several threshold values for the 20-year predicted risk. Clinical utility was defined in terms of fraction of missed events (events among those considered at low-risk) and unnecessary treatment (false:true positive ratio). A net benefit curve was also provided. RESULTS: Kaplan-Meier 20-year risk was 16.1% in men (315 events) and 6.1% in women (123 events). Model discrimination (AUC=0.737 in men, 0.801 in women) did not change significantly as compared to 10-year prediction time interval. In men, with respect to risk stratification based on the number of risk factors, a 20% predicted risk cut-off would miss less events (36% vs 50%) and reduce unnecessary treatment (false:true positive ratio 2.2 vs 3.0); the net benefit was higher over the whole range of threshold values. Similar considerations hold for women. CONCLUSIONS: Long-term prediction has good discrimination ability and is clinically useful for risk stratification in primary prevention. A clinical utility analysis is recommended to identify the optimal stratification according to different public health goals.

Troponin T and N-terminal pro-B-type natriuretic peptide: a biomarker approach to predict heart failure risk--the atherosclerosis risk in communities study.

BACKGROUND: Among the various cardiovascular diseases, heart failure (HF) is projected to have the largest increases in incidence over the coming decades; therefore, improving HF prediction is of significant value. We evaluated whether cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal pro-B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with incident HF, improve HF risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Using sex-specific models, we added cTnT and NT-proBNP to age and race ("laboratory report" model) and to the ARIC HF model (includes age, race, systolic blood pressure, antihypertensive medication use, current/former smoking, diabetes, body mass index, prevalent coronary heart disease, and heart rate) in 9868 participants without prevalent HF; area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification improvement (NRI), and model fit were described. RESULTS: Over a mean follow-up of 10.4 years, 970 participants developed incident HF. Adding cTnT and NT-proBNP to the ARIC HF model significantly improved all statistical parameters (AUCs increased by 0.040 and 0.057; the continuous NRIs were 50.7% and 54.7% in women and men, respectively). Interestingly, the simpler laboratory report model was statistically no different than the ARIC HF model. CONCLUSIONS: cTnT and NT-proBNP have significant value in HF risk prediction. A simple sex-specific model that includes age, race, cTnT, and NT-proBNP (which can be incorporated in a laboratory report) provides a good model, whereas adding cTnT and NT-proBNP to clinical characteristics results in an excellent HF prediction model.

A diet pattern with more dairy and nuts, but less meat is related to lower risk of developing hypertension in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) study.

Dietary intake among other lifestyle factors influence blood pressure. We examined the associations of an "a priori" diet score with incident high normal blood pressure (HNBP; systolic blood pressure (SBP) 120-139 mmHg, or diastolic blood pressure (DBP) 80-89 mmHg and no antihypertensive medications) and hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or taking antihypertensive medication). We used proportional hazards regression to evaluate this score in quintiles (Q) and each food group making up the score relative to incident HNBP or hypertension over nine years in the Atherosclerosis Risk of Communities (ARIC) study of 9913 African-American and Caucasian adults aged 45-64 years and free of HNBP or hypertension at baseline. Incidence of HNBP varied from 42.5% in white women to 44.1% in black women; and incident hypertension from 26.1% in white women to 40.8% in black women. Adjusting for demographics and CVD risk factors, the "a priori" food score was inversely associated with incident hypertension; but not HNBP. Compared to Q1, the relative hazards of hypertension for the food score Q2-Q5 were 0.97 (0.87-1.09), 0.91 (0.81-1.02), 0.91 (0.80-1.03), and 0.86 (0.75-0.98); p(trend) = 0.01. This inverse relation was largely attributable to greater intake of dairy products and nuts, and less meat. These findings support the 2010 Dietary Guidelines to consume more dairy products and nuts, but suggest a reduction in meat intake.