Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment.

BACKGROUND: Observational findings for high-density lipoprotein (HDL)-mediated cholesterol efflux capacity (HDL-CEC) and coronary heart disease (CHD) appear inconsistent, and knowledge of the genetic architecture of HDL-CEC is limited. OBJECTIVES: A large-scale observational study on the associations of HDL-CEC and other HDL-related measures with CHD and the largest genome-wide association study (GWAS) of HDL-CEC. PARTICIPANTS/METHODS: Six independent cohorts were included with follow-up data for 14,438 participants to investigate the associations of HDL-related measures with incident CHD (1,570 events). The GWAS of HDL-CEC was carried out in 20,372 participants. RESULTS: HDL-CEC did not associate with CHD when adjusted for traditional risk factors and HDL cholesterol (HDL-C). In contradiction, almost all HDL-related concentration measures associated consistently with CHD after corresponding adjustments. There were no genetic loci associated with HDL-CEC independent of HDL-C and triglycerides. CONCLUSION: HDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations.

Natriuretic Peptides and Risk of Type 2 Diabetes: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

OBJECTIVE: Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD. RESEARCH DESIGN AND METHODS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models. RESULTS: Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19]; P multiplicative interaction = 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs. 0.81 [0.66; 0.99]; P multiplicative interaction = 0.236). CONCLUSIONS: NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project.

BACKGROUND: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. METHODS: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. RESULTS: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. CONCLUSION: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort.

AIMS: Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. METHODS AND RESULTS: N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. CONCLUSION: In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.

Decomposing the educational gradient in allostatic load across European populations. What matters the most: differentials in exposure or in susceptibility?

BACKGROUND: We investigate whether socially disadvantaged individuals are more susceptible to the detrimental effects of smoking and alcohol intake on allostatic load (AL), a marker of physiological 'wear and tear', resulting from adaptation to chronic stress. METHODS: In a cross-sectional analysis, 27 019 men and 26 738 women aged 35-74 years were identified from 21 European cohorts in the BiomarCaRE consortium. We defined three educational classes (EDs) according to years of schooling and an AL score as the sum of z-scores of eight selected biomarkers from the cardiovascular, metabolic and inflammatory systems. We used the Oaxaca-Blinder decomposition to disentangle the ED gradient in AL score into the differential exposure (DE, attributable to different distribution of smoking and alcohol intake across EDs) and the differential susceptibility (DS, attributable to a different effect of risk factors on AL across EDs) components. RESULTS: Less-educated men (mean AL difference: 0.68, 95% CI 0.57 to 0.79) and women (1.52, 95% CI 1.40 to 1.64) had higher AL scores. DE accounted for 7% and 6% of the gradient in men and women, respectively. In men, combining smoking and alcohol intake, DS accounted for 42% of the gradient (smoking DS coefficient=0.177, 26% of the gradient; alcohol DS coefficient=0.109; 16%, not statistically significant). DS contribution increased to 69% in metabolic markers. DS estimates were consistent across age groups, irrespective of comorbidities and robust to unmeasured confounding. No DS was observed in women. CONCLUSIONS: In men, a DS mechanism substantially contributes to the educational class gradient in allostatic load.

Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

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.

Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts: Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe).

BACKGROUND: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood. METHODS: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years. RESULTS: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90 versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index. CONCLUSIONS: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis.

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.

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.

Clinical and laboratory characteristics of active and healthy aging (AHA) in octogenarian men.

OBJECTIVES: To investigate clinical and laboratory variables associated with good subjective and objective health ("active and healthy aging", AHA) in a cohort of octogenarian men. DESIGN: Cross-sectional analyses of a longitudinal study. SETTING: The Helsinki Businessmen Study in Finland. PARTICIPANTS: A socioeconomically homogenous cohort of men (baseline n = 3293), born in 1919-1934, has been followed up from the 1960s. From 2000, the men have been regularly sent mailed questionnaires and mortality has been retrieved from national registers. MEASUREMENTS: In 2010 survey, AHA was defined as independently responding to the mailed survey, feeling happy without cognitive or functional impairments and without major diseases. In 2010/11, a random subgroup men was clinically investigated and survivors with healthy and nonhealthy aging were compared. RESULTS: By 2010, 1788 men of the baseline cohort had died, and 894 men responded to the mailed survey. 154 (17.2 %) of those fulfilled the present AHA criteria. Increasing number of criteria were negatively (P < 0.001) related to short-term mortality. In 2011, a random sample of 458 men were clinically investigated, 90 of them with AHA. Men with AHA had higher serum LDL cholesterol and diastolic blood pressure (partially explained by less frequent drug use) but no significant difference was observed in other risk factors. Men with AHA had significantly faster walking speed (P < 0.001), stronger handgrip (P = 0.017), better self-rated health and less phenotypic frailty (P = 0.02). CONCLUSION: Less than 5 % enjoyed active and healthy aging over their life course, which was significantly related to markers of frailty but not to the traditional vascular risk factors.

Aging of the population may not lead to an increase in the numbers of acute coronary events: a community surveillance study and modelled forecast of the future.

OBJECTIVE: To examine the incidence, mortality and case fatality of acute coronary syndrome (ACS) in Finland during 1993-2007 and to create forecasts of the absolute numbers of ACS cases in the future, taking into account the aging of the population. DESIGN: Community surveillance study and modelled forecasts of the future. SETTING AND METHODS: Two sets of population-based coronary event register data from Finland (FINAMI and the National Cardiovascular Disease Register (CVDR)). Bayesian age-period-cohort (APC) modelling. PARTICIPANTS: 24 905 observed ACS events in the FINAMI register and 364 137 in CVDR. MAIN OUTCOME MEASURES: Observed trends of ACS events during 1993-2007, forecasted numbers of ACS cases, and the prevalence of ACS survivors until the year 2050. RESULTS: In the FINAMI register, the average annual declines in age-standardised incidence of ACS were 1.6% (p<0.001) in men and 1.8% (p<0.001) in women. For 28-day case fatality of incident ACS, the average annual declines were 4.1% (p<0.001) in men and 6.7% (p<0.001) in women. Findings in the country-wide CVDR data were consistent with the FINAMI register. The APC model, based on the CVDR data, suggested that both the absolute numbers of ACS events and the prevalence of ACS survivors reached their peak in Finland around 1990, have declined since then, and very likely will continue to decline until 2050. CONCLUSIONS: The ACS event rates and absolute numbers of cases have declined steeply in Finland. The declining trends are likely to continue in the future despite the aging of the population.

Socioeconomic inequalities in the morbidity and mortality of acute coronary events in Finland: 1988 to 2002.

PURPOSE: To examine the changes in socioeconomic disparities in the incidence of coronary heart disease (CHD) and mortality in Finland and to analyze the effects of the severe economic recession of the early 1990s on these disparities. METHODS: The population-based FINAMI Myocardial Infarction (MI) register recorded all suspected MI events among men and women ages 35 to 99 years in four geographical areas of Finland. Record linkage with the files of Statistics Finland provided us with detailed information on the indicators of socioeconomic status (SES; income, education, and profession). Rates were expressed per 100,000 inhabitants of each socioeconomic group per year and age-standardized to the European standard population. Poisson regression was used for analyzing rate ratios and time trends of coronary events in different socioeconomic groups. RESULTS: The mortality rate ratio of coronary events among 35- to 64 year-old men was 5.21 (95% confidence interval, 4.23-6.41) when the lowest income sixth to the highest income sixth were compared. Among women, the respective rate ratio was 11.13 (5.77-21.45). Significant differences in the incidence and 28-day mortality by SES were seen also in the older age groups. Some socioeconomic differences were found in the proportions of patients receiving thrombolysis or undergoing early revascularization. No substantial changes were observed in inequalities between the socioeconomic groups during the study period. CONCLUSIONS: The excess CHD morbidity and mortality among persons with lower SES is still considerable in Finland, but the economic recession did not widen the differences.

Socioeconomic indicators and the risk of acute coronary heart disease events: comparison of population-based data from the United States and Finland.

PURPOSE: We wished to determine whether a gradient of association of low socioeconomic status with incidence of coronary heart disease was present in two population-based cohorts, one from United States and the other from Finland. METHODS: Using data from the Atherosclerosis Risk in Communities (ARIC) cohort and the Finnish FINRISK cohort, we estimated, with Cox proportional hazard regression models, incidence of sudden cardiac death (SCD), non-sudden cardiac death (NSCD), and non-fatal myocardial infarction (NFMI) for strata of income and education (follow-up: 1987-2001). In both cohorts, incidence rates of the three outcomes increased across all socioeconomic status exposure categories. RESULTS: Low education was associated with increased hazard of NFMI in both cohorts and with increased risk of SCD among ARIC women. Low income was significantly associated with increased hazard of all three outcomes among ARIC women and with increased hazard of cardiac death among ARIC men. In FINRISK, low income was significantly associated with increased risk of SCD only. Risk of SCD in the low income categories was similar for both cohorts. Smoking, alcohol consumption, and race (ARIC only) did not appreciably alter effect estimates in either cohort. CONCLUSIONS: Indices of low SES show similar associations with increased risk of cardiac events in Finland and in United States.

Resistin is an indicator of the metabolic syndrome according to five different definitions in the Finnish Health 2000 survey.

BACKGROUND: Resistin is a peptide hormone secreted mainly from human monocytes and macrophages. It has an unclear association with the metabolic syndrome, which is a cluster of cardiovascular risk factors such as glucose intolerance, central obesity, insulin resistance, dyslipidemia, and hypertension. We examined the association of resistin with metabolic syndrome and its components in a population-based cohort. METHODS: A subsample of a large Finnish cross-sectional health examination survey (the Health 2000 Survey) was studied. Resistin was measured using an in-house assay based on the DELFIA® technique in 1,508 Finnish men and women aged 45-74 years. Metabolic syndrome was defined according to five different definitions. RESULTS: Resistin levels were higher in the subjects with metabolic syndrome when compared to the subjects without metabolic syndrome (P < 0.05 for every metabolic syndrome criterion). In logistic regression analysis, a high resistin level was an independent predictor of the prevalence of metabolic syndrome (P < 0.05 for every criterion). Resistin was positively associated with waist circumference, tumor necrosis factor-α, and insulin resistance assessed by the homeostasis model and inversely with total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after adjusting for age, gender, and body mass index (P < 0.05 for all). CONCLUSIONS: These results clarify the controversial association of resistin in obesity and metabolic syndrome, suggesting that a high resistin level is associated with clustering of metabolic disturbances.

Prevalence and prognostic value of poor R-wave progression in standard resting electrocardiogram in a general adult population. The Health 2000 Survey.

AIMS: We examined the prevalence and prognostic impact of poor R-wave progression (PRWP) in a standard electrocardiogram (ECG) in a general population. METHODS: Data and standard resting ECG recording were collected from a large nationally representative (random sample) health examination survey conducted in Finland in 2000-2001. The final study population consisted of 5613 individuals. RESULTS: The prevalence of PRWP (defined as RV3 < or = 3 mm and RV2 < or = RV3) was 7.0% in women and 2.7% in men (P< or = 0.001 for difference). During follow-up of 70 +/- 9 months (mean +/- SD), 317 patients died (5.6%). Both all-cause and cardiovascular mortality was higher in the group with PRWP than in those without PRWP in both women and men. In Cox regression analysis after adjustment for age, hypertension, diabetes, previous myocardial infarction, and coronary heart disease, the relative risk for all-cause mortality for PRWP was 1.69 (95% CI 0.89-3.22, P=0.112) for men and 2.00 (95% CI 1.28-3.13, P=0.002) for women. For cardiovascular mortality the relative risk for individuals with PRWP was 1.85 (0.74-4.65, P=0.19) for men and 3.02 (1.54-5.93, P=0.001) for women. CONCLUSIONS: PRWP is a common ECG finding and predicts risk for total and cardiovascular mortality in women in a general population.

Stroke morbidity in Swedish- and Finnish-speaking populations of Turku, Finland.

OBJECTIVES: To examine differences in the morbidity and mortality of stroke between the Finnish- and Swedish-speaking populations in Turku, taking into account the socioeconomic differences between these groups. DESIGN: The population-based FINMONICA and FINSTROKE stroke registers recorded 5,135 stroke events among persons aged 25-99 years in Turku during 1988-1998. Events in persons aged > or =75 years were not registered in 1993-1995. Information on these persons' native language and socioeconomic status (SES) (measured by taxable income, profession and years of education) were obtained by record linkage with the files of Statistics Finland. RESULTS: Swedish-speaking men had a lower attack rate of ischaemic stroke than Finnish-speaking men (270, 95% Confidence Interval (CI) 214-326 versus 370, 95% CI 352-389, per 100,000 inhabitants per year) and the difference remained significant after adjustment for SES. Among women, the attack rates of ischaemic stroke were similar in both language groups. CONCLUSIONS: The attack rate of ischaemic stroke was lower among Swedish-speaking than among Finnish-speaking men. This difference was not totally explained by the higher SES of the Swedish-speaking population.

The effect of smoking in midlife on health-related quality of life in old age: a 26-year prospective study.

BACKGROUND: Smoking shortens life expectancy by 7 to 10 years. However, it is unclear whether the enhanced longevity of nonsmokers produces increased disability and decreased quality of life during these extra final years. This study evaluates the long-term effect of smoking in midlife on health-related quality of life (HRQoL) in old age. METHODS: Prospective cohort study with a 26-year follow-up of 1658 white men (born 1919-1934) of similar socioeconomic status who were participating in the Helsinki Businessmen Study. All men were healthy at baseline in 1974, when cardiovascular risk factors and smoking habits were assessed. The participants were reevaluated with the use of mailed questionnaires in 2000; HRQoL was measured with the use of the RAND 36-Item Health Survey (similar to the Medical Outcomes Study Short-Form Health Survey) and related to the baseline smoking status. Total mortality through 2000 was determined from Finnish national registers. RESULTS: Participants who had never smoked (n = 614) lived a mean of 10 years longer than heavy smokers (>20 cigarettes daily; n = 188). Among survivors in 2000 (n = 1131), the never-smokers had the highest (ie, best) scores on all RAND 36-Item Health Survey scales. The differences were greatest between never-smokers and heavy smokers, ranging from 4 points on the scale of social functioning to 14 points on the physical functioning scale. The physical component summary score showed a graded deterioration of HRQoL with an increasing number of cigarettes smoked daily (P = .01). CONCLUSIONS: During the 26-year follow-up of this socioeconomically homogeneous male cohort, HRQoL deteriorated with an increase in daily cigarettes smoked in a dose-dependent manner. Never-smokers lived longer than heavy smokers, and their extra years were of better quality.

Non-participation and mortality in different socioeconomic groups: the FINRISK population surveys in 1972-92.

BACKGROUND: Declining response rates pose a serious threat to the validity of estimates derived from epidemiological studies. If respondents and non-respondents differ systematically from each other, there can be a bias in the results of the study. A population-based cohort study was conducted to investigate disparities in socioeconomic structure between respondents and non-respondents and the contribution of these disparities to socioeconomic differences in total and cardiovascular mortality. DESIGN: Data comprised 32,354 male and female participants and 4890 non-participants aged 35-74 years who belonged to the sample in one of the five FINRISK surveys in 1972, 1977, 1982, 1987 or 1992 in Finland. They were followed up for 9 years and 6 months. RESULTS: It was found that the lower socioeconomic groups were over-represented among non-respondents both in men and women. When comparing the relative risk of death using the highest socioeconomic group of the participants as the reference group, it was found that although the socioeconomic gradient was similar for participants and non-participants-that is, lower groups had a higher risk of death-the risk was at a higher level among non-respondents. CONCLUSIONS: Basing analysis on participants does not distort the relative risk of death associated with socioeconomic position. However, it does underestimate the absolute risk.

Population-based register of acute myocardial infarction: manual of operations.

Cardiovascular disease is the leading cause of death and hospitalization in both sexes in nearly all countries of Europe. The main forms of cardiovascular disease are ischaemic heart disease and stroke. The magnitude of the problem contrasts with the shortage, weak quality and comparability of data available in most European countries. Innovations in medical, invasive and biological treatments have substantially contributed to the escalating costs of health services. It is therefore urgent to obtain reliable information on the magnitude and distribution of the disease for both adequate health planning (including preventive strategies) and clinical decision making with correct cost-benefit assessments.A stepwise surveillance procedure based on standardized data collection, appropriate record linkage and validation methods was set up by the EUROCISS Project (EUROpean Cardiovascular Indicators Surveillance Set) to build up comparable and reliable indicators (attack rate and case fatality) for the surveillance of acute myocardial infarction/acute coronary syndrome at population level. This manual of operations is intended for health professionals and policy makers and provides a standardized and simple model for the implementation of a population-based register. It recommends to start from a minimum data set and then follow a stepwise procedure. Before implementing a population-based register, it is important to identify the target population under surveillance which should preferably cover a well-defined geographical and administrative area or region representative of the whole country for which population data and vital statistics (mortality and hospital discharge records at minimum) are routinely collected and easily available each year. All cases among residents should be recorded even if the case occurs outside the area. Validation of a sample of fatal and nonfatal events is mandatory.