Gerhard Sulo

Favourable trends in incidence of AMI in Norway during 2001–2009 do not include younger adults: a CVDNOR project

Aims Acute myocardial infarction (AMI) incidence reflects levels of risk factors in the general population and influences coronary heart disease mortality rates. We examined trends in AMI incidence in Norway during 2001–2009 and potential differences between sex and age groups. Methods All AMI hospitalizations (ICD9 410; ICD10 I21, I22) and coronary out-of-hospital deaths (ICD9 410–414; ICD10 I20–I25) in Norway for individuals ≥25 years were obtained during 1994–2009. Incident AMI was defined as a hospitalization or out-of-hospital death due to AMI with no prior hospitalization for AMI during the previous 7 years. Age-standardized and age-group specific rates were calculated and expressed per 100,000 persons. The annual changes in rates were obtained from Poisson regression analyses. The total change in incidence rates during 2001–2009 were then calculated based on the estimated annual change. Results We identified 148,522 incident AMIs (41% women; 21% out-of-hospital deaths) during 2001–2009. Incidence rates declined by 24% (incidence rate ratio, IRR, 0.76, 95% CI 0.75–0.78). Out-of-hospital death rates declined more than hospitalization rates (IRR 0.54, 95% CI 0.52–0.56 vs. IRR 0.84, 95% CI 0.82–0.85; p < 0.001). The decline in incidence rates was observed among those 45 years or older. Among persons under 45 years, AMI incidence rates did not change significantly, while hospitalization rates increased with 11%. Conclusion AMI incidence rates declined during 2001–2009. The decline was due to reductions in rates of out-of-hospital deaths and hospitalizations in individuals 45 years or older. A worrying increase in hospitalization rates was observed in those younger than 45 years.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries

Objective To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. Methods Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed. Results In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m2 for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol. Conclusions CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

Neopterin and kynurenine-tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study.

BACKGROUND Immune system activation is involved in atherosclerosis. Neopterin production and tryptophan catabolism through the kynurenine pathway, measured by the kynurenine-tryptophan ratio (KTR), are induced by interferon gamma, thus both are considered markers of cell mediated immune activation. This study prospectively investigated their predictive value on acute coronary events among Norwegian community-dwelling older adults without previous coronary heart disease. METHODS 1112 men and 1631 women, 71-74 years old were examined during 1997-99 as part of the Hordaland Health Study. They were followed until an acute coronary event (defined as unstable angina, non-fatal or fatal acute myocardial infarction or sudden death) or December 31, 2006. Kaplan-Meier hazard curves were constructed for quartiles of plasma neopterin and KTR. Cox proportional hazards models adjusted for sex, body mass index, smoking, hypertension, renal function and cholesterol were used to examine the relation between neopterin and KTR quartiles and the study endpoint. RESULTS Median (interquartile range) values were 8.6 (7.2-10.4) nmol/L for neopterin and 25.8 (25.3-31.1) nmol/μmol for KTR. During the follow up, 265 participants had at least one acute coronary event. Increased baseline levels of plasma neopterin and KTR were associated with continuous increased risk of developing the study endpoint (P-values for trend <0.001 and 0.019, respectively). Adjusted hazard ratios comparing the fourth quartile to the first were 1.65 (95% CI; 1.11-2.47; P=0.013) for neopterin and 1.57 (95% CI 1.03-2.39; P=0.036) for KTR. CONCLUSION Plasma neopterin and KTR levels predict acute coronary events in older adults without previous coronary heart disease.

Kynurenines as predictors of acute coronary events in the Hordaland Health Study

BACKGROUND The kynurenine pathway, the main metabolic route of tryptophan degradation, has been related to inflammatory responses. Some of its metabolites, referred to as kynurenines, have been associated with prevalence of coronary heart disease (CHD) in cross-sectional studies. This prospective study aims to investigate whether increased concentrations of kynurenines are associated with risk of acute coronary events, defined as unstable angina pectoris, acute myocardial infarction, and/or sudden death in community-dwelling elderly. METHODS The baseline examinations included 2819 individuals aged 71-74 years recruited into the Hordaland Health Study. Participants with known CHD at baseline were excluded from analyses. Baseline plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid were measured by LC-MS/MS. During a median follow-up period of 10.8 years, with linkage to acute coronary event endpoints through the CVDNOR project, hazard ratios (HRs) for acute coronary events (n = 376) were estimated using Cox proportional hazard analyses. RESULTS After adjustment for established cardiovascular risk factors, HRs (95% CI) comparing the 4th vs 1st quartile were 1.86 (1.19-2.92) for kynurenine and 1.72 (1.19-2.49) for 3-hydroxykynurenine. Tryptophan, kynurenic acid, anthranilic acid, xanthurenic acid and 3-hydroxyanthranilic acid were not associated with acute coronary events. CONCLUSIONS Kynurenine and 3-hydroxykynurenine were associated with increased risk of acute coronary events in community-dwelling elderly without a known history of CHD. These results suggest the involvement of the kynurenine pathway in the early development of CHD, and their potential usefulness to estimate CHD risk.

Trends in Acute Myocardial Infarction Event Rates and Risk of Recurrences After an Incident Event in Norway 1994 to 2009 (from a Cardiovascular Disease in Norway Project)

We explored trends in acute myocardial infarction (AMI) event rates in Norway during 1994 to 2009 and trends in the 6-month, 1-year, and 3-year risk of recurrences after an incident AMI during 2001 to 2008 in men and women ≥25 years. Trends in AMI event rates (incident and recurrent) were analyzed using joinpoint regression analyses and expressed as annual percentage change (APC) in rates. Trends in AMI recurrences were explored using conditional risk models for ordered events in Cox regression. Analyses were stratified by gender and age group. Overall, AMI rates were stable during 1994 to 2002 but declined during 2002 to 2009 (APC = -2.0; 95% confidence interval [CI] -3.1 to -0.9 in men; APC = -2.1; 95% CI -3.8 to -0.5 in women). In the younger age group, rates declined during the whole study period in men (APC = -0.6; 95% CI -1.0 to -0.3) but not in women. Among older patients, no changes were observed during 1994 to 2002, whereas rates declined during 2002 to 2009 (APC = -2.6; 95% CI -3.8 to -1.4 in men; APC = -2.4; 95% CI -4.0 to -0.7 in women). During 2001 to 2008, in the older age group, the 6-month, 1-year, and 3-year risks of recurrences were reduced annually by 4.7%, 4.3%, and 5.4% in men and 5.2%, 5.0%, and 5.7% in women (all ptrend <0.001), respectively. No changes were observed in the younger age group. In conclusion, favorable trends in AMI event rates and recurrences observed in Norway were mostly seen among patients aged 65+ years, whereas less favorable trends were observed among younger patients, especially among women.

Trends in 28-day and 1-year mortality rates in patients hospitalized for a first acute myocardial infarction in Norway during 2001–2009: a “Cardiovascular disease in Norway” (CVDNOR) project

The aim of this study was to investigate the trends in 28‐day and 1‐year mortality rates in patients hospitalized for a first acute myocardial infarction (AMI) in Norway during the period 2001–2009. Potential age group and gender differences in these trends were also examined.

Educational Inequalities in Acute Myocardial Infarction Incidence in Norway: A Nationwide Cohort Study

Background Increasing differences in cardiovascular disease (CVD) mortality across levels of education have been reported in Norway. The aim of the study was to investigate educational inequalities in acute myocardial infarction (AMI) incidence and whether such inequalities have changed during the past decade using a nationwide longitudinal study design. Methods Data on 141 332 incident (first) AMIs in Norway during 2001–2009 were obtained through the Cardiovascular Disease in Norway (CVDNOR) project. Educational inequalities in AMI incidence were assessed in terms of age-standardised incidence rates stratified on educational level, incidence rate ratios (IRR), relative index of inequality (RII) and slope index of inequality (SII). All calculations were conducted in four gender and age strata: Men and women aged 35–69 and 70–94 years. Results AMI Incidence rates decreased during 2001–2009 for all educational levels except in women aged 35–69 among whom only those with basic education had a significant decrease. In all gender and age groups; those with the highest educational level had the lowest rates. The strongest relative difference was found among women aged 35–69, with IRR (95% CI) for basic versus tertiary education 3.04 (2.85–3.24)) and RII (95% CI) equal to 4.36 (4.03–4.71). The relative differences did not change during 2001–2009 in any of the four gender and age groups, but absolute inequalities measured as SII decreased among the oldest men and women. Conclusions There are substantial educational inequalities in AMI incidence in Norway, especially for women aged 35–69. Relative inequalities did not change from 2001 to 2009.

Incident coronary heart disease after Preeclampsia: Role of reduced fetal growth, preterm delivery, and parity

Background Preeclampsia is a severe pregnancy disorder often complicated by reduced fetal growth or preterm delivery and is associated with long‐term maternal morbidity and mortality. We aimed to assess the association between preeclampsia phenotypes and risk of subsequent coronary heart disease and maternal cardiovascular mortality. Methods and Results Women aged 16 to 49 years who gave birth during 1980–2002 and registered in the Medical Birth Registry of Norway were followed prospectively (1–29 years) for an incident major coronary event and mortality through linkage with the Cardiovascular Disease in Norway 1994–2009 (CVDNOR) project and the Norwegian Cause of Death Registry. Preeclampsia was subdivided based on the presence of a child born small for gestational age or preterm delivery. Among 506 350 women with 1 to 5 singleton births, there were 1275 (0.3%) occurrences of major coronary event, 468 (0.1%) cardiovascular deaths, and 5411 (1.1%) deaths overall. Compared with women without preeclampsia, the hazard ratio (95% CI) for major coronary event was 2.1 (1.73–2.65) after preeclampsia alone, 3.3 (2.37–4.57) after preeclampsia in combination with small for gestational age, and 5.4 (3.74–7.74) after preeclampsia in combination with preterm delivery. Analyses distinguishing women with 1 (n=61 352) or >1 (n=281 069) lifetime pregnancy and analyses with cardiovascular mortality as outcome followed the same pattern. Conclusions The occurrence of major coronary events was increased among women with preeclampsia and highest for preeclampsia combined with a child born small for gestational age and/or preterm delivery.

Non-fasting triglycerides predict incident acute myocardial infarction among those with favourable HDL-cholesterol: Cohort Norway*:

Aims to prospectively evaluate the risk of acute myocardial infarction (AMI) associated with non-fasting triglyceride levels. Methods a health survey of 140,790 Norwegians free of known coronary heart disease at baseline (1994–2003) were followed through December 2009 via record linkages to the Cause of Death Registry and hospital discharge diagnoses in the CVDNOR project, and evaluated in Cox proportional hazards analyses. Results a total of 3219 (4.8%) men and 1434 (1.9%) women developed an AMI. Women had a steeper gradient risk with increasing triglyceride decile than men, where the highest (≥2.88 mmol/l) compared to the lowest decile (<0.7 mmol/l) was associated with an age-adjusted 4.7-fold excess risk in women in contrast to a 2.8-fold excess risk in men (interaction term, p < 0.001). A significant at-risk HDL-C (<1.0 mmol/l for men and <1.3 mmol/l for women) by triglyceride interaction term was observed. HRs increased with increasing triglyceride quartile in participants with a favourable HDL-C after multivariable adjustment (p for trend <0.001), but triglycerides did not significantly predict AMI among those with low HDL-C. For those with favourable HDL-C, net reclassification index identified a 10% and 14% improvement in classification for men and women, respectively. Conclusion non-fasting triglyceride levels among individuals with favourable HDL-C may help identify a subset of individuals at risk for CHD. Further research is warranted in evaluating non-fasting triglycerides in CHD prediction.

Educational inequalities in 28 day and 1-year mortality after hospitalisation for incident acute myocardial infarction — A nationwide cohort study

BACKGROUND There is little recent evidence on the impact of comorbidities and access to revascularisation procedures on educational inequalities in mortality after acute myocardial infarction (AMI). The aim of the study was to investigate educational inequalities in mortality among all patients hospitalised for an incident AMI during 2001-2009 in Norway. METHODS Data were obtained through the Cardiovascular Disease in Norway (CVDNOR) project. Incident AMI was defined as an AMI-hospitalisation without any AMI-events in the previous 7 years. Education was categorised as basic, upper secondary or tertiary (college/university). Cox regression was used to assess educational differences in 28-day and 29-365-day mortality after an incident AMI in terms of hazard ratios and relative index of inequality (RII). RII can be interpreted as the ratio in mortality between the 0 th and the 100th percentile of the education distribution. RESULTS 111 993 incident AMIs were included (39.4% women). Among patients aged 35-69, RIIs (95% CI) adjusted for age, sex and year were 1.86 (1.59-2.18) and 2.10 (1.69-2.59) for 28-day and 29-365-day mortality respectively. Among patients aged 70-94 the corresponding RIIs were 1.12 (1.06-1.30) and 1.28 (1.19-1.38). Educational inequalities in mortality were attenuated after adjustment for comorbidities and revascularisation, but were still significant. Educational inequalities did not decrease during 2001-2009. CONCLUSION Educational inequalities in both 28-day and 29-365 day mortality were strong and persistent during 2001-2009. Further research is needed to investigate if these disparities are driven by inequalities in the severity of the AMI or by inequitable access to treatment and rehabilitation.