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Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Background: CD3(+) CD56(+) natural killer T (NKT)-like cells are a subset of T cells characterized by expression of NK receptors and potent antitumour activity. It has also been suggested that they have a role in autoimmune disease, and levels of NKT-like cells are elevated in patients with coronary disease., Objectives: To investigate whether high levels of CD3(+) CD56(+) NKT-like cells are associated with an increased incidence of cardiovascular disease and a lower incidence of cancer., Methods: This was a prospective study including 700 subjects participating in the baseline investigation of the Malmö Diet and Cancer study between 1991 and 1994. Leucocytes obtained at the baseline investigation and stored at -140 °C were thawed and CD3(+) CD56(+) cells analysed by flow cytometry. The incidence rates of cancer and coronary events during a mean follow-up of 15 years were determined through national registers., Results: Subjects in the lowest tertile of interferon (IFN)-γ-expressing CD4(+) CD56(+) cells were found to have an increased risk of incidence of coronary events (log-rank test: P < 0.05). This association remained significant after controlling for age, sex, smoking, body mass index, hypertension, diabetes and the Th1/Th2 and Th1/Treg cell ratios in a Cox proportional hazards regression model (hazard ratio 1.98, 95% confidence interval 1.24-3.16), but not when the LDL/HDL ratio was included in the model. There were no associations between CD3(+) CD56(+) NKT-like cells and incident cancer., Conclusions: The present results could not confirm the hypothesis that low levels of CD3(+) CD56(+) NKT-like cells are associated with a higher incidence of cancer and a lower incidence of cardiovascular disease. However, we found that low levels of IFN-γ-expressing CD3(+) CD4(+) CD56(+) NKT-like cells were associated with an increased incidence of coronary events and that this association may be dependent on lipoproteins., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Background: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent., Objectives: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry., Methods: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors., Results: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47)., Conclusions: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle cell-dependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosclerotic plaques have received less attention. The present study aimed to investigate whether plasma levels of the smooth muscle cell growth factor epidermal growth factor (EGF), heparin-binding-EGF (HB-EGF), and platelet-derived growth factor correlate with plaque phenotype and incidence of CEs., Approach and Results: HB-EGF, EGF and platelet-derived growth factor were measured in plasma from 202 patients undergoing carotid endarterectomy and in 384 incident CE cases and 409 matched controls recruited from the Malmö Diet and Cancer cohort. Significant positive associations were found between the plasma levels of all 3 growth factors and the collagen and elastin contents of the removed plaques. CE cases in the Malmö Diet and Cancer cohort had lower levels of HB-EGF in plasma, whereas no significant differences were found for EGF and platelet-derived growth factor. After adjusting for cardiovascular risk factors in a Cox proportional hazard model, the hazard ratio for the highest HB-EGF tertile was 0.61 (95% confidence interval, 0.47-0.82; P<0.001)., Conclusions: The associations between high levels of smooth muscle cell growth factors in plasma and a more fibrous plaque phenotype as well as the association between low levels of HB-EGF and incident CEs point to a potential clinically important role for factors that contribute to plaque stabilization by stimulating smooth muscle cells., (© 2014 American Heart Association, Inc.)

Aims: Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied., Methods and Results: Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall >or=30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3-1.9, P < 0.0001 and 1.6, 95% CI 1.2-2.1, P = 0.001] and diastolic BP fall >or=15 mmHg (HR: 1.4, 95% CI 1.1-1.9, P = 0.024 and 1.7, 95% CI 1.1-2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction., Conclusion: Orthostatic hypotension can be detected in approximately 6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease.

Background: Data regarding the association between lipoprotein-associated phospholipase A2 (Lp-PLA(2)) level and incidence of cardiovascular (CV) events are conflicting. This prospective urban population-based study explored the relationship between baseline Lp-PLA(2) activity and mass, respectively, levels and incidence of first coronary heart disease (CHD) and ischemic stroke, respectively., Methods: Lp-PLA(2) activity and mass were assessed in 5393 (60% women) subjects who participated in the Malmö Diet and Cancer Study cardiovascular program during 1991-1994., Results: In all 347 subjects had an event (195 CHD and 152 ischemic strokes) during the follow-up period (mean 10.6+/-1.7 years). In an age-, sex- and CV risk factors-adjusted Cox regression analysis, comparing top to bottom tertile of Lp-PLA(2) activity, the relative risk [RR; 95% confidence interval (CI)] for incident CHD and ischemic stroke events were 1.48; 0.92-2.37 and RR: 1.94; 1.15-3.26, respectively. The corresponding figures for Lp-PLA(2) mass were 0.95; 0.65-1.40 and RR: 1.92; 1.20-3.10., Conclusion: Elevated levels of Lp-PLA(2) activity and mass, respectively, were in this study, independently of established risk factors related to the incidence of ischemic stroke but after adjustment for lipids not significant related to incident CHD.

Hypertension has been associated with increased case-fatality rates among individuals who subsequently suffer from acute coronary events. It is unknown whether inflammation modifies this relationship. This population-based study explored the effects of inflammation and hypertension on incidence of coronary event, and on the fatality of the future events. Blood pressure (BP) and five inflammation-sensitive plasma proteins (ISPs, fibrinogen, orosomucoid, alpha 1-antitrypsin, haptoglobin and ceruloplasmin) were determined in 6071 healthy men. During the mean follow-up of 19 years, 679 men had a first coronary event (non-fatal myocardial infarction or death from coronary heart disease). Of them, 197 (29%) were fatal cases (death during the first day). As expected, hypertension was associated with increased incidence of coronary events and increased proportion of fatal cases. At all levels of BP, high ISPs (> or =2 ISPs in top quartile) significantly added to the incidence of events. Men with high ISPs had the highest case-fatality rates. The difference in case-fatality rate between men with and without high ISPs was, however, significant only in men with normal BP (<130/85 mm Hg) (33 vs 19%, P < 0.05), and not in men with moderate or severe hypertension (> or =160/100 mm Hg) (40 vs 35%, P = 0.32). High ISPs add to the incidence of coronary events at all levels of BP. Hypertension and inflammation are both independently associated with increased case-fatality in subjects who later have an acute coronary event. The influence of ISPs on the case-fatality rate seems to be most important in men with normal BP.

Context: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke., Objective: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data., Data Sources: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators., Study Selection: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded., Data Extraction: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias., Data Synthesis: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design., Conclusions: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Objectives: To evaluate the incidence of coronary events (CE) and case fatality in relation to common carotid intima-media thickness (IMT) and carotid plaque over a median follow up of 7 years., Subjects: A total of 5163 Swedish middle-aged men and women with no prior myocardial infarction and/or stroke., Methods and Results: The associations amongst B-mode ultrasound determined common carotid IMT, carotid plaque (focal IMT > 1.2 mm) and carotid stenosis (lumen reduction of >15%) and incident CE, were investigated in relation to cardiovascular risk factor levels. Age- and sex-adjusted common carotid IMT, carotid plaque and carotid stenosis were significantly (P < 0.05) related to future CE. Adjustment for established risk factors generally reduced the hazard rate ratios. However, the continuous measure of common carotid IMT, carotid plaque and carotid stenosis were significantly related to incident CE, even after risk factor adjustment. The strength of the associations between common carotid IMT and CE was only to a small extent reduced after adjustment for presence of carotid plaque. There were no statistically significant associations between common carotid IMT, carotid plaque or carotid stenosis and short-term case-fatality rates (28-days mortality) or long-term case-fatality rates (5-years mortality)., Conclusions: The results show an association between common carotid IMT and incident CE, independently of cardiovascular risk factors and carotid plaque. However, there was no association with short-term or long-term mortality after a CE.

Background: Approximately 40% of men suffering a first acute coronary event die the first day; most of them never reach hospital. It is largely unknown whether a low-grade inflammation in healthy men predicts the fatality of future coronary events., Methods and Results: Five inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 apparently healthy men, 680 of whom had a first coronary event [nonfatal myocardial infarction (MI) or death from coronary heart disease (CHD)] over a mean follow-up of 19 years. Of the 680 men who had a coronary event, 197 died the first day and 228 died within 28 days. Elevated ISPs were significantly associated with both nonfatal MI and CHD death, but the relative risks for CHD death were higher than for nonfatal MI. Among men who subsequently had a coronary event, the proportion of fatal events was related to the number of elevated ISPs at the baseline examination. The proportions who died the first day were 26%, 25%, 29%, and 35%, respectively, among men with 0, 1, 2, and > or =3 elevated ISPs (trend: P=0.01, adjusted for risk factors). The corresponding proportions who died within 28 days were 30%, 31%, 34%, and 38%, respectively (trend: P=0.03)., Conclusions: Men who have been exposed to a low-grade inflammation many years earlier have higher fatality in future coronary events, with a higher proportion of CHD deaths and less nonfatal MI. This relation should be regarded when inflammatory markers are considered for risk assessment in primary prevention.

Objective: To study incidence, prognosis and risk factors of ventricular arrhythmias in men with and without asymptomatic non-invasively detected cardiovascular disease (CVD)., Design: Prospective cohort study with 11 years' follow-up. The subjects went through 24-h ambulatory electrocardiographic (ECG) registrations and non-invasive examinations of leg and carotid arteries at the baseline examination., Setting: Malmö, Sweden., Subjects: Four hundred and forty-three randomly selected 68-year-old men., Main Outcome Measures: Mortality and cardiac event rates during an 11-year period., Results: Frequent or complex arrhythmias (Lown class 2-5) were common in men both with and without CVD. However, the associated prognoses were different. In men with CVD, frequent or complex arrhythmias were associated with increased cardiac event rates (P = 0.001) and increased mortality (P = 0.054). This pattern was also found in men with asymptomatic leg and carotid artery disease, although the frequency of arrhythmia in Lown class 2-5 was similar to that in men without CVD. Men with angina pectoris or previous myocardial infarction in combination with leg or carotid artery disease had the most arrhythmias and the worst prognosis. No relationship between frequent or complex arrhythmias and mortality or cardiac events was found in men without CVD. In a logistic regression, smoking and diabetes mellitus were significant and independent determinants of frequent or complex arrhythmias in men with CVD. High alcohol consumption was associated with arrhythmias in men without CVD., Conclusion: Ambulatory ECG recording is a feasible method to improve risk assessment in men with CVD. In this group, frequent or complex arrhythmias are associated with smoking and diabetes mellitus.

The objective of this long-term ECG (LTER) study in 394 68-year-old men, selected at random from the general population of Malmö, Sweden, was to determine the prevalence and occurrence of cardiac arrhythmias and their impact on morbidity and mortality from IHD. According to Lown classification, 29.4% (116 men) had ventricular arrhythmia (VA) group 4-5. Serious ventricular arrhythmia (Lown group 4-5) was more common in men with asymptomatic ischaemic type ST-segment depression (STD) than in those without it (37.8% vs. 26.7%: P less than 0.05). During the mean follow-up period of 53.1 months there were seven IHD deaths (6%) among the 116 patients with VA, Lown 4-5, and nine IHD deaths (3.2%) among the 278 patients without serious VA, Lown 0-3, (P = 0.26). Six and three of these deaths, respectively, were considered to be sudden (P = 0.022). The increased cardiac event rate (fatal or non-fatal MI or deaths due to chronic IHD) associated with a serious ventricular arrhythmia disappeared when history of IHD at baseline and occurrence of STD during LTER were taken into account. The study did not provide any evidence to suggest that ventricular arrhythmia was triggered by myocardial ischaemia. Five of 9 (56%) deaths due to IHD in men with STD occurred among the 38% (37/98) of patients who belonged to Lown class 4-5. It is concluded that the prognostic information derived from LTER can be improved by combined monitoring of STD and ventricular arrhythmias.

'Men born in 1914', from Malmö, Sweden, is a cohort study of the morbidity and mortality of cardiovascular diseases among 68-year-old men in an urban population. Ambulatory long-term ECG recording was part of the health examination that these men were invited to undergo in 1982. Five hundred attended (80.5%) of the 621 invited. Ninety-eight of the 394 men in whom the ECG recording was technically satisfactory had at least one episode with horizontal or downsloping ST segment depression greater than or equal to 0.1 mV. The median total duration of ST segment depression was 135 min. 90% of these episodes were not preceeded by any increase in heart rate. In only eight of the 47 men who reported an occurrence of chest symptoms during the recording period did ST segment depression and chest symptoms occur simultaneously. 43 months after the health examination, 33 (8.4%) men had died. The mortality in men without ST segment depression and without any history of coronary heart disease was 6.5%. The incidence of fatal and non-fatal myocardial infarction in men without ST depression greater than or equal to 0.1 mV and without a history of IHD was 2.3%. Men with ST depression greater than or equal to 0.1 mV in comparison with this group had a 4.4 times greater relative risk. The risk in men with both ST segment depression greater than or equal to 0.1 mV and history of coronary heart disease was 16.0 times greater. This study shows that asymptomatic ST segment depression is a frequent finding in elderly men. The occurrence of asymptomatic ST segment depression is associated with an increased cardiovascular mortality. This increased mortality is independent of a history compatible with angina pectoris or previous myocardial infarction.

Background: It has been proposed that vascular progenitor cells play an important role in vascular repair, but their possible clinical importance in cardiovascular disease has not been fully characterized. Vascular endothelial growth factor A, placental growth factor and stem cell factor (SCF) are three growth factors that are important in recruiting vascular progenitor cells. In this study, we investigated the association between the plasma levels of these growth factors and incident coronary events (CEs). Methods: Levels of the three growth factors were measured using the proximity extension assay technique in baseline plasma samples from 384 subjects with a first CE (mean follow-up 14.0 ± 4.3 years) and 409 event-free control subjects matched by sex and age, as well as in homogenates from 201 endarterectomy specimens. Results: After controlling for known cardiovascular disease risk factors in a Cox regression model, subjects in the lowest SCF tertile had a hazard ratio of 1.70 (95% confidence interval 1.14-2.54) compared with subjects in the highest SCF tertile. Lower SCF levels were also associated with more severe carotid disease, less fibrous atherosclerotic plaques and an increased incidence of heart failure. Expression of the SCF receptor c-kit was demonstrated in the subendothelial layer and fibrous cap of human atherosclerotic plaques. Smokers and subjects with diabetes had decreased levels of SCF compared with control subjects. Conclusion: To our knowledge, this is the first clinical study to provide evidence to support a key role for SCF and progenitor cells in vascular repair. We suggest that the SCF-c-kit pathway may be a promising biomarker and therapeutic target in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background and purpose The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease ( CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke ( IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. Methods We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores ( GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease ( LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment ( TOAST)] separately. Results SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio ( OR) = 1.12; 95% confidence interval ( CI): 1.04-1.20; P = 0.002] as well as LVD ( OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. Conclusions Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants. [ABSTRACT FROM AUTHOR]

. Schiopu A, Hedblad B, Engström G, Struck J, Morgenthaler NG, Melander O (Lund University, Skåne University Hospital Malmö, Malmö, Sweden; BRAHMS GmbH/Thermo Fisher Scientific, Hennigsdorf, Germany). Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population-based study. J Intern Med 2012; 272: 484-491. Objectives: A number of inflammatory biomarkers such as C-reactive protein (CRP) are independent predictors of cardiovascular risk. The inflammatory biomarker procalcitonin (PCT) has previously been shown to be associated with coronary atherosclerosis and the metabolic syndrome. We evaluated the ability of PCT to predict future cardiovascular events in a population of apparently healthy individuals. Design: We measured plasma PCT levels in 3713 subjects with no previous history of cardiovascular disease, randomly selected from the Malmö Diet and Cancer cohort. The correlation between PCT concentration and the incidence of coronary events, stroke and cardiovascular death over a median follow-up period of 13.7 years was studied using a Cox regression analysis corrected for age, sex, CRP level, traditional risk factors and renal function. Results: Age and sex were strong determinants of PCT; the concentration of PCT was significantly higher in men than in women. PCT was associated with several of the established cardiovascular risk factors (CRP, hypertension, diabetes and renal function) as determined by multivariate linear regression. Of note, PCT was inversely correlated with HDL and smoking. We found significant correlations between PCT levels, coronary events and cardiovascular death. However, these relationships lost statistical significance when the analysis was corrected for CRP and the traditional risk factors. Conclusions: This is the largest population-based prospective study to demonstrate a positive association between plasma PCT levels and cardiovascular risk in subjects with no previous history of acute cardiovascular events. However, the high degree of covariation between PCT and other cardiovascular risk factors limits the value of PCT as an independent cardiovascular risk predictor. [ABSTRACT FROM AUTHOR]

Objective. Moderately reduced lung function in apparently healthy subjects has been associated with incidence of coronary events. However, whether lung function is related to the fatality of the future events is unknown. This study explored whether reduced forced vital capacity ( FVC) and forced expiratory volume in 1 s ( FEV1) in initially healthy men is related to the fatality of the future coronary events. Design. Prospective cohort study. Setting. Population-based study from Malmö, Sweden. Subjects. A total of 5452 healthy men, 28–61 years of age. Main outcome measures. Incidence of first coronary events was monitored over a mean follow-up of 19 years. The fatality of the future events was studied in relation to FEV and FVC. Results. A total of 589 men suffered a coronary event during follow-up, 165 of them were fatal during the first day. After risk factors adjustment, low FEV or FVC were associated with incidence of coronary events (fatal or nonfatal) and this relationship was most pronounced for the fatal events. Amongst men who subsequently had a coronary event, the case-fatality rates were higher in men with low FEV or FVC. Adjusted for risk factors, the odds ratio for death during the first day was 1.00 (reference), 1.63 (95% CI: 0.9–3.1), 1.86 (1.0–3.5) and 2.06 (1.1–3.9), respectively, for men with FVC in the 4th, 3rd, 2nd, and lowest quartiles (trend: P < 0.05). FEV showed similar relationships with the fatality rates. Conclusion. Apparently healthy men with moderately reduced lung function have higher fatality in future coronary events, with a higher proportion of coronary heart disease deaths and less nonfatal myocardial infarction. [ABSTRACT FROM AUTHOR]

Objective. To study to what extent geographical differences of the mortality from ischaemic heart disease (IHD) can be accounted for by the 28-day case fatality rate (CFR) following first hospital admittance for acute myocardial infarction (MI) and whether the geographical pattern of survival has any relationship with socio-economic circumstances. Design. Register-based surveillance study. Setting. Seventeen residential areas in Malmö, Sweden. Subjects. All 5533 patients were admitted during 1986–1995 for a first acute MI at Malmö University Hospital. Main outcome measures. CFR is based on record linkage with national registers. Area-specific cardiovascular and socio-economic scores (SES) are based on previous cross-sectional studies. Results. In patients below 75 years of age, differences of the 28-day CFR accounted for 20–30% of the geographical variance in mortality from IHD. No corresponding association was found in older age groups. Patients from areas with low SES had the highest CFR, 23.8%. The odds ratios of fatal outcome for patients from areas with median and low SES (versus high SES) were 1.23 (95% CI: 1.01–1.50) and 1.25 (95% CI: 1.03–1.52), respectively ( P for trend: 0.060). The strongest correlation was observed in men below 75 years of age ( P for trend: 0.007). During the study period there was an improvement of the survival rate for patients from high and medium SES areas but no corresponding change for patients coming from areas having a low SES. Conclusions. In patients below 75 years, geographical differences of the mortality from IHD were related to differences of the 28-day CFR following hospital admittance for a first MI. Rates of survival were inversely related to socio-economic circumstances in the patient's residential area. [ABSTRACT FROM AUTHOR]

Objectives: Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow-up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long-term total mortality.Setting: Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden.Subjects: A total of 6074 nondiabetic, middle-aged, healthy Swedish males. SCREENING EXAMINATION: We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow-up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration.Main Outcome Measures: Total mortality and cardiac event (CE) rate for IHD.Results: Unadjusted relative risks (RRs) for both death and CE were J-shaped with the highest relative risk (RR: 1.4-1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow-up. The risk of death in hyperinsulinaemic men, defined on the basis of 2-h insulin level, increased with time of follow-up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05-1.65], even after adjustment for other risk factors.Conclusions: Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow-up time. The 2-h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long-term follow-up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long-term risk of mortality and IHD. [ABSTRACT FROM AUTHOR]

Assesses to what extent the incidence of coronary events and death related to smoking, hypertension, hyperlipidemia and diabetes is modified by obesity. Increase in the risk associated with obesity by exposure to other atherosclerotic risk factors of which smoking seems to be the most important; Need to evaluate the preventive potential of the associations in controlled trials.