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Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmö Diet and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation analysis was used to examine associations between smoking and blood cadmium levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques. The total association with smoking status (never smokers, 2 categories of former smokers, and current smokers) was split into direct and indirect association, and the proportion mediated was estimated. The adjusted estimated plaque prevalence was approximately 27% among never smokers. We identified both a direct and an indirect pathway between smoking and carotid plaques; the indirect association, through cadmium, was observed among current smokers and former smokers who had quit smoking less than 15 years before. For current smokers, the prevalence ratio for plaque was 1.5, with 60%-65% of the association with smoking being mediated through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45% was mediated through cadmium. Long-time former smokers had a prevalence ratio of 1.2, but none of the association was mediated through cadmium. In conclusion, about two-thirds of the proatherosclerotic association with smoking was mediated by cadmium.

Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development., Methods and Results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women., Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Purpose: This study explored whether complement factor 3 (C3) in plasma is associated with incidence of diabetes in a population-based cohort. We also identified genetic variants related to C3 and explored whether C3 and diabetes share common genetic determinants., Methods: C3 was analyzed in plasma from 4368 nondiabetic subjects, 46 to 68 years old, from the Malmö Diet and Cancer Study. Incidence of diabetes was studied in relationship to C3 levels during 17.7± 4.4 years of follow-up. Genotypes associated with C3 were identified in a genome-wide association study. Diabetes Genetics Replication and Meta-Analysis and the European Genetic Database were used for in silico look-up., Results: In all, 538 (12.3%) subjects developed diabetes during 18 years of follow-up. High C3 was significantly associated with incidence of diabetes after risk factor adjustments (hazard ratio comparing 4th vs 1st quartile, 1.54 (95% confidence interval, 1.13 to 2.09; P = 0.005). C3 was associated with polymorphisms at the complement factor H locus (P < 10-8). However, no relationship with diabetes was observed for this locus. Another eight loci were associated with C3 with P < 10-5. One of them, the glucose kinase regulatory protein (GCKR) locus, has been previously associated with diabetes. The relationship between C3 levels and the GCKR locus was replicated in the European Genetic Database cohort., Conclusions: Plasma concentration of C3 is a risk marker for incidence of diabetes. The results suggest that this association could, in part, be explained by pleiotropic effects related to the GCKR gene., (Copyright © 2017 Endocrine Society)

Aims: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population., Methods: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption., Results: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (<5 g per day) had significantly lower common CIMT values than those consuming >10 g per day, after adjusting for a range of confounding factors., Conclusion: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT., (© The Author 2017. Medical Council on Alcohol and Oxford University Press.)

Background The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers. Objectives This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes. Methods MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors. Results Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation ( n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86-2.27) and stroke from all causes ( n = 195; HR 1.30; 95% CI 1.12-1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25-2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68). Conclusion High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.

Background: The pathophysiology of myocardial infarction (MI) may differ depending on whether it occurs early or late in life. We tested the hypothesis that risk factor pattern differs according to the age at MI., Methods: We performed a matched case-control study in the population-based Malmö Preventive Project (n = 33 346), where 3687 individuals developed MI during 22 ± 7 years of follow-up (=cases). The cases were divided into quartiles (Q1-Q4) according to age at event and were assigned two matched controls free from MI during follow-up. We used conditional logistic regression to assess relationship between risk factors at baseline and case status within quartiles of age at incident MI., Results: The median (range) age (years) at incident MI in Q1 was 52.9 (37.0-57.1), Q2 60.8 (57.1-63.6), Q3 66.6 (63.6-69.7), and Q4 73.5 (69.7-84.0). The odds ratio (95% CI) for incident MI associated with 1 SD increase of baseline cholesterol decreased with age of MI and was 1.68 (1.50-1.87) for Q1, 1.43 (1.28-1.61) for Q2, 1.27 (1.14-1.42) for Q3, and 1.08 (0.98-1.19) for Q4. Similarly, family history of MI had a stronger relationship with MI in Q1 than with MI in Q4 of MI age, whereas smoking displayed a U-shaped relationship. Exposure to the remaining risk factors did not differentially affect MI occurring at different age spans., Conclusion: Exposure to cholesterol and family history of MI more strongly predicts onset of MI at younger ages, suggesting that MI in younger subjects is preceded by a different risk factor pattern than MI presenting in older subjects., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: Recently, imbalance in the vasopressin (AVP) system, measured as elevated levels of copeptin (the C-terminal part of the AVP pro-hormone) in plasma, was linked to the development of abdominal obesity and diabetes mellitus (DM). Here, we aim to investigate if the genetic variation of the human AVP receptor 1b gene (AVPR1B) is associated with measures of obesity and DM., Design: Malmö Diet and Cancer study (MDC) is a population-based prospective cohort examined 1991-1996., Methods: Four tag single nucleotide polymorphisms (SNPs: rs35810727, rs28373064, rs35439639, rs35608965) of AVPR1B were genotyped in the cardiovascular cohort (n=6103) of MDC (MDC-CC) and associated with measures of obesity and DM. Significant SNPs were replicated in another 24 344 MDC individuals (MDC replication cohort)., Results: In MDC-CC, the major allele of rs35810727 was associated with elevated BMI (β-coefficient ± s.e.m.; 0.30 ± 0.14, P=0.03) and waist (0.78 ± 0.36, P=0.03) after age and gender adjustment. The association with BMI was replicated in the MDC replication cohort (0.21 ± 0.07, P=0.003), whereas that with waist was not significant. In MDC-CC there was no association between the major allele of rs35810727 and DM, but in the complete MDC cohort (n=30 447) the major allele of rs35810727 was associated with DM (OR (95% CI); 1.10 (1.00-1.20), P=0.04)., Conclusions: Genetic variance of AVPR1B contributes to overweight. Furthermore, our data indicate a link between AVPR1B variance and DM development. Our data point at a relationship between the disturbance of the pharmacologically modifiable AVP system and the body weight regulation., (© 2016 The authors.)

Background: Obesity is the major modifiable risk factor for diabetes. This study investigated the incidence of diabetes in relation to multiple anthropometric measures., Methods: Body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), waist-hip ratio (WHR) and body fat percentage (BF %) were measured among 26,604 subjects (aged 45-73 years) without history of diabetes from the Malmö Diet and Cancer cohort., Results: During 14 years of follow-up, 2935 subjects (1519 men, 1416 women) were diagnosed with diabetes. In men, incidence of diabetes was 24.1 and 4.0 per 1000 person-years comparing the fourth vs. first quartile of WHtR. The multivariate adjusted hazard ratios (HR; fourth vs first quartile) were 6.00 [95% confidence interval (CI): 5.02-7.16) for WHtR, 5.95 (CI: 4.96-7.14) for WC, 5.19 (CI: 4.38-6.15) for BMI, 4.71 (CI: 3.96-5.60) for WHR and 3.21 (CI: 2.75-3.76] for BF%. For women, incidence of diabetes was 15.1 and 1.4 per 1000 person-years for fourth vs first quartile of WHtR (HR: 10.19, CI: 8.10-12.82). HR was 9.16 (CI: 7.40-11.33) for WC, 6.42 (CI: 5.27-7.81) for BMI, 6.75 (CI: 5.52-8.25) for WHR and 5.39 (CI: 4.42-6.57) for BF%. Model discrimination was marginally increased when WC, WHtR or WHR was used in combination with BMI., Conclusion: All measures of obesity were associated with substantially increased incidence of diabetes. Abdominal obesity was associated with higher incidence rates in men than in women, but in terms of relative risks the relationships were stronger in women. The combination of BMI and abdominal obesity measures had stronger association with diabetes than BMI alone., (© The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: It is unclear which anthropometric measure is most useful for assessment of the cardiovascular risk. We investigated the association between different anthropometric measures and risk of heart failure (HF) hospitalization., Methods: BMI, waist-hip ratio (WHR), waist circumference (WC), body fat percentage (BF%), weight and height were measured among 26,653 subjects (aged 45-73 years) without history of myocardial infarction (MI), stroke or HF from the Malmö Diet and Cancer cohort at baseline in 1991-96. Incidence of HF hospitalizations was monitored during a mean follow-up of 15 years., Results: Seven hundred and twenty-seven subjects were hospitalized with HF as primary diagnosis, of whom 157 had an MI before or concurrent with the HF. After adjustment for potential confounding factors, the hazard ratios of HF hospitalization (fourth vs. first sex-specific quartile) were 1.80 (95% CI: 1.45-2.24) for BMI, 1.87 (1.50-2.34) for WC, 1.77 (1.43-2.19) for WHR, 1.35 (1.09-1.68) for BF%, 1.93 (1.57-2.39) for weight and 1.18 (0.96-1.44) for height. Significant interactions between BMI and WC and WHR, respectively, were observed, and the joint exposure of high BMI and high WC or high WHR further increased the risk. The results were similar in secondary analyses, i.e., excluding incident HF with previous MI during the follow-up., Conclusion: Our results support the view that raised BMI, WC, WHR or BF% increases the risk of HF hospitalization. The joint exposure of high BMI and high WHR or high WC further increased the risk in an additive way.

Background: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS., Design: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events., Methods: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events., Results: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women., Conclusions: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Aims: We recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences., Methods and Results: We performed a matched case-control study derived from the population-based Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.72-2.22), 1.96 (1.07-3.60), and 2.20 (1.12-4.31) (Ptrend = 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm(2) (Ptrend = 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.05-10.4), 4.24 (1.36-13.3), and 4.86 (1.47-16.1) (Ptrend = 0.011), respectively., Conclusion: This study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility.

Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown., Methods and Results: A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥ 20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04)., Conclusion: The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.

Context: The cardiac natriuretic peptides are involved in blood pressure regulation, and large cross-sectional studies have shown lower plasma levels of N-terminal pro-natriuretic peptide levels [N-terminal atrial natriuretic peptide (N-ANP) and N-terminal brain natriuretic peptide (N-BNP)] in patients with insulin resistance, obesity, and diabetes., Objective: In this study, we prospectively tested whether plasma levels of mid-regional ANP (MR-ANP) and N-BNP predict new-onset diabetes and long-term glucose progression., Design, Setting, and Patients: MR-ANP and N-BNP were measured in 1828 nondiabetic individuals of the Malmö Diet and Cancer cohort (mean age 60 yr; 61% women) who subsequently underwent a follow-up exam including an oral glucose tolerance test after a median follow-up time of 16 yr. Logistic regression was used to adjust for covariates., Results: During follow-up, 301 subjects developed new-onset diabetes. After full multivariate adjustment, MR-ANP was significantly inversely associated with incident diabetes (OR = 0.85; 95% CI = 0.73-0.99; P = 0.034) but not N-BNP (OR = 0.92; 95% CI = 0.80-1.06; P = 0.262). In fully adjusted linear regression models, the progression of fasting glucose during follow-up was significantly inversely related to baseline levels of MR-ANP (P = 0.004) but not N-BNP (P = 0.129). Quartile analyses revealed that the overall association was mainly accounted for by excess risk of incident diabetes in subjects belonging to the lowest quartile of MR-ANP. After full adjustment, the odds ratio for incident diabetes in the bottom compared with the top quartile of MR-ANP was 1.65 (OR = 1.08-2.51, P = 0.019) and 1.43 (OR = 1.04-1.96, P = 0.027) compared with all other subjects., Conclusion: Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.

Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.

Context: Arginine vasopressin (AVP) is known to affect liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We previously showed that high copeptin, the stable C-terminal fragment of AVP prohormone, is independently associated with hyperinsulinemia and future development of diabetes mellitus., Objective: The objective of the study was to examine whether plasma copeptin is associated with components of the metabolic syndrome (MetS) independently of insulin, diabetes mellitus, and environmental factors., Design, Setting, and Participants: This was a cross-sectional, population-based sample of 4742 subjects, aged 46-68 yr, 60% women, in Malmö, Sweden., Main Outcome Measure: Using multivariable logistic and linear regression, plasma copeptin was associated with components of the MetS., Results: Copeptin quartile (lowest quartile as reference) was, after adjustment for age, sex, insulin, and diabetes mellitus, associated with hypertension (odds ratios 1.04, 1.07, 1.31; P = 0.004), abdominal obesity (odds ratios 1.21, 1.16, 1.57; P = 0.002), obesity (odds ratios 1.25, 1.15, 1.49; P = 0.01), top quartile of c-reactive protein (odds ratios 1.11, 1.13, 1.32; P = 0.007), and MetS (adjusted for age and sex only) (odds ratios 1.53, 1.77, 1.86; P < 0.001). High copeptin levels were significantly associated with high fat intake, low physical activity, and borderline significantly associated with low socioeconomic status. The association between copeptin and components of the MetS was not affected after adjustment for these environmental factors., Conclusions: Our data suggest that increased activity of the AVP system is a unifying factor in the MetS and point to a new pharmacologically modifiable system of potential importance in the treatment of MetS and prevention of cardiovascular disease.

Aims: A higher intake of fruits and vegetables has been associated with a lower risk of ischaemic heart disease (IHD), but there is some uncertainty about the interpretation of this association. The objective was to assess the relation between fruit and vegetable intake and risk of mortality from IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heart study., Methods and Results: After an average of 8.4 years of follow-up, there were 1636 deaths from IHD among 313 074 men and women without previous myocardial infarction or stroke from eight European countries. Participants consuming at least eight portions (80 g each) of fruits and vegetables a day had a 22% lower risk of fatal IHD [relative risk (RR) = 0.78, 95% confidence interval (CI): 0.65-0.95] compared with those consuming fewer than three portions a day. After calibration of fruit and vegetable intake to account for differences in dietary assessment between the participating centres, a one portion (80 g) increment in fruit and vegetable intake was associated with a 4% lower risk of fatal IHD (RR = 0.96, 95% CI: 0.92-1.00, P for trend = 0.033)., Conclusion: Results from this large observational study suggest that a higher intake of fruits and vegetables is associated with a reduced risk of IHD mortality. Whether this association is causal and, if so, the biological mechanism(s) by which fruits and vegetables operate to lower IHD risks remains unclear.

Background: The presence of orthostatic hypotension (OH) predicts all-cause mortality and incident cardiovascular disease. Whether or not OH is associated with the development of heart failure (HF) remains unknown., Methods: In this Swedish population-based prospective study (the Malmö Preventive Project), the incidence of HF in relation to baseline OH, defined as decrease in systolic (SBP) ≥20 mm Hg and/or diastolic blood pressure (DBP) ≥10 mm Hg upon standing, was studied in 32,669 middle-aged individuals (68.2% men; mean age, 45.6 ± 7.4 years) over a mean follow-up period of 24 years., Results: At baseline, 1,991 (6.1%) participants were found to have OH. During follow-up, 1,293 persons (4.0%, mean age at presentation: 67.9 ± 7.9 years) were hospitalized for HF, 912 (2.8%) of whom without previous or concurrent myocardial infarction (MI) ("nonischemic HF"). Among those who had OH, the corresponding numbers were 6.5% (n = 129) and 4.6% (n = 92), respectively. In multivariable Cox proportional hazard models, taking conventional HF risk factors into account, OH was associated with both all-cause and "nonischemic" HF events (hazard ratio (HR): 1.22, 1.01-1.46, and 1.31, 1.05-1.63, respectively). The association between OH and HF was more pronounced in younger (aged <45 years) than older individuals (2.05; 1.31-3.22 vs. 1.12, 0.92-1.38, respectively, P < 0.001 for interaction between age and OH on incident HF)., Conclusions: The presence of OH among middle-aged adults predicts long-term incidence of HF hospitalizations independently of conventional risk factors. Our findings add to the available data indicating that OH is a potential independent cardiovascular risk factor, especially with regard to younger individuals and nonischemic HF.

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: There are no previous studies investigating when and where those who die pre-hospitally after an AMI paid their last visit to medical care., Methods and Results: Incidence of AMI, pre-hospital and 28-day case fatality rates were monitored over 13 years of follow-up, in relation to sex-specific quartiles of annual income in all inhabitants aged 40-64 years in Malmö, Sweden. Both incidence and short-term case fatality were inversely related to income. In all, 60-70% of all deaths within 28 days after the AMI were pre-hospital deaths. As compared with the lowest income group, the highest income group had lower odds of pre-hospital death with an age- and time-to-event-adjusted odds ratio of 0.5 (95% CI 0.4-0.8) for men and 0.3 (95% CI 0.1-0.6) for women. On the other hand, while 72% of those in the lowest two income groups had paid a visit to the medical services during the three months before death, only 59% had done so in the two highest income groups (P < 0.05)., Conclusions: Poor socioeconomic circumstances increase the risk of pre-hospital death after an AMI. Of the pre-hospital deaths, the proportion who had visited the medical services during the 3 months preceding their AMI was higher among those from lower income groups. However, many of those suffering a pre-hospital death had visited clinics that normally do not treat coronary symptoms. If more patients were identified at an earlier stage this might increase the number of patients reaching hospital alive.

Background: The role of inflammation as part of the explanation of socioeconomic differences in carotid atherosclerosis has not been specifically investigated., Methods and Results: The associations between socioeconomic position (SEP), C-reactive protein (CRP), and preclinical carotid atherosclerosis were investigated in a general population sample of 3921 middle-aged Swedish men and women. Common carotid intima-media thickness (IMT) and presence of carotid plaque (focal IMT > 1.2 mm) were determined by B-mode ultrasound. The results showed that low SEP was associated with increased levels of CRP, independently of established risk factors. Furthermore, common carotid IMT increased with increasing CRP-levels. Presence of carotid plaque increased with increasing CRP-levels in men, but not in women. While the socioeconomic differences in carotid IMT were weak, there were associations between low educational level and carotid plaque prevalence with an age- and sex-adjusted odds ratio (OR) of 1.39 (95% CI: 1.21, 1.59). A similar association was seen for having a manual occupation, OR = 1.23 (95% CI: 1.07, 1.42). The age- and sex-adjusted absolute differences in carotid plaque prevalence were 9% with regard to educational level and 7% with regard to occupational status. Adjustment for CRP caused only a minor attenuation of the association between SEP and carotid atherosclerosis., Conclusions: The association between SEP and carotid atherosclerosis as measured by carotid IMT and carotid plaque could only to a minor extent be referred to differences in low grade inflammation as measured by CRP.

Objectives: To explore the effect of social characteristics of residential areas on carotid atherosclerosis prevalence., Methods and Results: The associations among area social characteristics and B-mode ultrasound determined carotid plaque-score (a semi-quantitative scale measuring the degree of atherosclerosis in the carotid bifurcation area) were cross-sectionally investigated in a general population sample of 4033 men and women. Area socioeconomic circumstances were described through a social deprivation index calculated from migration rate, percentage residents with foreign citizenship among those with foreign background, dependency on social welfare support, and employment rate. Living in socially deprived areas was associated with an increased carotid plaque-score in both men (P for trend = 0.004) and women (P for trend = 0.007). These associations were only slightly reduced after adjustment for individual level indicators with a decrease of the absolute mean difference in carotid plaque-score between worse-off and better-off areas of 9% for men and 13% for women, whereas adjustment for risk factors turned the trend non-significant in women, however, not in men., Conclusions: Those living in socially deprived areas in general had more extensive carotid atherosclerosis. However, in these areas there were a substantial number of individuals with low degrees of carotid atherosclerosis and vice versa. Thus, with regard to conceptual ideas of causal inference, the social characteristics of an area seem to be associated with the prevalence of carotid atherosclerosis. However, with regard to benefits of prevention, focusing on geographical areas would probably give a restricted benefit, where only some high-risk individuals would be reached.

Background: In Malmö approximately 250,000 citizens live in 17 administrative areas with substantial socioeconomic differences. At the single centre for arterial reconstruction, Malmö University Hospital, all procedures are registered prospectively., Methods: Between 1987 and 2002, 1832 Malmö citizens underwent reconstruction for peripheral arterial disease, either intermittent claudication (IC) or critical leg ischaemia (CLI). A socioeconomic score based on migration rate, percentage of residents with foreign citizenship/residents with foreign background, social welfare support dependency and unemployment rate has previously been developed and validated for each area. The relationship between socioeconomic score and area-specific standardized morbidity ratios (SMRs) after vascular reconstruction was analysed by population-weighted linear regression., Results: The mean incidence of vascular reconstruction was 76 (range 27-106) per 100,000 person years. Age- and sex-adjusted SMRs ranged from 0.57 to 1.39. A strong correlation between SMR and socioeconomic score was found overall (R=0.63; P=0.007), in men (R=0.63; P=0.007) and in women (R=0.58; P=0.039), and for IC (R=0.58; P=0.015) and CLI (R=0.58; P=0.015)., Conclusion: In an urban population with similar access to medical care, vascular reconstruction rates varied substantially. High-rate areas were characterized by inferior socioeconomic circumstances and a higher prevalence of smoking, hypertension and obesity., (Copyright (c) 2006 British Journal of Surgery Society Ltd.)

Background: In order to better understand the role of work environment in the earlier stages of the cardiovascular disease process, we wanted to investigate the influence of work-related psychosocial factors on preclinical atherosclerosis., Methods: Cross-sectional data was used to examine the association between psychological job demands, job decision latitude, and carotid atherosclerosis in 2658 vocationally-active Swedish men and women, ages 46-65, from the general population. Odds ratios of carotid plaque prevalence and carotid artery intima-media thickness (IMT), determined by B-mode ultrasound, were estimated across combinations of job demands and decision latitude., Results: Women in job situations with high demands and low decision latitude ('job strain') showed a high plaque prevalence odds (odds ratio [OR] = 1.68, 95% CI: 1.14, 2.48), and a thicker IMT in the carotid bifurcation area (mean difference: 0.15 mm, 95% CI: 0.07, 0.23) compared with women in job situations with low demands and high decision latitude ('relaxed'). Adjustment for covariates only slightly reduced the magnitude of these associations. No such associations were seen in men. However, women in job situations with high demands and high decision latitude ('active') also showed high odds for carotid plaque, and a thicker IMT in the carotid bifurcation, compared with women in 'relaxed' job situations. In men, those in 'active' job situations had a low carotid plaque prevalence odds, while IMT in the carotid bifurcation did not differ from those in 'relaxed' job situations. Results showed only weak associations with IMT in the common carotid artery (CCA) in both men and women., Conclusion: The specific hypothesis that high job demands interact synergistically with low decision latitude in the development of carotid atherosclerosis could not be supported in this study, neither in men nor in women. Instead a more complex pattern of interaction between job demands and decision latitude was shown.

This study examined the relations between food patterns and five components of the metabolic syndrome in a sample of Swedish men (n = 2,040) and women (n = 2,959) aged 45-68 years who joined the Malmö Diet and Cancer study from November 1991 to February 1994. Baseline examinations included an interview-administered diet history, a self-administered questionnaire, blood pressure and anthropologic measurements, and blood samples donated after an overnight fast. Cluster analysis identified six food patterns for which 43 food group variables were used. Logistic regression analysis was used to examine the risk of each component (hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, and central obesity) and food patterns, controlling for potential confounders. The study demonstrated relations, independent of specific nutrients, between food patterns and hyperglycemia and central obesity in men and hyperinsulinemia in women. Food patterns dominated by fiber bread provided favorable effects, while food patterns high in refined bread or in cheese, cake, and alcoholic beverages contributed adverse effects. In women, food patterns dominated by milk-fat-based spread showed protective relations with hyperinsulinemia. Relations between risk factors and food patterns may partly depend on gender differences in metabolism or food consumption and on variations in confounders across food patterns.

A personal diary may be more appropriate than a questionnaire for assessing self-reported current use of hormone therapy (estrogens, progestagens, or their combination); however, use of a questionnaire is more feasible and less expensive. The authors compared both methods for 16,060 Swedish women aged 45-73 years from the Malmo Diet and Cancer Study (baseline, 1991-1996). In a reliability analysis, the authors investigated the agreement (kappa value) between the questionnaire and the diary regarding current hormone therapy use (yes vs. no), studying the ability to replicate results whether or not they were correct. They also explored associations between discrepancy and individual characteristics. A validity analysis was conducted to determine whether use of the questionnaire achieved an outcome without systematic error (i.e., high specificity and sensitivity); the personal diary was considered the "gold standard." Agreement between both methods was high: 95.5% (kappa = 0.840). The sensitivity was 84.9% and the specificity 97.7%. Higher body mass index and being a widow were associated with agreement, whereas age (50-59 years), use of anxiolytics/hypnotics or opiates, high alcohol consumption, past smoking, and higher educational level were associated with discrepancy. Compared with a personal diary, a simple self-administered questionnaire is a valid method for assessing current use of hormone therapy.

The associations among educational level, occupational status, and atherosclerosis were investigated during 1992-1994 in a general population sample of 4,176 Swedish men and women. Carotid artery intima-media thickness (IMT) and carotid stenosis were determined by B-mode ultrasound. Socioeconomic differences in mean carotid IMT and odds ratios for carotid stenosis prevalence were estimated. In women, the associations among educational level, occupational status, and IMT were weak. In men, there was no association between education and IMT, while low occupational status was associated with a thicker IMT. Women with low education had an increased odds of carotid stenosis compared with women with high education (odds ratio (OR) = 2.04, 95% confidence interval (CI): 1.53, 2.73), while this pattern was weaker among men. Women in manual occupations had an increased odds of carotid stenosis compared with women in high- or medium-level nonmanual occupations (OR = 1.75, 95% CI: 1.29, 2.36), which could not be seen among men. After adjustment for risk factors, the association between IMT and occupational status in men disappeared, while the associations among educational level, occupational status, and carotid stenosis in women persisted. The results imply that the atherosclerotic process is associated with socioeconomic status in both sexes, and they also indicate the possibility of sex differences in the mechanisms connecting socioeconomic status to atherosclerosis.

Aim: To assess to what extent do frequent or complex ventricular arrhythmias, detected during 24 h ambulatory electrocardiographic recording (ECG), influence prognosis with regard to survival and incidence of ischaemic heart disease., Methods and Results: The study subjects were the 456 randomly selected men born in 1914, the population-based cohort study of 1982-83, in Malmö, Sweden. The main outcome measures were total mortality and incidence of cardiac event (myocardial infarction and death from ischaemic heart disease). Frequent or complex ventricular arrhythmias (Lown classes 2-5) were detected in 49% of the men with (n = 77), and in 35% of those without, a history of myocardial infarction or angina pectoris at baseline, P = 0.019. Independent of clinically evident coronary artery disease at baseline, and after adjustment for traditional atherosclerotic risk factors and use of digitalis or beta-blocker therapy, frequent or complex ventricular arrhythmias were associated with an increased mortality from ischaemic heart disease (relative risk (RR), 2.1; 95% confidence interval (CI), 1.2-3.9) and an increased cardiac event rate (RR, 1.6; 95% CI, 1.0-2.5)). Men free from both ischaemic-type ST depression and frequent or complex ventricular arrhythmias (used as the control group) had the lowest ischaemic heart disease death rate, 5.9 per 1000 person-years. The combination of ST depression and frequent or complex ventricular arrhythmias was associated with an ischaemic heart disease death rate of 20.9 per 1000 person-years. The cardiac event rate in these two groups was 15.6 and 76.1 per 1000 person-years, respectively (adjusted RR, 2.3; CI, 1.1-4.6)., Conclusions: In elderly men without a history of myocardial infarction and angina pectoris, frequent or complex ventricular arrhythmias during ambulatory ECG recording is associated with an increased incidence of myocardial infarction and mortality. Men who, during ambulatory ECG recording, also demonstrate ST-segment depression have an even less favourable prognosis.

Three-hundred and ninety-four 68-year-old men, representing 60.3% of a cohort of men born in 1914, were examined with ambulatory ECG during 24 h in 1982-83. Ninety-eight (24.8%) men had one or more episodes of ischaemic type ST segment depression (greater than or equal to 0.10 mV), 79 of whom had no history of previous ischaemic heart disease (IHD). During 63 months follow-up, 17 of the 98 suffered a cardiac event, i.e. fatal or non-fatal myocardial infarction (MI) or death due to chronic IHD. The objective of this study was to assess the influence of psychosocial factors, such as social network and social support, on cardiac event rate in men with ischaemic ST segment depression. A higher risk was found among men with little material and informational support (i.e. access to practical services and material resources and access to guidance, advice and information (crude relative risk 4.8; 95% CI; 1.6-14.8) and men with low availability of emotional support (i.e. opportunity for care, encouragement of personal value and feelings of confidence and trust) (crude relative risk 4.3; 95% CI: 1.4-13.3). This association was independent of history of IHD and other known risk factors for myocardial infarction (MI).

'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.