Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. We aimed to examine the effects of environmental exposure to lead in a large population-based sample. We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46-67 years) living in Malmö, Sweden, in 1991-1994. Blood pressure was measured using a mercury sphygmomanometer after 10min supine rest. Hypertension was defined as high systolic (≥140mmHg) or diastolic (≥90mmHg) blood pressure and/or current use of antihypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multivariable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. At baseline, mean blood pressure was 141/87mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28µg/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1-2mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1-1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a half-life of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. Low-level lead exposure increases blood pressure and may increase the risk of hypertension.

OBJECTIVE Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes. RESEARCH DESIGN AND METHODS The study population included participants from the Malmö Diet and Cancer cardiovascular cohort, using measurements from the 2007–2012 reexamination as baseline. Arterial stiffness was evaluated by measuring c-f PWV (SphygmoCor). After excluding participants with prevalent diabetes (according to measurements of fasting glucose, oral glucose tolerance tests, and physician’s diagnoses), the final study population consisted of 2,450 individuals (mean age = 71.9 ± 5.6 years). Incidence of diabetes was followed by linkage to local and national diabetes registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to the tertiles of c-f PWV, adjusted for potential confounders. RESULTS During a mean follow-up of 4.43 ± 1.40 years, 68 (2.8%) participants developed diabetes. Crude incidence of diabetes (per 1,000 person-years) was 3.5, 5.7, and 9.5, respectively, for subjects in the first, second, and third tertiles of c-f PWV. After adjusting for potential confounders, the hazard ratio of diabetes was 1.00 (reference), 1.83 (95% CI 0.88–3.8), and 3.24 (95% CI 1.51–6.97), respectively, for the tertiles of c-f PWV (P for trend = 0.002). CONCLUSIONS Increased c-f PWV is associated with increased incidence of diabetes, independent of other risk factors. These results suggest that increased arterial stiffness is an early risk marker for developing diabetes.

Aims Red cell distribution width (RDW) has been associated with cardiovascular disease, but the relation to heart failure (HF) is unclear. We investigated the association between RDW and incidence of first hospitalization due to HF in a population‐based cohort. Methods and results Red cell distribution width was measured in 26 784 subjects (aged 45–73 years, 61% women), without history of myocardial infarction (MI), stroke or HF, who participated in the Malmö Diet and Cancer study during 1991–1996. Incidence of HF was identified from the national Swedish hospital discharge register during a mean follow‐up of 15 years and studied in relation to RDW. During follow‐up, 773 subjects (55% men) were hospitalized due to HF, of whom 166 had an MI before or concurrent with the HF. After adjustment for potential confounding factors (including history of coronary revascularization, biological, lifestyle, and socio‐economic factors), the hazard ratios (HR) for HF were 1.47 (95% CI: 1.14–1.89) in the top compared with the bottom quartile of RDW (P for trend 0.005), censoring subjects with incident MI before HF. The results were similar when all hospitalized HF cases were included (HR: 1.33, 1.07–1.66), (P for trend 0.020). After additional adjustment for N‐terminal pro‐B‐type natriuretic peptide, cystatin C and high‐sensitive C‐reactive protein in a randomly selected subcohort (n= 4761), HR was 1.64 (CI: 0.90–3.00) comparing the top vs. bottom quartile of RDW. Conclusion Red cell distribution width was found to be associated with long‐term incidence of first hospitalization due to HF among middle‐aged subjects.

Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. A population sample of 4639 Swedish middle-aged women and men was examined in 1991-1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6-2.2) after adjustment for sex and, age; 1.4 (1.1-1.8) after additional adjustment for smoking status; 1.4 (1.1-1.7) after the addition of education level and life style factors; 1.3 (1.03-1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0-2.1) and 1.4 (0.9-2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure.

Smoking is a strong risk factor for cardiovascular disease (CVD) and causes exposure to cadmium, which is a pro-atherosclerotic metal. Cadmium exposure has also been shown to increase the risk of CVD, even after adjustment for smoking. Our hypothesis was that part of the risk of CVD in smokers may be mediated by cadmium exposure from tobacco smoke. We examined this hypothesis in a mediation analysis, trying to assess how much of the smoking-induced CVD risk could be explained via cadmium. We used prospective data on CVD (incidence and mortality) in a Swedish population-based cohort of 4304 middle-aged men and women (the Malmö Diet and Cancer Study). Blood cadmium was analyzed in base-line samples from 1991, and clinical events were followed up for 16–19 years based on registry data. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on CVD. Survival was analyzed by the accelerated failure time (AFT) model and the Aalen additive hazard model. The mean blood cadmium level in the study population was 0.43 μg/L (median 0.24 μg/L) and increased with recent and current smoking. As expected, shorter survival time (AFT model) and higher incidence rate (Aalen model) were found in current smokers for all CVD outcomes and this effect seemed to be partly mediated by cadmium. For the sum of acute myocardial infarction, bypass grafts and percutaneous coronary intervention, and death in ischemic heart disease, about half of the increased risk of such events in current smokers was mediated via cadmium, with similar results for the AFT and Aalen models. Cadmium plays an important role in smoking-induced CVDs. This provides evidence for mechanisms and is of importance for both individuals and policy makers.

Aims Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population‐based cohort. Methods and results Soluble urokinase plasminogen activator receptor was measured in 4530 subjects (aged 46–68 years, 61% women), who participated in the Malmö Diet and Cancer study during 1991–1996. Incident cases of HF and AF were identified from the Swedish hospital discharge register during a median follow‐up of 16.3 years. During follow‐up, 109 subjects (55% men) were diagnosed with new‐onset HF and 321 individuals (50% men) with AF. suPAR was significantly associated with increased plasma levels of NT‐proBNP (P < 0.001). suPAR was significantly associated with incidence of HF [hazard ratio (HR) for the third vs. first tertile 3.33, 95% confidence interval (CI) 1.91–5.81 after adjustment for age and sex; and HR 1.82, 95% CI 1.02–3.27, P for trend 0.018 after adjustment for conventional risk factors and biomarkers]. suPAR was significantly associated with incidence of AF, when adjusted for age and sex (HR 1.40, 95% CI 1.06–1.85). However, this relationship was non‐significant after adjustment for conventional risk factors and biomarkers. Conclusion Soluble urokinase plasminogen activator receptor was associated with increased plasma levels of NT‐proBNP and incidence of HF, but not with AF among middle‐aged subjects.