Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association ...of low levels of lead exposure with kidney function and kidney disease.
Prospective population-based cohort.
4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012).
Blood lead concentrations in quartiles (Q1-Q4) at baseline.
Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry.
Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data.
At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) μg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m2 (based on creatinine) and 24mL/min/1.73m2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined.
Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding.
Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.
Increased red cell distribution width (RDW) has been related to poor prognosis in patients with cardiovascular disease, and is a predictor of cardiovascular mortality in the general population. The ...purpose of the present study was to investigate if RDW is associated with increased incidence of stroke and its subtypes in individuals from the general population.
Red cell distribution width was measured in 26,879 participants (16,561 women and 10,318 men aged 45-73 years) without history of coronary events or stroke, from the population-based Malmö Diet and Cancer Study. Incidences of total stroke and stroke subtypes over a mean follow-up of 15.2 years were calculated in relation to sex-specific quartiles of RDW. The presence of carotid plaque and intima-media thickness, as assessed by ultrasound, was studied in relation to RDW in a randomly selected subcohort (n = 5,309).
Incidences of total stroke (n = 1,869) and cerebral infarction (n = 1,544) were both increased in individuals with high RDW. Hazard ratios (HRs) in the highest compared to the lowest quartile were 1.31 for total stroke (95% confidence interval CI: 1.11-1.54, p for trend = 0.004) and 1.32 for cerebral infarction (95% CI: 1.10-1.58, p for trend = 0.004) after adjustment for stroke risk factors and hematological parameters. The adjusted HR for intracerebral hemorrhage (n = 230) was 1.44 (95% CI: 0.90-2.30) and the HR for subarachnoid hemorrhage (n = 75) was 0.94 (95% CI: 0.43-2.07), in the highest compared to the lowest quartile of RDW. Red cell distribution width was positively associated with intima-media thickness of the common carotid artery (p for trend = 0.011).
Red cell distribution width in the highest quartile was associated with increased incidence of total stroke and cerebral infarction. There was no significant association between RDW and incidence of intracerebral or subarachnoid hemorrhage.
Objectives The purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of ...multiple biomarkers reflecting diverse pathophysiological pathways. Background Heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited. Methods In 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin. Results During a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio HR: 1.63 per SD, 95% confidence interval CI: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c -statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification. Conclusions Conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.
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.
•It has been unclear if low-level lead exposure increases blood pressure.•In this population-based cohort (N=4452) the mean blood lead was 28µg/L.•Higher blood lead was associated with higher systolic and diastolic blood pressure.•Lead was associated with hypertension at baseline, but not after 16 years.•Low-level lead exposure increases blood pressure and maybe the risk of hypertension.
Community screening to guide preventive interventions for acute aortic disease has been recommended in high-risk individuals. We sought to prospectively assess risk factors in the general population ...for aortic dissection (AD) and severe aneurysmal disease in the thoracic and abdominal aorta.
We studied the incidence of AD and ruptured or surgically treated aneurysms in the abdominal (AAA) or thoracic aorta (TAA) in 30 412 individuals without diagnosis of aortic disease at baseline from a contemporary, prospective cohort of middle-aged individuals, the Malmö Diet and Cancer study. During up to 20 years of follow-up (median 16 years), the incidence rate per 100 000 patient-years at risk was 15 (95% CI 11.7 to 18.9) for AD, 27 (95% CI 22.5 to 32.1) for AAA, and 9 (95% CI 6.8 to 12.6) for TAA. The acute and in-hospital mortality was 39% for AD, 34% for ruptured AAA, and 41% for ruptured TAA. Hypertension was present in 86% of individuals who subsequently developed AD, was strongly associated with incident AD (hazard ratio HR 2.64, 95% CI 1.33 to 5.25), and conferred a population-attributable risk of 54%. Hypertension was also a risk factor for AAA with a smaller effect. Smoking (HR 5.07, 95% CI 3.52 to 7.29) and high apolipoprotein B/A1 ratio (HR 2.48, 95% CI 1.73 to 3.54) were strongly associated with AAA and conferred a population-attributable risk of 47% and 25%, respectively. Smoking was also a risk factor for AD and TAA with smaller effects.
This large prospective study identified distinct risk factor profiles for different aortic diseases in the general population. Hypertension accounted for more than half of the population risk for AD, and smoking for half of the population risk of AAA.
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.
Background High parity has been suggested to increase risk of maternal cardiovascular disease independent of body mass index measured after childbearing. Pregnancy is, however, associated with ...persistent weight gain and metabolic changes that, independent of parity, increase the risk of cardiovascular disease. It could therefore be questioned if high parity independently increases the risk of cardiovascular disease or if this association may be confounded, mediated, or modified by other parity-related factors. Objective We sought to investigate the association between parity and risk of cardiovascular disease, and secondary outcomes in terms of myocardial infarction and cerebral infarction, with particular focus on potential mediation by anthropometric measures and effect modification by lactation. Study Design We used data from 16,515 female participants (age 44.5-73.6 years) of the population-based Malmö Diet and Cancer Study with baseline examination from 1991 through 1996. The Malmö Diet and Cancer Study was followed up throughout 2010, with a median follow-up of 15.8 years. We used Cox proportional hazards model to examine the association between parity and cardiovascular disease. Results Adjusted for age and other potential confounders, grand multiparous women (≥5 children) had an increased risk of cardiovascular disease (hazard ratio, 1.60; 95% confidence interval, 1.20–2.14), myocardial infarction (hazard ratio, 1.68; 95% confidence interval, 1.15–2.45), and cerebral infarction (hazard ratio, 1.74; 95% confidence interval, 1.18–2.58) compared to women with 2 children. Additional adjustment for baseline body mass index and weight change since age 20 years attenuated the risk, but the increased risk for cardiovascular disease (hazard ratio, 1.38; 95% confidence interval, 1.02–1.87) and myocardial infarction (hazard ratio, 1.53; 95% confidence interval, 1.04–2.26) in grand multiparous women remained significant. Models stratified by lactation time showed that risk was only raised in grand multiparous women who had a mean lactation time of <4 mo/child. In sensitivity analyses excluding women with a history of diabetes at baseline, risk estimates for grand multiparous women became nonsignificant in the full model. Conclusion Part of the increased risk of cardiovascular disease and myocardial infarction in grand multiparous women seems to be mediated by weight gain and potentially by higher likelihood of type 2 diabetes mellitus. Lactation may modify the increased risk of grand multiparity in that longer duration might offset the cardiovascular disease risk.
The validity of atrial fibrillation (AF) diagnoses in national registers for use as endpoints in prospective studies has not been evaluated. We studied the validity of AF diagnoses in Swedish ...national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers. Our study included the 30,447 individuals (age 44-73) who attended baseline visits in 1991-1996 of the Malmö Diet and Cancer study. Individuals with a first AF diagnosis were identified by record linkage with national registers. A subset of cases was randomly selected for validation by examination of electrocardiograms and patient records. Electrocardiograms were available in 98% of the validation sample (95% definitive AF, 3% no AF). The 2% with ECGs unavailable had probable AF. Baseline AF prevalence was 1.3%, higher in men and increased with age. During 11.2 years of follow-up 1430 first AF diagnoses occurred. Risk factors were age, hypertension, BMI, diabetes, history of heart failure, history of myocardial infarction and, in men but not women, current smoking. The strongest risk factors were history of heart failure (hazard ratio men 4.5, women 8.7) and myocardial infarction (hazard ratio men 2.0, women 1.8). The largest population attributable risks were observed for hypertension (men 38%, women 34%) and obesity (men 11%, women 10%). In conclusion, case misclassification of AF in national registers is small, indicating feasibility of use in prospective studies. Hypertension and obesity account for large portions of population risk in middle-aged individuals with low prevalence of manifest cardiac disease.
Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are ...based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.
Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.
The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
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.
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