Red Cell Distribution Width (RDW) could be a risk factor for developing various chronic diseases, and seems to be a prognostic marker in patients with cardiovascular disease (CVD) or cancer. Our aim ...was to explore the association between RDW and all-cause and cause-specific mortality in a general population. RDW was measured in 27,063 participants (aged 45-73 years) from the population-based Malmö Diet and Cancer cohort. After a follow-up of 19.8 ± 5.5 years, Cox proportional hazards regression analysis was used to study the relationship between RDW and all-cause and cause-specific mortality, with adjustment for confounding factors. A total of 9388 individuals (4715 men and 4673 women) died during the follow up. High RDW was significantly associated with all-cause mortality (HR, 4
vs. 1
quartile: 1.34, 95%CI: 1.24-1.45), cancer mortality (HR: 1.27, 95%CI: 1.12-1.44), CVD mortality (HR: 1.39, 95%CI: 1.21-1.59), and respiratory disease mortality (HR: 1.47, 95%CI: 1.06-2.03). The C-statistic increased significantly from 0.732 to 0.737 when adding RDW to a model adjusted for age and sex. There was a significant interaction between RDW and BMI with respect to all-cause mortality. We concluded that RDW is associated with mortality and propose that high RDW is a significant, but non-specific marker of mortality risk in the general population.
Breathlessness is prevalent in the general population and may be associated with adverse health outcomes. This study aimed to evaluate the association of breathlessness with Chronic Obstructive ...Pulmonary Disease (COPD) events, cardiac events and all-cause mortality from middle-age throughout life.
Breathlessness was measured in 699, 55-year old men residing in Malmö, Sweden using modified Medical Research Council (mMRC). COPD events (hospitalisation, death or diagnosis) cardiac events and all-cause mortality was assessed using The Swedish Causes of Death Register and Hospital Discharge Register. Data was analyzed using Cox- and competing risks (Fine-Gray) regression analysis.
695 (99%) of 699 participants died and four emigrated during follow up. Eighty-seven (12%) had mMRC = 1 and 19 (3%) had mMRC≥2. Breathlessness was associated with COPD events; adjusted Sub-Hazard Ratio 2.1 (95% CI, 1.2-3.6) for mMRC = 1 and 7.5 (2.6-21.7) for mMRC ≥ 2 but not associated with cardiac events when adjusting for competing events and confounding. Breathlessness was associated increased all- cause mortality (Hazard Ratios of 1.4 (1.1-1.7) (mMRC = 1) and 3.4 (2.1-5.6) (mMRC ≥ 2)).
Breathlessness is associated with increased risk of COPD events and increase in all-cause mortality from age 55 until death.
Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and ...atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56–0.68), high diet quality (HR = 0.83, 95% CI 0.72–0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80–0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.
Vasopressin is a pleiotropic hormone that controls body fluid homeostasis. Vasopressin has also been proposed to be involved in erythropoiesis, thrombocyte activity and inflammation. However, whether ...increasing vasopressin is associated with changes in hematopoietic markers is not known. To evaluate this gap of knowledge we measured the vasopressin marker copeptin and markers of erythropoiesis (erythrocyte count, hemoglobin (Hb), red blood cell distribution width (RDW), mean corpuscular volume (MCV), erythrocyte volume fraction (EVF)), leukocyte count (total count, lymphocytes, neutrophils) and thrombocyte count in 5312 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS). The associations between increasing copeptin tertile and the hematopoietic markers were analyzed in multivariate linear regression analyses. We found that increasing copeptin tertile was significantly (p < 0.001) associated with increasing erythrocytes, RDW, EVF, Hb, leukocytes and neutrophils after adjustment for age, sex, current smoking, prevalent diabetes, hypertension, creatinine, body mass index and physical activity. Increasing copeptin tertile was, however, not associated with change in MCV, lymphocyte or thrombocyte count. In conclusion, we found that increasing copeptin levels are positively associated with markers of erythropoiesis and leukocyte count in the general population. These results warrant further research on possible mechanistic effects of vasopressin on hematopoiesis.
Background This study aims to describe associations of obesity and CKD in a Swedish urban population. The impact of fat mass, from bioimpedance analysis, on eGFR based on cystatin C and/or creatinine ...is studied. Methods 5049 participants from Malmö Diet and Cancer Study the cardiovascular arm (MDCS-CV) with available body mass composition (single frequency bioimpedance analysis) and cystatin C measured at baseline were selected. Body mass index (kg/m.sup.2) was used to define overweight/obesity. eGFR was calculated using cystatin C (eGFR.sub.CYS) and creatinine (eGFR.sub.CR) equations: Chronic Kidney Disease Epidemiology Collaboration 2012 (CKD-EPI.sub.CR, CKD-EPI.sub.CYS, CKD-EPI.sub.CR-CYS).sub., eGFR.sub.CYS based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised equation (LMrev), and Modified Full Age Spectrum creatinine-based equation (EKFC.sub.CR). Two different fat mass index (FMI) z-scores were calculated: FMI z-score.sub.Larsson and FMI z-score.sub.Lee. Results Lower eGFR.sub.CYS and eGFR.sub.CR-CYS following multiple adjustments were prevalent in overweight/obese subjects. Increase in FMI z-score.sub.Larsson or FMI z-score.sub.Lee was related to decrease in predicted CAPA, CKD-EPI.sub.CYS, CKD-EPI.sub.CR-CYS and CAPA-LMrev equation. Conclusion eGFR.sub.CYS, in contrast to combined eGFR.sub.CR-CYS and eGFR.sub.CR, demonstrate the strongest association between FMI and kidney function.
Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in ...middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults.
We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness.
Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001).
Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.
Abstract Introduction Red cell distribution width (RDW) has been associated with venous thromboembolism (VTE), but whether RDW is a predictor of first event of VTE is unknown. We investigated the ...association between RDW and incidence of first event of VTE in a population-based cohort. Materials and Methods RDW was measured in 27 042 subjects (aged 45–73 years, 60.6% women), without previous history of VTE or cancer within 5 years before follow-up, who participated in the Malmö Diet and Cancer study during 1991–1996. Incidence of VTE was identified from the patient register and the cause of death register during a mean follow-up of 13.8 years and studied in relation to RDW. Results During follow-up, 991 subjects (57.5% women) were affected by VTE (pulmonary embolism or deep venous thrombosis of the lower limbs). After adjustment for potential confounding factors the hazard ratios (HR) for VTE for the second, third and fourth RDW quartiles 1.15 (95% confidence interval 0.94–1.41), 1.41 (1.14–1.73), 1.74 (1.38–2.21), respectively, were compared with the bottom quartile of RDW. In the multivariate model subjects with the top 5% of RDW values compared with the bottom quartile had an even higher risk (HR = 2.51, 1.78–2.54). In receiver operating characteristic (ROC) analysis, the male specific area under the ROC curve (AUC) for RDW was 0.57 (95% CI 0.54–0.59). The female specific AUC was 0.56 (95% CI 0.53–0.58). Conclusions RDW was found to be associated with long-term incidence of first event of VTE among middle-aged subjects.
Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the ...largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly (
<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 95% CI, 0.41-0.85), whereas early vascular aging had higher risk (hazard ratio, 2.70 95% CI, 1.55-4.70) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.
Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a ...challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers.
The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression.
Median B-Cd was 0.22 μg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per μg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 μg/L; OR 1.21; 95 % confidence interval 1.01-1.45).
Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.