Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease.
Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation.
A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991-1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded.
After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p
Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on incidence of cardiovascular events among middle-aged nondiabetic subjects.
Department of Clinical Sciences, Internal Medicine Research Group, University Hospital Malmö, Entrance 33, level 2, SE-205 02 Malmö, Sweden. margaretha.m.persson@skane.se
BACKGROUND: To explore potential interrelationships between lipoprotein-associated phospholipase A2 (Lp-PLA2), the metabolic syndrome (MetS), and incident cardiovascular disease (CVD). METHODS AND RESULTS: MetS was defined by the National Cholesterol Education Program Adult treatment Panel III criteria in 4480 nondiabetic Malmö Diet and Cancer Study subjects without history of CVD. Incidence of first CVD event (stroke [130 cases] or myocardial infarction [131]) was monitored over 10 years of follow-up. Lp-PLA2 activity and mass were significantly higher in subjects with MetS. Lp-PLA2 activity compared with Lp-PLA2 mass was more strongly correlated to individual components and increased more linearly with number of MetS components. Elevated Lp-PLA2 activity (top compared with bottom tertile), but not elevated Lp-PLA2 mass, increased risk for incident CVD (relative risk, RR: 1.54, 95% CI 1.07 to 2.24), as did MetS (1.42, 1.06 to 1.90) after taking possible confounders into account. Relative to those without either elevated Lp-PLA2 activity or MetS, combination of MetS and elevated Lp-PLA2 activity increased risk for CVD (1.97, 1.34 to 2.90). Elevated Lp-PLA2 activity without MetS increased risk for CVD (1.40, 1.03 to 1.92) but not MetS without elevated Lp-PLA2 activity (1.46, 0.94 to 2.27). CONCLUSION: Lp-PLA2 is associated to the MetS. Higher plasma levels of Lp-PLA2 increased risk for incident CVD regardless of MetS. The simultaneous presence of elevated Lp-PLA2 activity and MetS may identify an especially high risk individual.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme that is produced by inflammatory cells (macrophages, T-lymphocytes and mast cells) and hydrolyzes oxidized phospholipids in LDL. Several epidemiology studies indicate that Lp-PLA(2) appears to be an independent marker of cardiovascular risk. This study was conducted to define the distribution of Lp-PLA(2) in a large population-based cohort and to determine associations between Lp-PLA(2) and other risk factors for CVD. The study group consisted of participants from the Malm? Diet and Cancer study (1992-1994). Lp-PLA(2) (activity and mass) was measured from samples obtained at baseline for 5402 participants (3167 women). A strong correlation was observed between Lp-PLA(2) activity and mass in this study (r=0.57). Highest correlations were observed between Lp-PLA(2) activity and LDL (r=0.45) and LDL/HDL ratio (r=0.54) and a strong inverse correlation to HDL (r=-0.31). The correlations between Lp-PLA(2) mass and lipids were not as strong as the correlation between activity and lipids. Lp-PLA(2) activity and mass were correlated with increased ultrasound determined carotid intima-media thickness. We conclude that Lp-PLA(2) is strongly correlated with several cardiovascular risk factors, especially lipid fractions, and with the degree of carotid artery atherosclerosis. However, the measured variables accounted for only 19% and 35% of the variation in Lp-PLA(2) mass and activity respectively.
Lipoprotein-associated phospholipase A2 concentrations in plasma are associated with the extent of coronary artery disease and correlate to adipose tissue levels of marine n-3 fatty acids.
Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Arhus University Hospitals, Sdr. Skovvej 15, 9100 Aalborg, Denmark. ebs@dadlnet.dk
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor for cardiovascular disease. In the present study, plasma levels of Lp-PLA(2) were measured in patients (n=301) admitted to elective coronary angiography because of suspected coronary artery disease (CAD). In a multiple linear regression analysis, the degree of CAD (0-, 1-, 2- or 3-vessel disease) and plasma LDL cholesterol significantly correlated to Lp-PLA(2) levels. Also the content of the marine n-3 fatty acid, eicosapentaenoic acid (EPA) in adipose tissue, a measure of long-term intake of seafood independently and inversely (r=-0.18, p
Cardiovascular Research Laboratories, Cardiology Division, Royal Victoria Hospital, McGill University/McGill University Health Centre, Montreal, Québec, Canada; Programme de Sciences Biomédicales, Faculté de Médecine, Université de Montréal, Montreal, Québec, Canada.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) might play a role in the formation of vulnerable atherosclerotic plaques. Its plasma distribution and mass in subjects with acute coronary syndrome (ACS) has yet to be characterized.
We compared plasma levels of Lp-PLA2 in 24 patients within 48 hours of an ACS (acute) and 12 weeks after (recovery), in 26 patients with stable coronary artery disease and in 10 normal healthy control subjects. Lp-PLA2 mass was determined using enzyme-linked immunosorbent assay.
The ACS patients (mean age 57 ? 8.7 years) had high-sensitivity C-reactive protein (hsCRP) levels of 30.46 ? 57.57 mg/L (ACS acute) vs 1.69 ? 1.32 mg/L (ACS recovery). Plasma Lp-PLA2 levels were significantly higher in ACS acute subjects than in ACS recovery subjects (143.13 ? 60.88 ng/mL vs 88.74 ? 39.12 ng/mL; P 65%-70% of Lp-PLA2 mass was within the apolipoprotein B-containing lipoprotein fraction, with approximately 30%-35% on HDL fraction, with no significant change in distribution between ACS acute and recovery.
Subjects with an ACS have markedly increased Lp-PLA2 levels acutely related to LDL-C levels.
BACKGROUND: Data regarding the association between lipoprotein-associated phospholipase A2 (Lp-PLA(2)) level and incidence of cardiovascular (CV) events are conflicting. This prospective urban population-based study explored the relationship between baseline Lp-PLA(2) activity and mass, respectively, levels and incidence of first coronary heart disease (CHD) and ischemic stroke, respectively. METHODS: Lp-PLA(2) activity and mass were assessed in 5393 (60% women) subjects who participated in the Malmö Diet and Cancer Study cardiovascular program during 1991-1994. RESULTS: In all 347 subjects had an event (195 CHD and 152 ischemic strokes) during the follow-up period (mean 10.6+/-1.7 years). In an age-, sex- and CV risk factors-adjusted Cox regression analysis, comparing top to bottom tertile of Lp-PLA(2) activity, the relative risk [RR; 95% confidence interval (CI)] for incident CHD and ischemic stroke events were 1.48; 0.92-2.37 and RR: 1.94; 1.15-3.26, respectively. The corresponding figures for Lp-PLA(2) mass were 0.95; 0.65-1.40 and RR: 1.92; 1.20-3.10. CONCLUSION: Elevated levels of Lp-PLA(2) activity and mass, respectively, were in this study, independently of established risk factors related to the incidence of ischemic stroke but after adjustment for lipids not significant related to incident CHD.
