Prevalence of coronary artery calcification in a non-specific chest pain population in emergency and cardiology departments compared with the background population: a prospective cohort study in Southern Denmark with 12-month follow-up of cardiac endpoints.

OBJECTIVES: To examine and compare the prevalence of coronary artery calcification (CAC) and the frequency of cardiac events in a background population and a cohort of patients with non-specific chest pain (NSCP) who present to an emergency or cardiology department and are discharged without an obvious reason for their symptom. DESIGN: A double-blinded, prospective, observational cohort study that measures both CT-determined CAC scores and cardiac events after 1 year of follow-up. SETTING: Emergency and cardiology departments in the Region of Southern Denmark. SUBJECTS: In total, 229 patients with NSCP were compared with 722 patients from a background comparator population. MAIN OUTCOMES MEASURES: Prevalence of CAC and incidence of unstable angina (UAP), acute myocardial infarction (MI), ventricular tachycardia (VT), coronary revascularisation and cardiac-related mortality 1 year after index contact. RESULTS: There was no significant difference in the prevalence of CAC (OR 0.9 (95% CI 0.6 to 1.3), P=0.546) or the frequency of cardiac endpoints (P=0.64) between the studied groups. When compared with the background population, the OR for patients with NSCP for a CAC >100 Agatston units (AU) was 1.0 (95% CI 0.6 to 1.5), P=0.826. During 1 year of follow-up, two (0.9%) patients with NSCP underwent cardiac revascularisation, while none experienced UAP, MI, VT or death. In the background population, four (0.6%) participants experienced a clinical cardiac endpoint; two had an MI, one had VT and one had a cardiac-related death. CONCLUSION: The prevalence of CAC (CAC >0 AU) among patients with NSCP is comparable to a background population and there is a low risk of a cardiac event in the first year after discharge. A CAC study does not provide notable clinical utility for risk-stratifying patients with NSCP. TRIAL REGISTRATION NUMBER: NCT02422316; Pre-results.

Prognostic value of suPAR and hs-CRP on cardiovascular disease.

BACKGROUND AND AIMS: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. METHODS: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models. RESULTS: 1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01-1.34) and 1.04 (95% CI 1.01-1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45-2.84) and 60-year-old subjects (1.44; 95% CI 1.09-1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32). CONCLUSIONS: Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.

CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers.

OBJECTIVES: This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. BACKGROUND: CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. METHODS: At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. RESULTS: A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). CONCLUSIONS: In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.

Associations between calcium-phosphate metabolism and coronary artery calcification; a cross sectional study of a middle-aged general population.

BACKGROUND AND AIMS: High serum calcium-phosphate levels are associated with increased risk of cardiovascular disease (CVD) in patients with chronic kidney disease. Recent studies have demonstrated this relationship also in subjects with normal kidney function. Our aim was to examine whether calcium-phosphate metabolism is associated with the presence and extent of coronary artery calcification (CAC) in asymptomatic and apparently healthy individuals. METHODS: Serum samples from 1088 randomly recruited middle-aged men and women without known CVD and diabetes (DM), from the general population, were analysed for total calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D). CAC was measured by a non-contrast cardiac CT scan and categorised into four groups: 0, 1-99, 100-399, ≥400 Agatston units. The association of calcium-phosphate metabolism with CAC was evaluated by a multiple ordered logistic regression model. All the multiple regression analyses were performed in the entire cohort as well as in men and women separately. RESULTS: In the study population, 96% of the serum calcium values, 93% of the PTH values, 90% of the phosphate values, and only 64% of the 25(OH)D values were placed within the normal range. In men, the odds of being in a higher CAC category, i.e. having more severe CAC, increased by 30% when serum calcium concentration increased by 0.1 mmol/l (95% CI: 1.04-1.61, p = 0.019), independently of traditional cardiovascular risk factors. In women, no significant association between serum calcium and CAC was identified (OR 0.99, 95% CI: 0.81-1.21, p = 0.91). Neither phosphate, PTH nor 25(OH)D was significantly associated with CAC in men, in women or when performed in the entire cohort. CONCLUSIONS: Serum calcium, even with values within normal range and independent of traditional risk factors, was significantly associated with CAC in asymptomatic and apparently healthy middle-aged men, but not in women.