Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease.

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28-4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59-0.72). Calibration for models II-V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59-29.39)) and model V (NRI 20.00% (95%CI 5.59-34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

Multifocal cardiovascular calcification in patients with established cardiovascular disease; prevalence, risk factors, and relation with recurrent cardiovascular disease.

AIMS: The aim is to investigate (multifocal) cardiovascular calcification in patients with established cardiovascular disease (CVD), regarding prevalence, risk factors, and relation with recurrent CVD or vascular interventions. Coronary artery calcification (CAC), thoracic aortic calcification (TAC) (including ascending aorta, aortic arch, descending aorta), mitral annular calcification (MAC), and aortic valve calcification (AVC) are studied. METHODS: The study concerned 568 patients with established CVD enrolled in the ORACLE cohort. All patients underwent computed tomography. Prevalence of site-specific and multifocal calcification was determined. Ordinal regression analyses were performed to quantify associations of risk factors with cardiovascular calcification, and Cox regression analyses to determine the relation between calcium scores and recurrent CVD or vascular interventions. RESULTS: Calcification was multifocal in 76% (N = 380) of patients with calcification. Age (per SD) was associated with calcification at all locations (lowest OR 2.17; 99%CI 1.54-3.11 for ascending aorta calcification). Diabetes mellitus and systolic blood pressure were associated with TAC, whereas male sex was a determinant of CAC. TAC and CAC were related to the combined endpoint CVD or vascular intervention (N = 68). In a model with all calcium scores combined, only CAC was related to the combined outcome (HR 1.39; 95%CI 1.15-1.68). CONCLUSION: Cardiovascular calcification is generally multifocal in patients with established CVD. Differences in associations between risk factors and calcification at various anatomical locations stress the divergence in pathophysiological pathways. CAC is most strongly related to recurrent CVD or vascular interventions independent of traditional risk factors, and independent of heart valve and thoracic aorta calcification.

Prediction of Lifetime and 10-Year Risk of Cancer in Individual Patients With Established Cardiovascular Disease.

BACKGROUND: Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer. OBJECTIVES: The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD. METHODS: Data from patients with established CVD from the UCC-SMART cohort (N = 7,280) were used for model development, and from the CANTOS trial (N = 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer. RESULTS: Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer. CONCLUSIONS: Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening.

The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.

AIMS: Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. METHODS AND RESULTS: In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). CONCLUSION: Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.