Individuals at high risk for chronic cardiometabolic disease (cardiovascular disease [CVD], type 2 diabetes, and chronic kidney disease [CKD]) share many risk factors and would benefit from early intervention. We developed a nonlaboratory-based risk-assessment tool for identification of people at high cardiometabolic disease risk.
RESEARCH DESIGN AND METHODS
Data of three population-based cohorts from different regions of the Netherlands were merged. Participants were 2,840 men and 3,940 women, white, aged 28–85 years, free from CVD, type 2 diabetes, and CKD diagnosis at baseline. The outcome was developing cardiometabolic disease during 7 years follow-up.
Age, BMI, waist circumference, antihypertensive treatment, smoking, family history of myocardial infarction or stroke, and family history of diabetes were significant predictors, whereas former smoking, history of gestational diabetes, and use of lipid-lowering medication were not. The models showed acceptable calibration (Hosmer and Lemeshow statistics, P > 0.05) and discrimination (area under the receiver operating characteristic [ROC] curve 0.82 [95% CI 0.81–0.83] for women and 0.80 [0.78–0.82] for men). Discrimination of individual outcomes was lowest for diabetes (area under the ROC curve 0.70 for men and 0.73 for women) and highest for CVD mortality (0.83 for men and 0.85 for women).
We demonstrate that a single risk stratification tool can identify people at high risk for future CVD, type 2 diabetes, and/or CKD. The present risk-assessment tool can be used for referring the highest risk individuals to health care for further (multivariable) risk assessment and may as such serve as an important part of prevention programs targeting chronic cardiometabolic disease.
The prognostic impact of reduced glomerular filtration rate (GFR) in chronic heart failure (CHF) is increasingly recognised, but little is known about tubular damage in these patients.
To investigate the prevalence of tubular damage, and its association with GFR, and prognosis in patients with CHF.
Methods and results
In 90 patients with CHF, GFR and effective renal plasma flow (ERPF) were measured ([125I] iothalamate and [131I]hippuran clearances). The tubular markers neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as well as urinary albumin excretion were determined in 24 h urine collections. Mean GFR was 78±26 ml/min/1.73 m2. Urinary NGAL (175 (70—346) mg/g creatinine (gCr)), NAG (12 (6—17) U/gCr) and KIM-1 (277 (188—537) ng/gCr) levels were increased compared with 20 healthy controls (all p<0.001). Urinary NAG, but not NGAL or KIM-1 correlated with GFR (r=−0.34, p=0.001) and ERPF (r=−0.29, p=0.006). Both NAG (r=0.21, p=0.048) and KIM-1 (r=0.23, p=0.033) correlated with plasma N-terminal pro-brain natriuretic peptide levels. Both urinary KIM-1 (HR=1.15 (95% CI 1.02 to 1.30) per 100 ng/gCr increase, p=0.025) and NAG (HR=1.42 (95% CI 1.02 to 1.94) per 5 U/gCr increase, p=0.039), were associated with an increased risk of death or heart failure hospitalisations, independent of GFR.
Tubular damage, as indicated by increased urinary concentrations of NGAL, NAG and KIM-1 is common in patients with CHF and mildly reduced GFR. Both urinary KIM-1 and NAG showed prognostic information additional to GFR. These findings suggest an important role for tubular damage and tubular markers in cardiorenal interaction in heart failure.
Oxidative stress has been suggested to play a key role in the development of cardiovascular disease (CVD). The aim of our study was to investigate the associations of serum peroxiredoxin 4 (Prx4), a hydrogen peroxide–degrading peroxidase, with incident CVD and all-cause mortality. We subsequently examined the incremental value of Prx4 for the risk prediction of CVD compared with the Framingham risk score (FRS).
Methods and Results
We performed Cox regression analyses in 8141 participants without history of CVD (aged 28 to 75 years; women 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, The Netherlands. Serum Prx4 was measured by an immunoluminometric assay in baseline samples. Main outcomes were: (1) incident CVD events or CVD mortality and (2) all-cause mortality during a median follow-up of 10.5 years. In total, 708 participants (7.8%) developed CVD events or CVD mortality, and 517 participants (6.3%) died. Baseline serum Prx4 levels were significantly higher in participants with incident CVD events or CVD mortality and in those who died than in participants who remained free of outcomes (both P<0.001). In multivariable models with adjustment for Framingham risk factors, hazard ratios were 1.16 (95% CI 1.06 to 1.27, P<0.001) for incident CVD events or CVD mortality and 1.17 (95% CI 1.06 to 1.29, P=0.003) for all-cause mortality per doubling of Prx4 levels. After the addition of Prx4 to the FRS, the net reclassification improvement was 2.7% (P=0.01) using 10-year risk categories of CVD.
Elevated serum Prx4 levels are associated with a significantly higher risk of incident CVD events or CVD mortality and all-cause mortality after adjustment for clinical risk factors. The addition of Prx4 to the FRS marginally improved risk prediction of future CVD.
cardiovascular disease; epidemiology; mortality; oxidative stress; peroxiredoxin 4
The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome.
Cardiorenal syndrome; Heart-kidney interaction; Animal models
Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI.
We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI.
In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 μg/L, and 4.16 μg/L, respectively, and decreased more gradually.
Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.
Copeptin; Acute myocardial infarction; Biomarkers; Temporal release pattern; Troponin
The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure–associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1–7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways.
Heart failure; Renin; Prorenin; Cardiorenal
Renal function is the most important predictor of clinical outcome in heart failure (HF). It is therefore essential to have accurate and reliable measurement of renal function and early specific markers of renal impairment in patients with HF. Several renal functional entities exist, including glomerular filtration (GFR), glomerular permeability, tubulointerstitial damage, and endocrine function. Different markers have been studied that can be used to determine changes and the effect of treatment in these entities. In the present review, we summarize current and novel markers that give an assessment of renal function and prognosis in the setting of acute and chronic HF.
Renal function; Heart failure; Glomerular filtration rate; gfr; Albuminuria; Tubular damage; Cystatin C; N-acetyl-beta-d-glucosaminidase; Kidney injury molecule 1; Neutrophil gelatinase-associated lipocalin; FABP; Interleukin 18; IL-18; mdrd; NAG; KIM-1; NGAL
Background. We used a random sample (n = 2, 495) from the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study population to examine the association of the metabolic syndrome (Met S) with plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) antigen levels. Results. The overall prevalence of the Met S was 18%, was dependent on age and gender, and was positively associated with higher antigen levels of both PAI-1 and t-PA. These significant effects were maintained after adjustment for age, gender, BMI, elevated C-reactive protein, smoking status, urinary albumin excretion, and insulin levels. We found no significant interactions between the Met S and other covariates on PAI-1 and t-PA levels. Conclusions. Our study demonstrates that those with the Met S have significantly higher levels of PAI-1 and t-PA antigen, factors known to increase the risk of cardiovascular disease.
Galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (lvef), and compared this to other biomarkers.
We studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization.
A doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62–2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07–1.78; P = 0.015). Galectin-3 levels were correlated with higher il-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (RoC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001).
Galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.
Biomarkers; galectin-3; heart failure; prognosis; remodeling
Vascular fibrinolytic balance is maintained primarily by interplay of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous research has shown that polymorphisms in genes from the renin-angiotensin (RA), bradykinin, and fibrinolytic systems affect plasma concentrations of both t-PA and PAI-1 through a set of gene-gene interactions. In the present study, we extend this finding by exploring the effects of polymorphisms in genes from these systems on incident cardiovascular disease, explicitly examining two-way interactions in a large population-based study.
Data from the population-based PREVEND study in Groningen, The Netherlands (n = 8,138) were analyzed. The effects of the polymorphisms and their interactions on cardiovascular events were analyzed via Cox proportional hazards models. There was no association between five of the six polymorphisms singly and risk of cardiovascular disease. There was a significant main effect for the ACE I/D polymorphism for both dominant and additive coding schemes. There were significant interactions between the following polymorphism pairs even after adjustment for known risk factors: ACE I/D & PAI-1 4G/5G (p = 0.012), BDKRB2 C181T & ACE I/D (p = 0.016), BDKRB2 C58T & ACE I/D (p = 0.025), BDKRB2 exon 1 I/D & AT1R A1166C (p = 0.017), and BDKRB2 C58T & AT1R A1166C (p = 0.015).
This study suggests possible interactions between genes from the RA, bradykinin, and fibrinolytic systems on the risk of cardiovascular disease, extending previous research that has demonstrated that interactions among genes from these systems influence plasma concentrations of both t-PA and PAI-1. Further explorations of these interactions are needed.
Biomarkers are increasingly being used in the management of patients with chronic heart failure (HF). Galectin-3 is a recently developed biomarker associated with fibrosis and inflammation, and it may play a role in cardiac remodeling in HF. We determined its prognostic value in patients with chronic HF.
Methods and results
Patients with chronic HF (New York Heart Association functional class III or IV) who participated in the Deventer–Alkmaar heart failure study were studied. Galectin-3 levels were determined at baseline using a novel optimized enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine the prognostic value of this biomarker. We studied 232 patients; their mean age was 71 ± 10 years, 72% were male, and 96% were in NYHA class III. During a follow-up period of 6.5 years, 98 patients died. Galectin-3 was a significant predictor of mortality risk after adjustment for age and sex, and severity of HF and renal dysfunction, as assessed by NT-proBNP and estimated glomerular filtration rate, respectively (hazard ratio per standard deviation 1.24, 95% CI 1.03–1.50, P = 0.026).
Plasma galectin-3 is a novel prognostic marker in patients with chronic HF. Its prognostic value is independent of severity of HF, as assessed by NT-proBNP levels, and it may potentially be used in the management of such patients.
Galectin-3; Chronic heart failure; Biomarkers; Prognosis
Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF.
Methods and results
Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64–79) years, 61% male, left ventricular ejection fraction of 30 (23–44)%, and the estimated glomerular filtration rate was 53 (40–68) ml/min/1.73 m2. Telomere length was associated with renal function (correlation coefficient 0.123, P < 0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings.
The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure.
Telomere; Renal function; Heart failure
We determined the efficiency of a screening protocol based on coronary calcium scores (CCS) compared with exercise testing in patients with suspected coronary artery disease (CAD), a normal ECG and troponin levels. Three-hundred-and-four patients were enrolled in a screening protocol including CCS by electron beam computed tomography (Agatston score), and exercise testing. Decision-making was based on CCS. When CCS≥400, coronary angiography (CAG) was recommended. When CCS<10, patients were discharged. Exercise tests were graded as positive, negative or nondiagnostic. The combined endpoint was defined as coronary event or obstructive CAD at CAG. During 12±4 months, CCS≥400, 10–399 and <10 were found in 42, 103 and 159 patients and the combined endpoint occurred in 24 (57%), 14 (14%) and 0 patients (0%), respectively. In 22 patients (7%), myocardial perfusion scintigraphy was performed instead of exercise testing due to the inability to perform an exercise test. A positive, nondiagnostic and negative exercise test result was found in 37, 76 and 191 patients, and the combined endpoint occurred in 11 (30%), 15 (20%) and 12 patients (6%), respectively. Receiver-operator characteristics analysis showed that the area under the curve of 0.89 (95% CI: 0.85–0.93) for CCS was superior to 0.69 (95% CI: 0.61–0.78) for exercise testing (P<0.0001). In conclusion, measurement of CCS is an appropriate initial screening test in a well-defined low-risk population with suspected CAD.
Coronary calcium; Exercise test; MDCT; EBCT; Coronary artery disease
Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II type 1 receptor (AT1R). In addition, bradykinin can induce the release of t-PA through a B2 receptor mechanism. In the present study, we aimed to investigate the epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin and fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based sample (n=2,527). We demonstrated a strong significant interaction within genetic variations of the bradykinin B2 gene (p=0.002) and between ACE and bradykinin B2 (p=0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels (p=0.006). In both females as well as males, the bradykinin B2 gene interacted with AT1R gene on plasma PAI-1 levels (p=0.026 and p=0.039, respectively). In addition, the current study found a borderline significant interaction between PAI 4G5G and ACE I/D on plasma t-PA and PAI-1 levels. These results support the idea that the interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems might play an important role in t-PA and PAI-1 biology.
Plasminogen; thrombosis; gene-gene interaction; epistasis; epidemiology; fibrinolysis
We present an extension of the two-class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of a quantitative trait. The proposed Quantitative MDR (QMDR) method handles continuous data by modifying MDR’s constructive induction algorithm to use a T-test. QMDR replaces the balanced accuracy metric with a T-test statistic as the score to determine the best interaction model. We used a simulation to identify the empirical distribution of QMDR’s testing score. We then applied QMDR to genetic data from the ongoing prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.
Clinical Decision Support Systems (CDSSs) can support guideline adherence in heart failure (HF) patients. However, the use of CDSSs is limited and barriers in working with CDSSs have been described as a major obstacle. It is unknown if barriers to CDSSs are present and differ between HF nurses and cardiologists. Therefore the aims of this study are; 1. Explore the type and number of perceived barriers of HF nurses and cardiologists to use a CDSS in the treatment of HF patients. 2. Explore possible differences in perceived barriers between two groups. 3. Assess the relevance and influence of knowledge management (KM) on Responsibility/Trust (R&T) and Barriers/Threats (B&T).
A questionnaire was developed including; B&T, R&T, and KM. For analyses, descriptive techniques, 2-tailed Pearson correlation tests, and multiple regression analyses were performed.
The response- rate of 220 questionnaires was 74%. Barriers were found for cardiologists and HF nurses in all the constructs. Sixty-five percent did not want to be dependent on a CDSS. Nevertheless thirty-six percent of HF nurses and 50% of cardiologists stated that a CDSS can optimize HF medication. No relationship between constructs and age; gender; years of work experience; general computer experience and email/internet were observed. In the group of HF nurses a positive correlation (r .33, P<.01) between years of using the internet and R&T was found. In both groups KM was associated with the constructs B&T (B=.55, P=<.01) and R&T (B=.50, P=<.01).
Both cardiologists and HF-nurses perceived barriers in working with a CDSS in all of the examined constructs. KM has a strong positive correlation with perceived barriers, indicating that increasing knowledge about CDSSs can decrease their barriers.
Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.
The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).
MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.
ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.
Cardiorenal failure; Atherosclerotic renal artery stenosis; Magnetic resonance imaging; Late gadolinium enhancement
Although the value of telemonitoring in heart failure patients is increasingly studied, little is known about the value of the separate components of telehealth: ICT guided disease management and telemonitoring. The aim of this study is to investigate the value of telemonitoring added to ICT guided disease management (DM) on the quality and efficiency of care in patients with chronic heart failure (CHF) after a hospitalisation.
The study is divided in two arms; a control arm (DM) and an intervention arm (DM+TM) in 10 hospitals in the Netherlands. In total 220 patients will be included after worsening of CHF (DM: N = 90, DM+TM: N = 130). Total follow-up will be 9 months. Data will be collected at inclusion and then after 2 weeks, 4.5 and 9 months. The primary endpoint of this study is a composite score of: 1: death from any cause during the follow-up of the study, 2: first readmission for HF and 3: change in quality of life compared to baseline, assessed by the Minnesota Living with Heart failure Questionnaire. The study has started in December 2009 and results are expected in 2012.
The IN TOUCH study is the first to investigate the effect of telemonitoring on top of ICT guided DM on the quality and efficiency of care in patients with worsening HF and will use a composite score as its primary endpoint.
Netherlands Trial Register (NTR): NTR1898
Asymptomatic subjects at intermediate coronary risk may need diagnostic testing for risk stratification. Both measurement of coronary calcium scores and exercise testing are well established tests for this purpose. However, it is not clear which test should be preferred as initial diagnostic test. We evaluated the prevalence of documented coronary artery disease (CAD) according to calcium scores and exercise test results.
Asymptomatic subjects with ST-T changes on a rest ECG were selected from the population based PREVEND cohort study and underwent measurement of calcium scores by electron beam tomography and exercise testing. With calcium scores ≥10 or a positive exercise test, myocardial perfusion imaging (MPS) or coronary angiography (CAG) was recommended. The primary endpoint was documented obstructive CAD (≥50% stenosis).
Of 153 subjects included, 149 subjects completed the study protocol. Calcium scores ≥400, 100–399, 10–99 and <10 were found in 16, 29, 18 and 86 subjects and the primary endpoint was present in 11 (69%), 12 (41%), 0 (0%) and 1 (1%) subjects, respectively. A positive, nondiagnostic and negative exercise test was present in 33, 27 and 89 subjects and the primary endpoint was present in 13 (39%), 5 (19%) and 6 (7%) subjects, respectively. Receiver operator characteristics analysis showed that the area under the curve, as measure of diagnostic yield, of 0.91 (95% CI 0.84–0.97) for calcium scores was superior to 0.74 (95% CI 0.64–0.83) for exercise testing (p = 0.004).
Measurement of coronary calcium scores is an appropriate initial non-invasive test in asymptomatic subjects at increased coronary risk.