Impact of Smoking on Coronary Volume-to-Myocardial Mass Ratio: An ADVANCE Registry Substudy.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm3 ± 934.0 [SD]; never-smokers, 2967.6 mm3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm3/g ± 7.9; former smokers, 24.9 mm3/g ± 7.1; never-smokers, 25.8 mm3/g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article. © RSNA, 2024.

Coronary computed tomography angiography derived fractional flow reserve and risk of recurrent angina: A 3-year follow-up study.

BACKGROUND: The association between coronary computed tomography angiography (CTA) derived fractional flow reserve (FFRCT) and risk of recurrent angina in patients with new onset stable angina pectoris (SAP) and stenosis by CTA is uncertain. METHODS: Multicenter 3-year follow-up study of patients presenting with symptoms suggestive of new onset SAP who underwent first-line CTA evaluation and subsequent standard-of-care treatment. All patients had at least one ≥30 â€‹% coronary stenosis. A per-patient lowest FFRCT-value ≤0.80 represented an abnormal test result. Patients with FFRCT ≤0.80 who underwent revascularization were categorized according to completeness of revascularization: 1) Completely revascularized (CR-FFRCT), all vessels with FFRCT ≤0.80 revascularized; or 2) incompletely revascularized (IR-FFRCT) ≥1 vessels with FFRCT ≤0.80 non-revascularized. Recurrent angina was evaluated using the Seattle Angina Questionnaire. RESULTS: Amongst 769 patients (619 [80 â€‹%] stenosis ≥50 â€‹%, 510 [66 â€‹%] FFRCT ≤0.80), 174 (23 â€‹%) reported recurrent angina at follow-up. An FFRCT ≤0.80 vs â€‹> â€‹0.80 associated to increased risk of recurrent angina, relative risk (RR): 1.82; 95 â€‹% CI: 1.31-2.52, p â€‹< â€‹0.001. Risk of recurrent angina in CR-FFRCT (n â€‹= â€‹135) was similar to patients with FFRCT >0.80, 13 â€‹% vs 15 â€‹%, RR: 0.93; 95 â€‹% CI: 0.62-1.40, p â€‹= â€‹0.72, while IR-FFRCT (n â€‹= â€‹90) and non-revascularized patients with FFRCT ≤0.80 (n â€‹= â€‹285) had increased risk, 37 â€‹% vs 15 â€‹% RR: 2.50; 95 â€‹% CI: 1.68-3.73, p â€‹< â€‹0.001 and 30 â€‹% vs 15 â€‹%, RR: 2.03; 95 â€‹% CI: 1.44-2.87, p â€‹< â€‹0.001, respectively. Use of antianginal medication was similar across study groups. CONCLUSION: In patients with SAP and coronary stenosis by CTA undergoing standard-of-care guided treatment, FFRCT provides information regarding risk of recurrent angina.

Coronary Volume to Left Ventricular Mass Ratio in Patients With Hypertension.

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm3 vs 2,965.6 ± 943.7 mm3, p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm3/g vs 25.3 ± 7.3 mm3/g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm3, p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm3/g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension.

Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults.

Importance: Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk. Objective: To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum. Design, Setting, and Participants: This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021. Exposures: Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden. Main Outcomes and Measures: Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death. Results: A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque. Conclusions and Relevance: The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

Coronary CT angiography-derived fractional flow reserve in-stable angina: association with recurrent chest pain.

AIMS: The aim of this study was to evaluate the association between coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) and recurrent chest pain (CP) at 1-year follow-up in patients with stable angina pectoris (SAP). METHODS AND RESULTS: Study of patients (n = 267) with SAP who underwent CCTA and FFRCT testing; 236 (88%) underwent invasive coronary angiography; and 87 (33%) were revascularized. Symptomatic status at 1-year follow-up was gathered by a structured interview. Three different FFRCT algorithms were applied using the following criteria for abnormality: (i) 2 cm-FFRCT ≤0.80; (ii) d-FFRCT ≤0.80; and (iii) a combination in which both a d-FFRCT ≤0.80 and a ΔFFRCT ≥0.06 must be present in the same vessel (c-FFRCT). Patients were classified into two groups based on the FFRCT test result and revascularization: completely revascularized/normal (CRN), patients in whom all coronary arteries with an abnormal FFRCT test result were revascularized or patients with completely normal FFRCT test results, and incompletely revascularized (IR), patients in whom ≥1 coronary artery with an abnormal FFRCT test result was not revascularized. Recurrent CP was present in 62 (23%) patients. Classification of patients (CRN or IR) was significantly associated with recurrent CP for all applied FFRCT interpretation algorithms. When applying the c-FFRCT algorithm, the association with recurrent CP was found, irrespective of the extent of coronary calcification and the degree of coronary stenosis. A negative association between per-patient minimal d-FFRCT and recurrent CP was demonstrated, P < 0.005. CONCLUSION: An abnormal FFRCT test result is associated with an increased risk of recurrent CP in patients with new-onset SAP.

Extent of arterial calcification by conventional vitamin K antagonist treatment.

BACKGROUND AND AIMS: Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). METHODS: We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates. RESULTS: The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category. CONCLUSIONS: Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.

Coronary flow impairment in asymptomatic patients with early stage type-2 diabetes: Detection by FFRCT.

PURPOSE: To determine the occurrence of physiological significant coronary artery disease (CAD) by coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) in asymptomatic patients with a new diagnosis (<1 year) of type-2 diabetes mellitus (T2DM). METHODS: FFRCT-analysis was performed from standard acquired coronary CTA data sets. The per-patient minimum distal FFRCT-value (d-FFRCT) in coronary vessels (diameter ⩾1.8 mm) was registered. The threshold for categorizing FFRCT-analysis as abnormal was a d-FFRCT ⩽0.75. Total plaque volume and volumes of calcified plaque, non-calcified plaque, and low-density non-calcified plaque (LD-NCP) were assessed by quantitative plaque analysis. RESULTS: Overall, 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49(65), were studied. A total of 57% of patients had plaques. The d-FFRCT was ⩽0.75 in 12 (16%) patients. The d-FFRCT, median (IQR), was 0.84 (0.79-0.87). Median (range) d-FFRCT in patients with d-FFRCT ⩽0.75 was 0.70 (0.6-0.74). Patients with d-FFRCT⩽0.75 versus d-FFRCT >0.75 had numerically higher plaque volumes for all plaques components, although only significant for the LD-NCP component. CONCLUSION: Every sixth asymptomatic patient with a new diagnosis of T2DM has hemodynamic significant CAD as evaluated by FFRCT. Flow impairment by FFRCT was associated with coronary plaque characteristics.

1-Year Impact on Medical Practice and Clinical Outcomes of FFRCT: The ADVANCE Registry.

OBJECTIVES: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. BACKGROUND: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. METHODS: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. RESULTS: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFRCT ≤0.80 and 12 occurred in those with an FFRCT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). CONCLUSIONS: The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679).

Pressure Recovery in the Left Main Stenosis.

A 76-year-old male patient with dyspnea was referred on a suspicion of coronary artery disease. A coronary computed tomography angiography (CTA) revealed a distal left main (LM) stenosis and in the right (right coronary artery [RCA]), left circumflex (LCX) and left anterior descending (LAD) coronary arteries stenosis could not be excluded. CTA-derived fractional flow reserve (FFRct) was 0.75, 0.72, 0.74, 0.86, and 0.94 in the LM, LAD, LCX, ramus, and RCA, respectively. Invasive coronary angiography confirmed a stenosis in the LM and LAD. FFR was 0.73 and 0.85 in the LCX and ramus, respectively. The patient was referred for coronary artery bypass surgery. The FFR and FFRct values in the ramus demonstrate the phenomenon of pressure recovery. This case shows that preserved FFR and FFRct cannot always be used to exclude the hemodynamic significance of upstream coronary lesions.

Prospective Comparison of FFR Derived From Coronary CT Angiography With SPECT Perfusion Imaging in Stable Coronary Artery Disease: The ReASSESS Study.

OBJECTIVES: This study sought to compare the per-patient diagnostic performance of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) with that of single-photon emission computed tomography (SPECT), using a fractional flow reserve (FFR) value of ≤0.80 as the reference for diagnosing at least 1 hemodynamically significant stenosis in a head-to-head comparison of patients with intermediate coronary stenosis as determined by coronary CTA. BACKGROUND: No previous study has prospectively compared the diagnostic performance of FFRCT and myocardial perfusion imaging by SPECT in symptomatic patients with intermediate range coronary artery disease (CAD). METHODS: This study was conducted at a single-center as a prospective study in patients with stable angina pectoris (N = 143). FFRCT and SPECT analyses were performed by core laboratories and were blinded for the personnel responsible for downstream patient management. FFRCT ≤0.80 distally in at least 1 coronary artery with a diameter ≥2 mm classified patients as having ischemia. Ischemia by SPECT was encountered if a reversible perfusion defect (summed difference score ≥2) or transitory ischemic dilation of the left ventricle (ratio >1.19) were found. RESULTS: The per-patient diagnostic performance for identifying ischemia (95% confidence interval [CI]), FFRCT versus SPECT, were sensitivity of 91% (95% CI: 81% to 97%) versus 41% (95% CI: 29% to 55%; p < 0.001); specificity of 55% (95% CI: 44% to 66%) versus 86% (95% CI: 77% to 93%; p < 0.001); negative predictive value of 90% (95% CI: 82% to 98%) versus 68% (95% CI: 59% to 77%; p = 0.001); positive predictive value of 58% (95% CI: 48% to 68%) versus 67% (95% CI: 51% to 82%; p = NS); and accuracy of 70% (95% CI: 62% to 77%) versus 68% (95% CI: 60% to 75%; p = NS) respectively. CONCLUSIONS: In patients with stable chest pain and CAD as determined by coronary CTA, the overall diagnostic accuracy levels of FFRCT and SPECT were identical in assessing hemodynamically significant stenosis. However, FFRCT demonstrated a significantly higher diagnostic sensitivity than SPECT.

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.

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.

Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects.

OBJECTIVE: The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac computed tomography (CT) scan. DESIGN: A cross sectional study of 1126 randomly sampled middle-aged men and women. METHODS: CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI). RESULTS: The odds of being in a higher CAC category, i.e. having more severe CAC, increased 16% (odds ratio (OR) 1.16, p = 0.02) when plasma suPAR concentration increased 1 ng/ml, and this was more pronounced in women (OR 1.30, p = 0.01) than in men (OR 1.15, p = 0.05). In comparison, hs-CRP was not associated with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 (p = 0.04) in women and from 0.65 to 0.68 (p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1-32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0-40.7, p = 0.04), without significant gender difference. CONCLUSIONS: suPAR, but not hs-CRP, appeared to be associated with CAC score independently of SCORE. The association was strongest in women.

Can osteoprotegerin be used to identify the presence and severity of coronary artery disease in different clinical settings?

PURPOSE: The biomarker Osteoprotegerin (OPG) is associated with coronary artery disease (CAD). The main purpose of this study was to evaluate the diagnostic value of OPG in healthy subjects and in patients with suspected angina pectoris (AP). METHODS: A total of 1805 persons were enrolled: 1152 healthy subjects and 493 patients with suspected AP. For comparison 160 patients with acute myocardial infarction (MI) were included. To uncover subclinical coronary atherosclerosis, a non-contrast cardiac-CT scan was performed in healthy subjects; while in patients with suspected AP a contrast coronary angiography was used to detect significant stenosis. OPG concentrations were analyzed and compared between groups. ROC-analyses were performed to estimate OPG cut-off values. RESULTS: OPG concentrations increased according to disease severity with the highest levels found in patients with acute MI. No significant difference (p = 0.97) in OPG concentrations was observed between subgroups of healthy subjects according to severity of coronary calcifications. A significant difference (p < 0.0001) in OPG concentrations was found between subgroups of patients with suspected stable AP according to severity of CAD. ROC-analysis showed an AUC of 0.62 (95% CI: 0.57-0.67). The optimal cut-off value of OPG (<2.29 ng/mL) had a sensitivity of 56.2% (95% CI: 49.2-63.0%) and a specificity of 62.9% (95% CI: 57.3-68.2%). CONCLUSION: OPG cannot be used to differentiate between healthy subjects with low versus high levels of coronary calcifications. In patients with suspected AP a single OPG measurement is of limited use in the diagnosis of CAD.

Coronary artery calcification and ECG pattern of left ventricular hypertrophy or strain identify different healthy individuals at risk.

PURPOSE: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification. METHOD: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A noncontrast computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage × QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association between the presence of CAC, clinical variables and ECG findings was evaluated by means of multivariate logistic regression. RESULTS: Of 1825 invited individuals, 1226 accepted the screening. The prevalence of hypertension was 50%. Hypertensive patients frequently had LVH and/or strain when compared with nonhypertensive individuals (21 vs. 14%, P < 0.0001) as well as CAC (52 vs. 38%, P < 0.0001). In multiple logistic regressions analyses, there was no association between the ECG abnormalities and the presence of CAC. CONCLUSION: There appears to be no relationship between CAC and ECG-suspected LVH and/or strain. We propose that these markers identify different individuals at risk and together may have additive prognostic value.

Population screening for coronary artery calcification does not increase mental distress and the use of psychoactive medication.

PURPOSE: Detection of coronary artery calcification (CAC) has been proposed for population screening. It remains unknown whether such a strategy would result in unnecessary concern among participants. Therefore, we set out to assess whether CAC screening affects the psychological well-being of screening participants. MATERIALS AND METHODS: A random sample of 1825 middle-aged subjects (men and women, 50 or 60 y old) were invited for health screening. The European HeartScore was calculated, and a CAC score was measured using a cardiac computed tomography scanner. Therapeutic interventions as a result of the observations were at the discretion of the individual general practitioner. Before screening and at 6-month follow-up a depression test (Major Depression Inventory) was conducted, and the use of psychoactive medication was recorded. RESULTS: A total of 1257 (69%) subjects agreed to participate. Because of known cardiovascular disease or diabetes mellitus, 88 persons were excluded. Of the remaining 1169, 47% were men, and one half were 50 years old. At 6-month follow-up, significant reductions were observed in the Major Depression Inventory score from 5.3 to 3.9 (P<0.0001) and in the prescription rates of psychoactive medication from 7.1% (83 of 1169) to 6.2% (72 of 1169) (P=0.003). The results were independent of sex, age, HeartScore, CAC Score, and changes in other medication. CONCLUSIONS: A population screening program including CAC score appears to have no detrimental impact on mental distress and does not increase the use of psychoactive medication.

Changes in medical treatment six months after risk stratification with HeartScore and coronary artery calcification scanning of healthy middle-aged subjects.

OBJECTIVES: The aim was to examine and compare the impact of HeartScore and coronary artery calcification (CAC) score on subsequent changes in the use of medication. METHODS: A total of 1156 healthy men and women, aged 50 or 60, had a baseline medical examination and a coronary artery CT-scan as a part of a screening programme. Using the European HeartScore, the total 10-year cardiovascular mortality risk was estimated (≥5% risk was considered as high). Risk factors and CAC scores were reported to both the patients and their general practitioner. Six months after the screening, follow-up questionnaires addressing current medication were mailed to the participants. RESULTS: A completed questionnaire was returned by 1075 (93%) subjects. At follow up, the overall use of prophylactic medication was significantly increased. Of those with CAC (n = 462) or high HeartScore (n = 233), 21 and 19%, respectively, received lipid-lowering treatment, while 25 and 32%, respectively, received antihypertensive treatment. In multivariate logistic regression analyses, the presence of CAC was associated with an increased use of lipid-lowering treatment (OR 2.2; 95% CI 1.2-4.0), while the presence of a high HeartScore was associated with an increased use of lipid-lowering (OR 2.9; 95% CI 1.6-5.5) and antihypertensive medication (OR 3.4; 95% CI 1.9-6.0). CONCLUSION: Knowledge of present cardiovascular risk factors like high HeartScore and/or CAC leads to beneficial changes in medication. However, at follow up only a minority of high-risk subjects did received prophylactic treatment. CAC score was not superior to HeartScore regarding these motivational outcomes.