Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD.

OBJECTIVES: The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD. BACKGROUND: Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse. METHODS: Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries. RESULTS: The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment. CONCLUSIONS: The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

Risk stratification by assessment of coronary artery disease using coronary computed tomography angiography in diabetes and non-diabetes patients: a study from the Western Denmark Cardiac Computed Tomography Registry.

AIMS: We examined whether severity of coronary artery disease (CAD) measured by coronary computed tomography angiography can be used to predict rates of myocardial infarction (MI) and death in patients with and without diabetes. METHODS AND RESULTS: A cohort study of consecutive patients (n = 48 731) registered in the Western Denmark Cardiac Computed Tomography Registry from 2008 to 2016. Patients were stratified by diabetes status and CAD severity (no, non-obstructive, or obstructive). Endpoints were MI and death. Event rates per 1000 person-years, unadjusted and adjusted incidence rate ratios were computed. Median follow-up was 3.6 years. Among non-diabetes patients, MI event rates per 1000 person-years were 1.4 for no CAD, 4.1 for non-obstructive CAD, and 9.1 for obstructive CAD. Among diabetes patients, the corresponding rates were 2.1 for no CAD, 4.8 for non-obstructive CAD, and 12.6 for obstructive CAD. Non-diabetes and diabetes patients without CAD had similar low rates of MI [adjusted incidence rate ratio 1.40, 95% confidence interval (CI): 0.71-2.78]. Among diabetes patients, the adjusted risk of MI increased with severity of CAD (no CAD: reference; non-obstructive CAD: adjusted incidence rate ratio 1.71, 95% CI: 0.79-3.68; obstructive CAD: adjusted incidence rate ratio 4.42, 95% CI: 2.14-9.17). Diabetes patients had higher death rates than non-diabetes patients, irrespective of CAD severity. CONCLUSION: In patients without CAD, diabetes patients have a low risk of MI similar to non-diabetes patients. Further, MI rates increase with CAD severity in both diabetes and non-diabetes patients; with diabetes patients with obstructive CAD having the highest risk of MI.

Myocardial Perfusion Imaging Versus Computed Tomography Angiography-Derived Fractional Flow Reserve Testing in Stable Patients With Intermediate-Range Coronary Lesions: Influence on Downstream Diagnostic Workflows and Invasive Angiography Findings.

BACKGROUND: Data on the clinical utility of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) are sparse. In patients with intermediate (40-70%) coronary stenosis determined by coronary computed tomography angiography, we investigated the association of replacing standard myocardial perfusion imaging with FFRCT testing with downstream utilization of invasive coronary angiography (ICA) and the diagnostic yield of ICA (rate of no obstructive disease, and rate of revascularization). METHODS AND RESULTS: This was a single-center observational study of symptomatic patients with suspected coronary artery disease referred to coronary computed tomography angiography between 2013 and 2015. Patients were divided into 3 historical groups based on the adjunctive functional testing approach: myocardial perfusion imaging (n=1332) or FFRCT "implementation" (n=800) or "clinical use" (n=1391). Propensity score matching was used to estimate the average period effect on outcomes. Patients in the FFRCT clinical use group versus the myocardial perfusion imaging group were older and had higher pretest probability of obstructive disease. After adjusting for baseline risk characteristics, there was a reduction in downstream ICA utilization (absolute risk difference: -4.2; 95% CI, -6.9 to -1.6; P=0.002). In patients referred to ICA, findings of no obstructive coronary artery disease decreased (-12.8%; 95% CI, -22.2 to -3.4; P=0.008) and rate of coronary revascularization increased (14.1%; 95% CI, 3.3-24.9; P=0.01), as did availability of functional information for guidance of revascularization (27.8%; 95% CI, 11.3-44.4; P<0.001) after clinical adoption of FFRCT. CONCLUSIONS: Replacing adjunctive myocardial perfusion imaging with FFRCT testing for functional assessment of intermediate stenosis determined by coronary computed tomography angiography in stable coronary artery disease was associated with less ICA utilization, and a higher ICA diagnostic yield. The findings in this observational study needs confirmation in prospective, randomized trials.

Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study.

Aims: To examine the 3.5 year prognosis of stable coronary artery disease (CAD) as assessed by coronary computed tomography angiography (CCTA) in real-world clinical practice, overall and within subgroups of patients according to age, sex, and comorbidity. Methods and results: This cohort study included 16,949 patients (median age 57 years; 57% women) with new-onset symptoms suggestive of CAD, who underwent CCTA between January 2008 and December 2012. The endpoint was a composite of late coronary revascularization procedure >90 days after CCTA, myocardial infarction, and all-cause death. The Kaplan-Meier estimator was used to compute 91 day to 3.5 year risk according to the CAD severity. Comparisons between patients with and without CAD were based on Cox-regression adjusted for age, sex, comorbidity, cardiovascular risk factors, concomitant cardiac medications, and post-CCTA treatment within 90 days. The composite endpoint occurred in 486 patients. Risk of the composite endpoint was 1.5% for patients without CAD, 6.8% for obstructive CAD, and 15% for three-vessel/left main disease. Compared with patients without CAD, higher relative risk of the composite endpoint was observed for non-obstructive CAD [hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01-1.63], obstructive one-vessel CAD (HR: 1.83; 95% CI: 1.37-2.44), two-vessel CAD (HR: 2.97; 95% CI: 2.09-4.22), and three-vessel/left main CAD (HR: 4.41; 95% CI :2.90-6.69). The results were consistent in strata of age, sex, and comorbidity. Conclusion: Coronary artery disease determined by CCTA in real-world practice predicts the 3.5 year composite risk of late revascularization, myocardial infarction, and all-cause death across different groups of age, sex, or comorbidity burden.

Visualization of Coronary Artery Calcification: Influence on Risk Modification.

OBJECTIVES: Direct health provider to patient presentation of coronary computed tomography angiography findings may increase adherence to preventive therapy and risk modification. The purpose of this study was to assess the influence of visualization of coronary artery calcification and lifestyle recommendations on cholesterol concentrations and other risk variables in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia. METHODS: We performed a prospective 2-center randomized controlled trial. Patients were randomized 1:1 to intervention or standard follow-up in general practice. The primary end point was change in plasma total cholesterol concentration at 6 months follow-up. RESULTS: We included 189 patients (mean [± standard deviation] age 61 [12] years, 57% were male). Median (range) Agatston score was 166 (70-2054). The reduction in plasma total cholesterol concentrations tended to be higher in the intervention group than in the control group, 51.04 mg/dL versus 45.63 mg/dL (P = .181). In a subgroup including patients continuing statin therapy during follow-up (n = 147), the reduction in plasma total cholesterol concentrations was more pronounced in the intervention group than in the control group, 66.13 mg/dL versus 55.68 mg/dL (P = .027). In the intervention group, there was a higher degree of statin adherence and a higher proportion of patients who stopped smoking and commenced healthier dietary behavior than in the control group. CONCLUSIONS: Visualization of coronary artery calcification and brief recommendations about risk modification after coronary computed tomography angiography in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia may have a favorable influence on plasma total cholesterol concentration, adherence to statin therapy, and risk behavior. Further investigations are needed.

The diagnostic accuracy and outcomes after coronary computed tomography angiography vs. conventional functional testing in patients with stable angina pectoris: a systematic review and meta-analysis.

AIMS: To systematically review and perform a meta-analysis of the diagnostic accuracy and post-test outcomes of conventional exercise electrocardiography (XECG) and single-photon emission computed tomography (SPECT) compared with coronary computed tomography angiography (coronary CTA) in patients suspected of stable coronary artery disease (CAD). METHODS AND RESULTS: We systematically searched for studies published from January 2002 to February 2013 examining the diagnostic accuracy (defined as at least ≥50% luminal obstruction on invasive coronary angiography) and outcomes of coronary CTA (≥16 slice) in comparison with XECG and SPECT. The search revealed 11 eligible studies (N = 1575) comparing the diagnostic accuracy and 7 studies (N = 216.603) the outcomes of coronary CTA vs. XECG or/and SPECT. The per-patient sensitivity [95% confidence interval (95% CI)] to identify significant CAD was 98% (93-99%) for coronary CTA vs. 67% (54-78%) (P < 0.001) for XECG and 99% (96-100%) vs. 73% (59-83%) (P = 0.001) for SPECT. The specificity (95% CI) of coronary CTA was 82% (63-93%) vs. 46% (30-64%) (P < 0.001) for XECG and 71% (60-80%) vs. 48% (31-64%) (P = 0.14) for SPECT. The odds ratio (OR) of downstream test utilization (DTU) for coronary CTA vs. XECG/SPECT was 1.38 (1.33-1.43, P < 0.001), for revascularization 2.63 (2.50-2.77, P < 0.001), for non-fatal myocardial infarction 0.53 (0.39-0.72, P < 0.001), and for all-cause mortality 1.01 (0.87-1.18, P = 0.87). CONCLUSION: The up-front diagnostic performance of coronary CTA is higher than of XECG and SPECT. When compared with XECG/SPECT testing, coronary CTA testing is associated with increased DTU and coronary revascularization.

Effects on costs of frontline diagnostic evaluation in patients suspected of angina: coronary computed tomography angiography vs. conventional ischaemia testing.

AIMS: The aim of this study was to investigate in patients with stable angina the effects on costs of frontline diagnostics by exercise-stress testing (ex-test) vs. coronary computed tomography angiography (CTA). METHODS AND RESULTS: In two coronary units at Lillebaelt Hospital, Denmark, 498 patients were identified in whom either ex-test (n = 247) or CTA (n = 251) were applied as the frontline diagnostic strategy in symptomatic patients with a low-intermediate pre-test probability of coronary artery disease (CAD). During 12 months of follow-up, death, myocardial infarction and costs associated with downstream diagnostic utilization (DTU), treatment, ambulatory visits, and hospitalizations were registered. There was no difference between cohorts in demographic characteristics or the pre-test probability of significant CAD. The mean (SD) age was 56 (11) years; 52% were men; and 96% were at low-intermediate pre-test probability of CAD. All serious cardiac events (n = 3) during follow-up occurred in patients with a negative ex-test result. Mean costs per patient associated with DTU, ambulatory visits, and cardiovascular medication were significantly higher in the ex-test than in the CTA group. The mean (SD) total costs per patient at the end of the follow-up were 14% lower in the CTA group than in the ex-test group, € 1510 (3474) vs. €1777 (3746) (P = 0.03). CONCLUSION: Diagnostic assessment of symptomatic patients with a low-intermediate probability of CAD by CTA incurred lower costs when compared with the ex-test. These findings need confirmation in future prospective trials.

Association of ischemic stroke to coronary artery disease using computed tomography coronary angiography.

BACKGROUND: While patients with coronary artery disease (CAD) and cerebrovascular disease share similar risk factor profiles, data on whether IS can be considered a "CAD equivalent" are limited. We aimed to determine whether ischemic stroke is an independent predictor of CAD by using cardiac computed tomography angiography (CTA). METHODS: We analyzed the CTA in 392 patients with no history of CAD (24 patients with acute IS and 368 patients with acute chest pain). Extent of plaque burden was additionally dichotomized into 0-4 versus >4 segments. RESULTS: Patients with IS had a near 5-fold increase odds of having coronary artery plaque (odds ratio [OR] 4.9, P<0.01) as compared to those without IS. After adjustment for age, gender, and traditional cardiac risk factors, there remained a near 4-fold increase odds for coronary plaque (adjusted OR 3.7, P=0.04). When stratified by extent of plaque, patients with IS had over 18-fold increase odds of having >4 segments of plaque than 0-4 segments as compared to patients without stroke (OR 18.3, P<0.01), which remained significantly associated in adjusted analysis (adjusted OR 12.1, P<0.001). CONCLUSION: Acute IS is independently associated with higher risk and greater extent of CAD compared to patients with acute chest pain at low-to-intermediate risk for acute coronary syndrome.

Frontline diagnostic evaluation of patients suspected of angina by coronary computed tomography reduces downstream resource utilization when compared to conventional ischemia testing.

It has been proposed that the increasing use of coronary computed tomographic angiography (CTA) may introduce additional unnecessary diagnostic procedures. However, no previous study has assessed the impact on downstream test utilization of conventional diagnostic testing relative to CTA in patients suspected of angina. The purpose of this study was to investigate the consequences of frontline exercise-stress testing (Ex-test) versus CTA on downstream test utilization in clinical practice. In two collaborating departments using either Ex-test (n = 247) or CTA (n = 251) as the frontline diagnostic test in patients suspected of angina, comparable cohorts of consecutive patients were retrospectively identified (Jan. 2007-Feb. 2008). Downstream test utilization (invasive coronary angiography, ICA; myocardial perfusion scintigraphy, and CTA) during 12 months after the index diagnostic test was recorded. Mean age was 56 years (51% men), and 96% of the total study cohort were at low-intermediate pretest risk of significant coronary disease. Overall, downstream test utilization was more frequent in the Ex-test group than in the CTA group, 32% versus 21% (P = 0.003). Subsequent myocardial scintigraphy was more frequent used (9% versus 4%, P = 0.03), whereas ICA tended to be more frequent applied in the Ex-test versus CTA group (23% vs. 18%, P = 0.15). A frontline diagnostic use in symptomatic patients of Ex-test in comparison to CTA leads to more downstream diagnostic test utilization. Future prospective trials are needed in order to define the most cost-effective diagnostic use of CTA relative to conventional ischemia testing.

Paradigm of pretest risk stratification before coronary computed tomography.

BACKGROUND: The optimal method of determining the pretest risk of coronary artery disease as a patient selection tool before coronary multidetector computed tomography (MDCT) is unknown. OBJECTIVE: We investigated the ability of 3 different clinical risk scores to predict the outcome of coronary MDCT. METHODS: This was a retrospective study of 551 patients consecutively referred for coronary MDCT on a suspicion of coronary artery disease. Diamond-Forrester, Duke, and Morise risk models were used to predict coronary artery stenosis (>50%) as assessed by coronary MDCT. The models were compared by receiver operating characteristic analysis. The distribution of low-, intermediate-, and high-risk persons, respectively, was established and compared for each of the 3 risk models. RESULTS: Overall, all risk prediction models performed equally well. However, the Duke risk model classified the low-risk patients more correctly than did the other models (P < 0.01). In patients without coronary artery calcification (CAC), the predictive value of the Duke risk model was superior to the other risk models (P < 0.05). Currently available risk prediction models seem to perform better in patients without CAC. Between the risk prediction models, there was a significant discrepancy in the distribution of patients at low, intermediate, or high risk (P < 0.01). CONCLUSIONS: The 3 risk prediction models perform equally well, although the Duke risk score may have advantages in subsets of patients. The choice of risk prediction model affects the referral pattern to MDCT.

Selection at work in self-incompatible Arabidopsis lyrata: mating patterns in a natural population.

Identification and characterization of the self-incompatibility genes in Brassicaceae species now allow typing of self-incompatibility haplotypes in natural populations. In this study we sampled and mapped all 88 individuals in a small population of Arabidopsis lyrata from Iceland. The self-incompatibility haplotypes at the SRK gene were typed for all the plants and some of their progeny and used to investigate the realized mating patterns in the population. The observed frequencies of haplotypes were found to change considerably from the parent generation to the offspring generation around their deterministic equilibria as determined from the known dominance relations among haplotypes. We provide direct evidence that the incompatibility system discriminates against matings among adjacent individuals. Multiple paternity is very common, causing mate availability among progeny of a single mother to be much larger than expected for single paternity.