Suspected Stable Angina Pectoris Research Articles

B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study

BackgroundCalcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. ObjectiveWe explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12, and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. MethodsPatient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications. ResultsA total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]). ConclusionsIn patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.

Physical activity and risk of all-cause mortality in patients with stable angina pectoris: Effect modification by β-blocker treatment

BackgroundPhysical activity (PA) influences sympathetic stimulation, platelet activation as well as vascular function, and has been associated with improved health outcomes in patients with coronary heart disease. β-blocker therapy reduces sympathetic activity and improves platelet and endothelial function. We investigated if β-blocker treatment modifies the association of self-reported PA with the risk of all-cause mortality. MethodsA total of 2284 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) were studied. Using Cox modeling, we examined associations between PA (categorized as ‘sedentary/inactive’, ‘low’, ‘moderate’, and ‘high’) and all-cause mortality according to β-blocker therapy. ResultsDuring a median follow-up of 10.3 years, 390 patients (17.1%) died. Higher PA was generally associated with a more favorable cardiovascular risk profile. Compared to the patients who were sedentary or inactive, the age and sex adjusted HRs (95% CI) for all-cause mortality were 0.89 (0.66–1.20), 0.73 (0.57–0.95) and 0.72 (0.55–0.95) in the low, moderate and high PA group, respectively. However, and notably, these risk estimates were 0.85 (0.60–1.20), 0.65 (0.47–0.89) and 0.58 (0.41–0.81) in β-blocker treated subjects vs. 1.00 (0.57–1.78), 0.96 (0.61–1.52) and 1.20 (0.74–1.95) in non-treated groups (Pinteraction = 0.018). The results were essentially similar in the multivariable adjusted models. ConclusionsIn patients with suspected SAP, increased PA was associated with reduced mortality risk primarily in patients treated with β-blockers.

Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris.

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08-1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12-1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10-1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00-1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00-1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/e' and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/e' and Duke Score.

HDL, apo a1 and long-term cardio-metabolic prognosis in statin-treated patients with suspected stable angina pectoris: a prospective cohort study

Abstract Background Reduced serum levels of high density lipoprotein cholesterol (HDL-C) is a hallmark of the metabolic syndrome. Epidemiologic studies have reported an inverse correlation between HDL- C and cardiovascular disease (CVD) risk. However, recent works suggest that the association is strongest in healthy individuals. Changes in particle number and functional properties of HDL may more closely reflect CVD prognosis in patients with pre-existent disease. The majority of such patients receive statin treatment, which affects both HDL-C levels, and particle composition. Hence, serum apoA1 and the HDL-C:apoA1 ratio have been proposed as more sensitive indicators of cardio-metabolic prognosis. Purpose We studied the associations of serum HDL-C, apoA1 and the HDL-C: apoA1 ratio to long term risk of CVD mortality and incident type 2 diabetes (T2D) patients with suspected stable angina pectoris (SAP). Methods A total of 41064 patients underwent elective coronary angiography in 2000–2004 and were followed-up for CVD mortality throughout 2016. In a subgroup of 2519 participants without verified or possible diabetes at baseline, the associations to incident type 2 diabetes (T2D) were evaluated throughout 2014. Information on clinical endpoints was obtained through national health registries. Risk estimates are reported per 1 SD increment of (log transformed) biomarkers and were calculated by cox or logistic regression. We explored risk classification by calculating the continuous net reclassification improvement (NRI). Results At inclusion, median (25th-75th percentiles) age was 62 (55–70) years, 28% were women 76% had obstructive coronary artery disease and 80% received statins. During median (25th-75th percentiles) 13.9 (12.0–15.3) years of follow-up, 14.1% of the participants died from CVD. After multivariate adjustment (age, gender, body mass index, HbA1c, triglycerides, statin treatment, fasting status) HDL and apoA1, but not the HDL: apoA1 ratio, significantly predicted CVD mortality. The hazard ratio (HR) and 95% confidence interval (CI) was: 0.86 (0.78–0.94), 0.88 (0.80–0.98) and 0.96 (0.86–1.03) for HDL-C, apoA1 and the HDL-C:apoA1 ratio, respectively. HDL-C was the only of the evaluated biomarkers providing a significant NRI (95% CI) of 0.14 (0.04–0.19). In the subset evaluated for incdent T2D, HDL-C provided multivariate adjusted odds ratios (OR; 95% CI) and NRI (95% CI) of 0.69 (0.58–0.82) and 0.34 (0.21–0.47) for new onset TSD. The corresponding OR (95% CI) and NRI (95% CI) for apoA1 were: 0.85 (0.73–0.99) and 0.20 (0.06–0.33), respectively. The HDL:apo A1 ratio provided an OR (95% CI) of 0.66 (0.55–0.80) and NRI (95% CI) of 0.24 (0.11–0.37) for T2D. No significant effect modifications according to statin treatment were found (P≥0.22). Conclusion Among patients with suspected SAP, of which the majority received statins, HDL-C was non-inferior to apoA1 and the HDL:apoA1 ratio in predicting long term risk of CVD mortality and T2D. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Heart Disease, Haukeland University Hospital; Department of Clinical Science, University of Bergen

Early diastolic strain rate by two-dimensional speckle tracking echocardiography is a predictor of coronary artery disease and cardiovascular events in stable angina pectoris.

This study aimed to clarify the diagnostic and prognostic potential of strain rate in patients with suspected stable angina pectoris (SAP). Strain rate by 2-dimensional speckle tracking echocardiography (2DSTE) has been suggested to be able to diagnose coronary artery disease (CAD) and predict cardiovascular events in various patient groups. Prospectively enrolled patients (n = 296) with suspected SAP, no previous cardiac disease, and normal left ventricular ejection fraction were examined by 2DSTE, exercise ECG, and coronary angiography. Obstructive CAD was defined as stenosis ≥ 70% in ≥ 1 coronary artery on coronary angiography (n = 107). Major adverse cardiac events (MACE) included myocardial infarction, heart failure, atrial fibrillation, and stroke. In multivariable analysis adjusted for baseline data, conventional echocardiography, and Duke score, early diastolic strain rate (SRe) was independently associated with significant CAD with a 1.35 increased risk of having CAD per 0.1 decrease in SRe (OR = 1.35, 95% CI 1.03-1.76, P = 0.027). Peak velocity of early diastolic filling (E)/SRe was not associated with significant CAD (OR = 1.14, 95% CI 0.81-1.62, P = 0.445). MACE occurred in 34 patients (12%) during follow-up (median 3.5years) and both SRe (HR 1.26, 95% CI (1.07-1.49), P = 0.006) and E/SRe (HR 1.24, 95% CI (1.04-1.47), P = 0.017) were independent predictors after multivariable adjustment. In patients with suspected SAP, SRe by 2DSTE was independently associated with presence of CAD. In addition, SRe and E/SRe provided independent and incremental prognostic value for predicting future MACE.

Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin

ObjectivesOxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ–mediated immune...

Postsystolic shortening on echocardiography as a gateway to cardiac computed tomography in patients with suspected stable angina pectoris.

Postsystolic shortening (PSS) by speckle-tracking echocardiography (STE) is a marker of myocardial ischemia and may improve diagnostic strategy. We sought to evaluate if PSS is associated with the coronary artery calcium score (CACS) and stenosis by computed tomography angiography (CTA) in patients with suspected stable angina pectoris (SAP). We retrospectively studied 437 SAP patients (age 58 ± 11years, 41% male) who underwent STE, evaluation of CACS and assessment of significant stenosis (≥ 50%) by CTA. The postsystolic index (PSI) was defined as follows: 100x([peak negative strain cardiac cycle - peak negative strain systole])/peak negative strain cardiac cycle. A wall had PSS if any segment within the wall had a PSI ≥ 20%. We defined categories for walls with PSS: 0, 1, 2 and ≥ 3, and CACS: 0, 1-100, 101-400 and > 400. Each additional wall with PSS was associated with a 43% relative increase in CACS (95%CI +9% to +87%, P = 0.010), while each 1% absolute increase in the PSI was associated with a 9% relative increase in CACS (95%CI +1% to +18%, P = 0.031). Walls with PSS (OR 1.81 per 1 wall increase, 95%CI 1.27-2.59, P = 0.001) and the PSI (OR 1.12 per 1% increase, 95%CI 1.04-1.21, P = 0.004) were associated withthe occurrence of CACS > 400. Additionally, walls with PSS (OR 1.53 per 1 wall increase, 95%CI 1.21-1.93, P < 0.001) was a predictor of significant stenosis by CTA. PSS is associated with CACS and significant stenosis by CTA in patients with SAP and may aid in the selection of patients referred for cardiac computed tomography.

Dietary choline is related to increased risk of acute myocardial infarction in patients with stable angina pectoris

High plasma choline has been associated with the metabolic syndrome and risk of chronic diseases, including cardiovascular disease. However, dietary choline is not correlated with choline plasma concentrations, and there are few studies and contradictory evidence regarding dietary choline and cardiovascular events. In addition, a recommended dietary allowance for choline has not been established and remains a point of contention.This study assessed the association between dietary choline, including choline forms, and risk of incident acute myocardial infarction (AMI) in patients with suspected stable angina pectoris (SAP).In total 1981 patients (80% men, median age 62) from the Western Norway B Vitamin Intervention Trial were included in this analysis. Information on dietary choline was obtained using a 169-item food frequency questionnaire. The Cardiovascular Disease in Norway project provided data on AMI. Risk associations were estimated using Cox-regression analysis using energy-adjusted choline intake.Median (25th, 75th percentile) total energy-adjusted choline intake was 288 (255, 326) mg/d. During a median (25th, 75th percentile) follow-up of 7.5 (6.3, 8.8) years, 312 (15.7%) patients experienced at least one AMI. Increased intakes of energy-adjusted choline (HR [95% CI] per 50 mg increase 1.11 [1.03, 1.20]), phosphatidylcholine (HR per 50 mg increase 1.24 [1.08, 1.42]) and sphingomyelin (HR per 5 mg increase 1.16 [1.02, 1.31]) were associated with higher AMI risk.In conclusion, higher dietary intakes of total choline, phosphatidylcholine and sphingomyelin were associated with increased risk of AMI in patients with SAP. Future studies are necessary to explore underlying mechanisms for this observation.

Usefulness of layer-specific strain in diagnosis of coronary artery disease in patients with stable angina pectoris.

Novel software allows for layer-specific evaluation of myocardial strain by speckle tracking echocardiography (2DSTE). However, the potential of layer-specific strain at rest for diagnosing coronary artery disease (CAD) in patients with suspected stable angina pectoris (SAP) remains unknown. Our objective wasto evaluate the usefulness of layer-specific 2DSTE at rest for diagnosis of CAD in patients with SAP. In total, 285 patients referred with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were prospectively enrolled. All patients were examined by echocardiography, including 2DSTE, exercise ECG, and coronary angiography (CAG). Layer-specific 2DSTE was performed in three apical views to provide longitudinal peak systolic strains. Stenosis ≥ 70% in ≥ 1 major coronary artery on CAG was considered as significant CAD. Of 285 patients included, 104 had significant CAD (36%). Endocardial, epicardial, and mid-myocardial GLS were all significantly impaired in CAD patients (P < 0.001). Multivariable analysis including baseline clinical parameters, conventional echocardiographic measurements, Duke score, and layer-specific strain measurements revealed epicardial [odds ratio 1.19 (P = 0.048)] and mid-myocardial [odds ratio 1.16 (P = 0.047)] global longitudinal strain (GLS) as the only independent predictors of CAD. In direct comparison, epicardial and mid-myocardial GLS had a significantly higher diagnostic performance compared to endocardial GLS (P = 0.038 and P = 0.031, respectively). In conclusion, layer-specific GLS from 2DSTE at rest was significantly impaired in patients with significant CAD. In addition, epicardial and mid-myocardial GLS were independent predictors of CAD.

Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease

Elevated circulating cystathionine levels are related to atherosclerotic cardiovascular disease, a leading cause of death globally. We investigated whether plasma cystathionine was associated with mortality in patients with suspected or established coronary heart disease (CHD). Data from 2 independent cohorts of patients with suspected stable angina pectoris (SAP) (3033 patients; median 10.7 y follow-up; 648 deaths) or acute myocardial infarction (AMI) (3670 patients; median 7.0 y follow-up; 758 deaths) were included. Hazard ratios with 95% CIs per SD increment of log-transformed cystathionine were calculated using Cox regression modeling. Endpoint data was obtained from a national health registry. Among patients with SAP, there was a positive association between plasma cystathionine and death (age- and sex-adjusted HRs [95% CI] per SD: 1.23 [1.14, 1.32], 1.29 [1.16, 1.44], and 1.17 [1.05, 1.29] for total, cardiovascular, and noncardiovascular mortality, respectively). Corresponding risk estimates were 1.28 (1.19, 1.37) for all-cause, 1.33 (1.22, 1.45) for cardiovascular, and 1.19 (1.06, 1.34) for noncardiovascular death among AMI patients. In both cohorts, estimates were slightly attenuated after multivariate adjustments for established CHD risk factors. Subgroup analyses showed that the relation between cystathionine and all-cause mortality in SAP patients was stronger among nonsmokers and those with lower plasma concentration of pyridoxal-5'-phosphate (P-interaction≤0.01 for both). Elevated plasma cystathionine is associated with both cardiovascular and noncardiovascular mortality among patients with suspected or established CHD. The joint risk associations of high plasma cystathionine with lifestyle factors and impaired vitamin B-6 status on mortality need further investigation. This trial was registered at clinicaltrials.gov as NCT00354081 and NCT00266487.

Usefulness of Postsystolic Shortening to Diagnose Coronary Artery Disease and Predict Future Cardiovascular Events in Stable Angina Pectoris

Postsystolic shortening (PSS) may occur during myocardial ischemia. We aimed to assess the diagnostic and prognostic potential of PSS in patients with suspected stable angina pectoris (SAP). This is a prospective study of patients with suspected SAP (N=293), no prior cardiac history, and normal ejection fraction, who were examined by speckle-tracking echocardiography, coronary angiography, and exercise electrocardiogram. We excluded patients with known heart disease (ischemia, heart failure, valve disease), bundle branch block, pathological Q-waves, and arrhythmias. PSS was assessed using the postsystolic index (PSI), and categorical presence of PSS was defined as PSI≥20% in one myocardial wall. The primary end point was major adverse cardiovascular events (MACEs), a composite of incident heart failure, myocardial infarction, and stroke. The secondary end point was MACE and revascularization (percutaneous coronary intervention/coronary artery bypass graft). A stenosis ≥70% in one or more coronary arteries defined significant coronary artery disease (CAD; n=107). Patients with significant CAD had a higher prevalence of PSS (55% vs 39%; P<.002), and presence of PSS was an independent predictor of significant CAD in multivariable models adjusted for clinical data, exercise test, and echocardiographic measures (odds ratio, 2.45; 95% CI, 1.08-5.60; P=.033). The PSI confirmed this association (odds ratio, 1.71; 95% CI, 1.04-2.82; P=.034 per 1% increase). During median follow-up of 3.5years (interquartile range, 2.7, 4.1) a total of 25 patients (8.5%) experienced MACE and 46 (15.7%) had the secondary end point. Presence of PSS was a predictor of MACE (hazard ratio, 2.57; 95% CI, 1.12-5.95; P=.028), and the association remained significant in adjusted models. Both presence of PSS and PSI were independent predictors of the secondary end point. In patients with suspected SAP, presence of PSS provides independent diagnostic information on significant CAD and offers novel prognostic information regarding risk of future cardiovascular events.

LAYER-SPECIFIC STRAIN ANALYSIS BY TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY: IMPROVEMENT OF CORONARY ARTERY DISEASE DIAGNOSTICS IN PATIENTS WITH STABLE ANGINA PECTORIS

Background: Novel software allows for layer-specific evaluation of myocardial strain by speckle tracking echocardiography (2DSTE). However, the potential of layer-specific strain at rest for diagnosing coronary artery disease (CAD) in patients with suspected stable angina pectoris (SAP) remains

Vitamin B-6 catabolism and long-term mortality risk in patients with coronary artery disease

Low vitamin B-6 status has been related to increased risk of coronary artery disease (CAD), which is a condition that is associated with inflammation. The most common status marker, plasma pyridoxal 5'-phosphate (PLP), decreases during inflammation; therefore, causal relations are uncertain. We evaluated the vitamin B-6 biomarkers PLP, pyridoxal, and pyridoxic acid (PA) and the pyridoxic acid:(pyridoxal + PLP) ratio (PAr), a proposed marker of vitamin B-6 catabolism during activated cellular immunity, as predictors of mortality. Associations with risks of long-term all-cause mortality and cardiovascular mortality were evaluated with the use of Cox regression in patients who were undergoing elective coronary angiography for suspected stable angina pectoris (SAP) (n = 4131) and an independent cohort of patients who were hospitalized for acute myocardial infarction (AMI) (n = 3665). Plasma PLP (AMI patients only) and PA predicted all-cause mortality in models that were adjusted for established risk predictors, but associations were attenuated or nonsignificant after additional adjustment for inflammatory markers. PAr was correlated with biomarkers of inflammation (Pearson's r ≥ 0.37) and predicted all-cause mortality and cardiovascular mortality after adjustment for established risk predictors. In SAP patients, PAr had greater predictive strength than did current smoking, diabetes, hypertension, apolipoproteins, or C-reactive protein. PAr provided multiadjusted HRs per SD of 1.45 (95% CI: 1.30, 1.63) and 1.31 (95% CI: 1.21, 1.41) in SAP and AMI patients, respectively. In both cohorts, PAr was a particularly strong predictor of all-cause mortality for patients with no previous CAD history (P-interaction ≤ 0.04). PAr may capture unique aspects of inflammatory activation and thus provide new insights into disease mechanisms that may aid in identifying patients at increased risk of future fatal events.

Glycated hemoglobin and long-term prognosis in patients with suspected stable angina pectoris without diabetes mellitus: A prospective cohort study

ObjectiveAssociations of glycated hemoglobin A1c (HbA1c) levels to incident coronary and cardiovascular events among non-diabetic patients with coronary artery disease are unclear. We investigated relations of HbA1c to long-term prognosis in such patients. MethodsA prospective cohort of 2519 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) was divided into pre-defined categories according to HbA1c (%) levels (<5.0, 5.0–5.6 (reference), 5.7–6.4), and followed for median 4.9 years. The primary end-point was major coronary events (including non-fatal and fatal acute myocardial infarctions, and sudden cardiac death). Secondary end-points were death from cardiovascular disease (CVD) and all-cause mortality. Hazard ratios (HRs) (95% confidence intervals [CIs]) were obtained by Cox regression. ResultsMedian age at inclusion was 62 years, 73% were males, median HbA1c was 5.6% and random plasma-glucose 5.4 mmol/L. After multivariate adjustment, HbA1c levels within the pre-diabetic range were not associated with risk of major coronary events, HR (95% CI): 1.13 (0.79–1.62); P = 0.49, death from CVD or all-cause mortality HR (95% CI): 0.95 (0.55–1.66) and 1.04 (0.70–1.53), respectively; P ≥ 0.85. Similarly, there was no significant association between HbA1c values within the lowest category and risk of study outcomes, (P ≥ 0.18). ConclusionIn non-diabetic patients with suspected SAP, there was no overall association between HbA1c levels and prognosis, questioning an independent role of glycemia in the pathogenesis of atherosclerotic complications in these patients.

Elevated plasma dimethylglycine is a risk marker of mortality in patients with coronary heart disease

To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD). By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors. Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and 1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI. Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes.

Predictive value of the corrected TIMI frame count in patients with suspected angina pectoris but no obstructive coronary artery disease at angiography

To evaluate whether the corrected thrombolysis in myocardial infarction frame count (CTFC), an index of resting coronary blood flow, is associated with the risk of major adverse cardiovascular events (MACE) in patients with suspected stable angina pectoris (SAP) but no obstructive coronary artery disease (CAD) at angiography. In this case-control study, CTFC at baseline in 127 patients (50 % women) who subsequently experienced a myocardial infarction, non-hemorrhagic stroke or cardiovascular death during 2001-2011 was compared with CTFC in 254 event-free matched controls. All patients had suspected SAP but no obstructive (≥50 % stenosis) CAD at baseline angiography. Mean CTFC in controls was 23.4 (95 % confidence interval 20.9-25.9) frames and mean CTFC in cases did not differ significantly with a difference of -1.0 (-3.1 to 1.1) frames (P = 0.35) and no sex-specific interaction (P = 0.18). In a conditional logistic regression model, we found no dose-response relationship between CTFC and the risk of MACE, i.e., compared to the risk in the lowest CTFC quintile, the odds ratios for MACE were 1.3 (0.7-2.6), 0.7 (0.3-1.3), 0.7 (0.4-1.5) and 1.0 (0.5-2.1) in the second, third, fourth and fifth CTFC quintiles, respectively. Adjustment for cardiac risk factors including diabetes, active smoking, body mass index, and use of lipid-lowering and antihypertensive medication did not significantly change the results. In patients with SAP symptoms without obstructive CAD at angiography, CTFC is not associated with the risk of MACE.

Myocardial strain analysis by 2-dimensional speckle tracking echocardiography improves diagnostics of coronary artery stenosis in stable angina pectoris

Purpose: To determine if 2-Dimensional Strain Echocardiography (2DSE) performed at rest in patients with suspected Stable Angina Pectoris (SAP) is able to improve the diagnosis of the presence of significant Coronary Artery Disease (CAD). Methods: In total 296 consecutive patients with clinically suspected SAP, no previous cardiac history and a normal ejection fraction were included. All patients were examined by 2DSE, Exercise Electrocardiogram (ECG) and coronary angiography. 2DSE was performed in the three apical projections. Peak Regional Longitudinal Systolic strain (RLS) was measured in 18 myocardial sites and averaged to provide Global Longitudinal Systolic strain (GLS). Duke Score (DS), including ST-depression, chest pain and exercise capacity, was used as the outcome of the exercise ECG. Results: Patients with an area stenosis ≥70% in at least one epicardial coronary artery were categorized as having significant CAD (n=108). GLS was significantly lower in patients with CAD compared to patients without CAD (17.1% vs. 18.8%, p<0.001), and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise ECG and conventional echocardiographic parameters (OR 1.17 (1.0-1.3, p=0.012) per 1% decrease). Area under receiver operating characteristics curve (AUC) for exercise ECG and GLS in combination was significantly higher than AUC for exercise ECG alone (0.84 vs. 0.78, p<0.004). Furthermore, RLS predicted significant stenosis in corresponding coronary arteries (Figure 1). ![Figure][1] Figure 1. RLS in stenotic vs non-stenotic segments Conclusion: In patients with suspected SAP GLS at rest is an independent predictor of significant coronary artery disease and significantly improves the diagnostic performance of exercise ECG. Additionally, RLS can identify which coronary artery that suffers from significant stenosis. [1]: pending:yes

Tissue Doppler echocardiography improves the diagnosis of coronary artery stenosis in stable angina pectoris

Aim To determine if colour tissue Doppler imaging (TDI) performed at rest in patients with suspected stable angina pectoris (SAP) is able to predict the presence of significant coronary artery disease (CAD). This study comprises 296 consecutive patients with clinically suspected SAP, no previous cardiac history, and a normal ejection fraction. All patients were examined by colour TDI, exercise electrocardiogram (ECG), and coronary angiography (CAG). Regional longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured by colour TDI at six mitral annular sites and averaged to provide global estimates. Duke score (DS), including ST depression, chest pain, and exercise capacity, was used as the outcome of the exercise ECG. Patients with an area stenosis of ≥70% in at least one epicardial coronary artery were categorized as having a significant CAD (n= 108) and were compared with patients without significant CAD (n= 188). Both e' [odds ratio (OR): 1.5 (1.1-1.9, P < 0.01) per cm/s decrease] and s' [OR: 1.7 (1.1-2.5, P < 0.05) per cm/s decrease] remained independent predictors of CAD after multivariable adjustment for baseline, exercise ECG, and conventional echocardiographic parameters. Area under the receiver operating characteristic curve (AUC) for exercise ECG and TDI in combination was significantly higher than AUC for exercise ECG alone (0.84 vs. 0.79, P < 0.01). In patients with suspected SAP colour TDI performed at rest is an independent predictor of significant CAD, and colour TDI improves the diagnostic performance of exercise ECG.

Serum osteoprotegerin levels and long-term prognosis in patients with stable angina pectoris

Objectives Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on bone metabolism, endocrine function and the immune system. Circulating OPG levels are elevated in cardiovascular disease (CVD). We assessed serum OPG as predictor of long-term prognosis in patients with suspected stable angina pectoris (SAP) undergoing elective coronary angiography. Methods Samples were obtained from 1025 patients (median [25th, 75th percentile] age 62 [54, 70] years, 71.9% men). At inclusion, 43.2% of patients had single or double vessel disease, whereas 34.3% had triple vessel disease. Results During a median follow-up of 73 months, 11.0% of patients died, 5.9% died from CVD and 10.0% experienced an acute myocardial infarction (MI). In univariable analyses, strong associations were observed between OPG concentrations and all-cause mortality, CVD mortality and the incidence of MI (fatal or nonfatal). However, adjustment for conventional risk factors attenuated the risk estimates which were no longer significant, except for the subgroup with levels above the 90th percentile. For decile 10 versus deciles 1–9 of serum OPG, the following multivariable hazard ratios (95% confidence intervals) were observed: All-cause mortality: 1.94 (1.18, 3.18), p = 0.01; CVD mortality: 2.29 (1.16, 4.49), p = 0.02; and MI: 1.76 (1.02, 3.06), p = 0.04. Conclusion In patients with SAP, elevated serum OPG is associated with increased risk of all-cause mortality, CVD mortality and MI, but independent effects are mainly confined to levels above the 90th percentile.