Revascularisation of coronary artery disease in patients with diabetes mellitus

Diabetes mellitus is becoming increasingly prevalent and magnifies the risk of cardiovascular complications. Endothelial dysfunction caused by oxidative stress is a hallmark of diabetes and is responsible for the ubiquitous manifestations of vascular disease in diabetics. Compared with non-diabetic patients, coronary artery disease is more severe and the clinical outcome impaired in diabetic patients undergoing revascularisation. Despite these limitations the benefit of revascularisation therapy is particularly pronounced in diabetics. The optimal revascularisation strategy (coronary artery bypass graft surgery versus percutaneous coronary intervention) in diabetic patients with coronary artery disease depends on clinical and anatomical considerations.

Non-invasive diagnosis of coronary artery disease using cardiogoniometry performed at rest

PRINCIPLES: Cardiogoniometry is a non-invasive technique for quantitative three-dimensional vectorial analysis of myocardial depolarization and repolarization. We describe a method of surface electrophysiological cardiac assessment using cardiogoniometry performed at rest to detect variables helpful in identifying coronary artery disease. METHODS: Cardiogoniometry was performed in 793 patients prior to diagnostic coronary angiography. Using 13 variables in men and 10 in women, values from 461 patients were retrospectively analyzed to obtain a diagnostic score that would identify patients having coronary artery disease. This score was then prospectively validated on 332 patients. RESULTS: Cardiogoniometry showed a prospective diagnostic sensitivity of 64%, and a specificity of 82%. ECG diagnostic sensitivity was significantly lower, with 53% and a similar specificity of 75%. CONCLUSIONS: Cardiogoniometry is a new, noninvasive, quantitative electrodiagnostic technique which is helpful in identifying patients with coronary artery disease. It can easily be performed at rest and delivers an accurate, automated diagnostic score.

[Pharmacotherapy in coronary artery disease]

With the exception of anticoagulant therapy this article reviews pharmacotherapy for patients with coronary artery disease based on indications, clinical trials and current guidelines. Mechanisms of action, contraindications, and interactions are reviewed in this article. Only an appropriate use of available drugs according to guidelines permits to achieve the best relation of benefit and risk.

[Coronary artery disease - definitions and epidemiology]

Over the past two centuries, coronary artery disease has emerged as an important cause of morbidity and death in industrialized nations. Increased life expectancy and changed habits (regarding nutrition, physical activity, and smoking) have contributed to this dramatic epidemiologic shift. During the last 50 years, a decline in the coronary artery disease mortality rate was observed due to therapeutic advances and prevention measures targeted at people with coronary artery disease and those potentially at risk for it. This article highlights important epidemiologic data and some definitions in the context of coronary artery disease are presented.

Prevalence of type 2 diabetes is higher in peripheral artery disease than in coronary artery disease patients.

Type 2 diabetes mellitus and pre-diabetes are risk factors for atherosclerosis and are highly prevalent in patients with coronary artery disease. However, the prevalence of impaired glucose metabolism in patients with peripheral artery disease is not as well elucidated. We aimed at comparing prevalence rates of type 2 diabetes mellitus and pre-diabetes, which were diagnosed according to the current American Diabetes Association criteria, among 364 patients with peripheral artery disease, 529 patients with coronary artery disease and 383 controls. The prevalence of type 2 diabetes mellitus in peripheral artery disease patients was 49.7%. It was significantly higher in these patients than in coronary artery disease patients (34.4%; p < 0.001) and controls (21.4%; p < 0.001). Adjusted for sex, age and body mass index, odds ratios for type 2 diabetes mellitus were 2.0 (95% confidence interval 1.5-2.6) comparing the peripheral artery disease group with the coronary artery disease group (p < 0.001) and 4.0 (2.8-5.8) comparing the peripheral artery disease group with controls (p < 0.001). The prevalence of pre-diabetes among non-diabetic subjects was high in all three study groups (64.5% in peripheral artery disease patients, 63.4% in coronary artery disease patients and 61.8% in controls), without significant between-group differences. In conclusion, the prevalence of type 2 diabetes mellitus is even higher in peripheral artery disease patients than in coronary artery disease patients. This observation underlines the need to consider impaired glucose regulation in the management of peripheral artery disease.

Beneficial effect of recruitable collaterals: a 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements

BACKGROUND: The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. METHODS AND RESULTS: Eight-hundred forty-five individuals (age, 62+/-11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure-derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: CFI = (P(occl) - CVP)/(P(ao) - CVP) where P(occl) is mean coronary occlusive pressure, P(ao) is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CFI < 0.25) or well-grown collateral vessels (CFI > or = 0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI (P=0.0395, P=0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking. CONCLUSIONS: A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.

The prevalence of endothelial dysfunction in patients with and without coronary artery disease

Endothelial dysfunction (ED) is frequently present in patients presenting with acute or stable coronary artery disease (CAD), but it is also found in patients presenting with chest pain without angiographic coronary lesions.

Impact of coronary artery disease and percutaneous coronary intervention on outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation

Coronary artery disease (CAD) is frequently present in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). While revascularisation affects peri-operative outcome in patients undergoing surgical aortic valve replacement, the impact of percutaneous coronary intervention (PCI) in patients undergoing TAVI is not well established.

Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; Results from the heart quest cohort study

The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective cohort. This study is aimed to identify the cause of angina in these patients.

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

AIMS/HYPOTHESIS: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. METHODS: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. RESULTS: RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA(1c) in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. CONCLUSIONS/INTERPRETATION: RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.

High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men

OBJECTIVE: Adiponectin has anti-atherogenic properties and low circulating adiponectin has been linked to coronary atherosclerosis. Yet, there is considerable evidence that the high-molecular weight (HMW) complex of adiponectin is the major active form of this adipokine. We therefore investigated whether HMW adiponectin is associated with the extent of coronary artery disease (CAD) in men. RESEARCH DESIGN AND METHODS: Associations among CAD, HMW adiponectin and the HMW/total-adiponectin ratio were assessed in 240 male patients undergoing elective coronary angiography. Total adiponectin and HMW adiponectin was measured by enzyme-linked immunosorbent assay and serum levels were correlated with defined coronary scores and established cardiovascular risk factors. RESULTS: We found significant inverse correlations between angiographic scores and HMW adiponectin [Extent Score (ES): r=-0.39; Gensini Score (GS): r=-0.35; and Severity Score (SS): r=-0.40, all P<0.001], and the HMW/total-adiponectin ratio (ES: r=-0.49; GS: r=-0.46; SS: r=-0.46; all P<0.001). Multivariable regression analyses revealed that HMW adiponectin and the HMW/total-adiponectin ratio were significantly associated with the extent of CAD (both P<0.001). ROC analyses demonstrated that the predictive value of HMW adiponectin and the HMW/total-adiponectin ratio for the extent of coronary atherosclerosis significantly exceeded that of total adiponectin (P<0.001, P=0.010, respectively). CONCLUSIONS: HMW adiponectin and the HMW/total-adiponectin ratio inversely correlate with the extent of CAD. HMW adiponectin in particular seems to be a better marker for CAD extent than total adiponectin.

Association of lipopolysaccharide-binding protein and coronary artery disease in men

OBJECTIVES: In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as a biomarker for coronary artery disease (CAD). BACKGROUND: The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain unclear. Lipopolysaccharide-binding protein is the first protein to encounter lipopolysaccharide and to deliver it to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates activation of innate immune responses. METHODS: A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary atherosclerosis was assessed by 2 established scores: "extent score" and "severity score." Levels of LBP, markers of inflammation, and traditional risk factors for CAD were assessed. RESULTS: Serum LBP concentration was significantly increased in 172 patients with angiographically confirmed CAD compared with 75 individuals without coronary atherosclerosis (20.6 +/- 8.7 pg/ml vs. 17.1 +/- 6.0 pg/ml, respectively; p = 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk factors and markers of systemic inflammation, LBP was a significant and independent predictor of prevalent CAD (p < 0.05 in all models). CONCLUSIONS: Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the data and to identify pathogenetic links between innate immune system activation and atherosclerosis.

Relation of depression to various markers of coagulation and fibrinolysis in patients with and without coronary artery disease

BACKGROUND: It has been suggested that changes in blood coagulation and fibrinolysis might explain the observed association between depression and coronary artery disease (CAD). So far, only a few coagulation factors have been investigated in this regard, and the results were not consistent. DESIGN: The aim of our study was to analyse a broad range of coagulation and fibrinolytic factors, with emphasis on factors directly involved in clot formation and degradation or reflecting coagulation activation, in patients with CAD and controls without CAD, as assessed by coronary angiography, who also underwent a diagnostic procedure for depression. METHODS: We screened 306 patients with CAD and controls without CAD for depression using the Hospital Anxiety and Depression Scale and Allgemeine Depressions Skala-L questionnaires. In participants with positive screening result, diagnosis of major depression was confirmed or excluded by a structured interview. We analysed the following coagulation and fibrinolytic factors: fibrinogen, prothrombin fragment F1+2, factor XIII A-subunit, factor XIII B-subunit, tissue plasminogen activator, plasminogen activator inhibitor-1, thrombin-activable fibrinolysis inhibitor, and D-dimer. RESULTS: We did not observe significant associations between depression and CAD, nor between depression and cardiovascular risk factors. Coagulation and fibrinolytic factors showed no differences between patients with CAD and controls, but they were associated with several cardiovascular risk factors. Depression was not associated with coagulation and fibrinolytic factors. No associations were found either when both CAD and depression were taken into account. CONCLUSION: Our study gives no evidence that there is a significant relation among depression, CAD, and blood coagulation and fibrinolysis.

Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT

PURPOSE: To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS: All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS: A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION: Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.