Ian D. Cox

Cardiac troponin elevations in chronic renal failure: prevalence and clinical significance.

OBJECTIVES The aim of the study was investigate the prevalence of abnormal values of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in patients with chronic renal failure (CRF) and their clinical significance. DESIGN AND METHODS We investigated the concentrations of cTnT and cTnI in 49 CRF patients without heart disease or diabetes. Cardiac TnT values were measured with a second generation immunoassay and cTnI with two immunoassays with different analytical sensitivity. All CRF patients underwent regular clinical follow-up over a 18-month period. RESULTS No patients with CRF had elevated values of cTnI when measured with one assay and only 2 patients displayed minimally elevated values with the second assay. In contrast, 23 CRF patients (47%) displayed cTnT concentrations elevated above the upper reference limit. The elevated cTnT values observed were below the values detected in acute myocardial infarction and were not associated with adverse cardiac events during follow-up. CONCLUSIONS Mildly elevated cTnT concentrations are common in patients with CRF and do not appear to be associated with adverse coronary events.

Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms

OBJECTIVES The purpose of this study was to investigate the relationship between arterial and coronary sinus endothelin (ET) concentrations and coronary vasomotor responses during rapid atrial pacing in patients with chest pain and normal coronary arteriograms (CPNA). BACKGROUND Plasma ET concentrations are significantly higher in CPNA patients than in healthy control subjects. METHODS We investigated 19 carefully characterized CPNA patients (14 women; mean age 53 +/- 9 years) of whom 10 had positive electrocardiographic responses to exercise. The percentage fall in coronary vascular resistance (%d.CVR) after 10 min of rapid atrial pacing was determined using a thermodilution pacing catheter. Plasma ET concentrations were measured by radioimmunoassay on simultaneously drawn arterial and coronary sinus samples. RESULTS No significant differences in ET concentrations were observed between men and women, but a strong statistical trend suggested that %d.CVR was lower in women than men (27[23 to 31]% vs. 34[29 to 45]%--median[interquartile range]; p = 0.07). Simple regression analysis including only the women (n = 14) suggested a significant relationship between baseline arterial ET concentrations and %d.CVR (R2 = 0.34; p = 0.06). Furthermore, stepwise multivariate regression analysis of the group as a whole indicated that both gender (p = 0.03) and baseline arterial ET concentration (p = 0.02) were independently predictive of %d.CVR (R2 = 0.44; overall p = 0.02); this relationship predicts that women with high ET levels would have the lowest %d.CVR during pacing. CONCLUSIONS These data support the hypothesis that elevated ET activity may be associated with reduced coronary flow responses during rapid atrial pacing in CPNA patients.

Elevated Plasma Lipoprotein(a) Is Associated With Coronary Artery Disease in Patients With Chronic Stable Angina Pectoris

OBJECTIVES We sought to assess the relation between plasma lipoprotein(a) [Lp(a)] levels, clinical variables and angiographic coronary artery disease (CAD) in patients with chronic stable angina. BACKGROUND The relation between plasma Lp(a) levels and the severity and extent of angiographic CAD has not been studied in well characterized patients with stable angina pectoris. METHODS We investigated clinical variables, lipid variables and angiographic scores in 129 consecutive white patients (43 women) undergoing coronary angiography for chronic stable angina. RESULTS Plasma Lp(a) levels were significantly higher in patients with than in those without significant angiographic stenoses (> or =70%) (372 mg/liter [interquartile range 87 to 884] vs. 105 mg/liter [interquartile range 56 to 366], respectively, p=0.002). This difference remained significant when patients with mild or severe angiographic disease were compared with those with completely normal coronary arteries (312 mg/liter [interquartile range 64 to 864] vs. 116 mg/liter [interquartile range 63 to 366], respectively, p=0.02). However, subset analysis indicated that this difference achieved statistical significance only in women. Multiple logistic regression analysis indicated that Lp(a) concentration was independently predictive of significant angiographic stenoses (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 2.0 to 42.1, p=0.006) and remained true even after exclusion of patients receiving lipid-lowering treatment (n=27) (OR 10.4, 95% CI 1.1 to 102.9, p=0.05). Lp(a) also had independent predictive value in a similar analysis using mild or severe angiographic disease as the outcome variable (OR 11.8, 95% CI 1.5 to 90.8, p=0.02). CONCLUSIONS Our results indicate that elevated plasma Lp(a) is an independent risk factor for angiographic CAD in chronic stable angina and may have particular significance in women.

Differential plasma endothelin levels in subgroups of patients with angina and angiographically normal coronary arteries

BACKGROUND Raised plasma endothelin concentrations have previously been reported in patients with cardiac syndrome X, but it is not known whether these levels vary between clinically distinct subgroups in this heterogeneous condition. METHODS AND RESULTS We compared plasma immunoreactive endothelin levels in 54 patients with angina pectoris and normal coronary angiograms and 21 healthy control subjects. The patient group was divided into 4 clinically distinct subgroups: 7 with left bundle branch block (group A); 7 with previous myocardial infarction (group B); 24 with positive exercise electrocardiography (group C); and 16 with negative exercise electrocardiography (group D). The plasma endothelin concentration was significantly higher in patients compared with control subjects (3.7 [2.9 to 4.3] vs 2.96 [2.4 to 3.4] pg/mL, respectively, median [interquartile range]; P=0.002). Endothelin concentrations were most significantly elevated in group A and group B (4.5 [3.6 to 5.2] pg/mL; P=0.005 and 4.1 [3.9 to 4.5] pg/mL; P=0.001, respectively). Plasma endothelin concentrations were also significantly elevated in group C (3.7 [2.8 to 4.1] pg/mL; P=0.02) but not in group D (3.0 [2.5 to 3.8] pg/mL; P=0.3). CONCLUSIONS Plasma endothelin concentration is elevated in patients with angina pectoris and angiographically normal coronary arteries, particularly those with left bundle branch block or previous myocardial infarction.

Serum Endothelin Levels and Pain Perception in Patients With Cardiac Syndrome X and in Healthy Controls

The possible algogenic effects of elevated serum endothelin levels in cardiac syndrome X were investigated in a case-control study that examined somatic pain perception in the forearm during submaximal effort tourniquet and cold immersion tests. Pain threshold to both ischemic and cold stimulation of the forearm was demonstrated to be significantly lower in patients with syndrome X than in matched healthy controls, and a negative correlation between ischemic pain threshold and endothelin levels was demonstrated.

Endothelin: An Important Mediator in the Pathophysiology of Syndrome X?

Angina pectoris with normal coronary arteries is a common clinical entity with up to 30% of patients undergoing invasive assessment for anginal chest pain having normal coronary angiograms [1,2]. The term cardiac syndrome X to describe patients with chest pain and normal coronaries was first introduced by Kemp in 1973 [3] and is now generally confined to patients with exertional angina, completely normal coronary angiograms and a positive electrocardiographic response (> 0.1 mV of ST segment depression) to exercise testing [4]. The pathophysiology of chest pain in this patient group appears to be heterogeneous and remains the subject of considerable debate [5, 6, 7]. A non-cardiac source of pain, often originating in the gastrointestinal or musculoskeletal system, may be identified by further investigation. However, around 20% of patients appear to have objective evidence of myocardial ischemia in most series, and a mechanism involving a primary cardiac abnormality remains the most likely explanation for the symptoms in this subgroup.

The pathology and pathophysiology of coronary artery disease

Atherosclerosis is by far the most common and clinically important condition to affect the coronary arteries, causing 127,000 deaths due to myocardial infarction in the United Kingdom each year. Consequently, the terms coronary artery disease and coronary atherosclerosis are often used synonymously although a variety of other pathological processes may affect the coronaries. This chapter will concentrate on the pathophysiology of coronary atherosclerosis with particular emphasis on the relationship between the natural history of atherosclerotic disease progression and the evolution of clinical disease. The pathophysiology of other forms of coronary disease will not be covered.