Angiotension-converting enzyme gene I/D polymorphism in patients with angina and normal coronary arteriograms.
ABSTRACT A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).
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ABSTRACT: The D allele of the angiotensin-converting enzyme (ACE) I/D polymorphism is associated with elevated levels of serum and tissue ACE, increased production of the vasopressor angiotensin II and a reduction in the half-life of the vasodilator bradykinin. Several cardiac and renal conditions appear to have a worse prognosis in subjects homozygous for the D allele, whereas the I allele has been associated with enhanced endurance performance in elite distance runners, rowers and mountaineers. The nature of the gene–envirnoment interaction between ACE I/D polymorphisms and physical training, an overview of recent findings and a discussion of possible underlying mechanisms is the subject of this review.Trends in Endocrinology and Metabolism 01/2001; · 8.90 Impact Factor
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ABSTRACT: Objectives. This study was conducted to test the hypothesis that angiotensin-converting enzyme inhibition may lessen myocardial ischemia in patients with microvascular angina.Background. Patients with syndrome X (angina pectoris, positive findings on exercise testing and normal coronary arteriogram) have reduced coronary vasodilator reserve (“microvascular angina”, and may show an increased sympathetic drive. Angiotensin-converting enzyme inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.Methods. Ten patients (seven women and three men, mean age [±SD] 53 ± 6 years) with syndrome X and a reduced coronary flow reserve underwent a randomized, single-blind, crossover, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on angina and exercise-induced ST segment depression. Assessment was by symptom-limited treadmill exercise testing after 2 weeks of treatment with 10 mg/day of enalapril and after 2 weeks of placebo administration.Results. All patients had positive findings on exercise testing (≥1 mm ST segment depression and angina) white taking placebo, whereas six patients had a positive test results (four with angina) during enalapril therapy. Total exercise duration and time to 1 mm of ST segment depression were prolonged by enalapril over those obtained with placebo (mean 779 ± 141 vs. 690 ± 148s, p = 0.006 and 690 ± 204 vs. 485 ± 241 s, p = 0.007, respectively). The magnitude of ST segment depression was also less with enalapril than with placebo (mean 1.1 ± 0.4 vs. 1.5 ± 0.2 mm, p = 0.004). Heart rate and blood pressure at peak exercise and at 1 mm of ST depression were not significantly different during placebo and enalapril treatment.Conclusions. Angiotensin-converting enzyme inhibition lessens exercise-induced ischemia in patients with syndrome X and microvascular angina, probably by a direct modulation of coronary microvascular tone, which results in an increased myocardial oxygen supply.Journal of the American College of Cardiology 03/1994; · 14.09 Impact Factor
Article: Development of a fatigue scale.[show abstract] [hide abstract]
ABSTRACT: A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two-factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5.Journal of Psychosomatic Research 02/1993; 37(2):147-53. · 3.27 Impact Factor