Joseph Shemesh

Calcium Channel Blocker Nifedipine Slows Down Progression of Coronary Calcification in Hypertensive Patients Compared With Diuretics

Calcium controls numerous events within the vessel wall. Permeability of the endothelium is calcium dependent, as are platelet activation and adhesion, vascular smooth muscle proliferation and migration, and synthesis of fibrous connective tissue. Double-helix computerized tomography is a noninvasive technique that can detect, measure, and compare coronary calcification in the coronary arteries. Using this method, our objective was to determine whether administration of nifedipine once daily in lieu of diuretics in high-risk hypertensive patients will arrest or slow down the progression of coronary artery calcification. The study was designed as a side arm of INSIGHT (International Nifedipine Study: Intervention as Goal for Hypertension Therapy), aimed to show the efficacy of nifedipine once daily versus co-amilozide (hydrochlorothiazide 25 mg, amiloride 2.5 mg) in high-risk hypertensive patients. A total of 201 patients with a total calcium score of ≥10 at the onset of study who underwent an annual double-helix computerized tomography for 3 years were analyzed for efficacy. Inhibition of coronary calcium progression was significant in the nifedipine versus the co-amilozide group during the first year (3.18% versus 27%, respectively, P =0.02), not significant during the second year (28.5% versus 47%, respectively, P =0.14), and significant during the third year (40% versus 78%, respectively, P =0.02). The results point to a slower progression of coronary calcification in hypertensive patients on nifedipine once daily versus co-amilozide.

Ordinal Scoring of Coronary Artery Calcifications on Low-Dose CT Scans of the Chest is Predictive of Death from Cardiovascular Disease

PURPOSE To assess the usefulness of ordinal scoring of the visual assessment of coronary artery calcification (CAC) on low-dose computed tomographic (CT) scans of the chest in the prediction of cardiovascular death. MATERIALS AND METHODS All participants consented to low-dose CT screening according to an institutional review board-approved protocol. The amount of CAC was assessed on ungated low-dose CT scans of the chest obtained between June 2000 and December 2005 in a cohort of 8782 smokers aged 40-85 years. The four main coronary arteries were visually scored, and each participant received a CAC score of 0-12. The date and cause of death was obtained by using the National Death Index. Follow-up time (median, 72.3 months; range, 0.3-91.9 months) was calculated as the time between CT and death, loss to follow-up, or December 31, 2007, whichever came first. Logistic regression analysis was used to determine the risk of mortality according to CAC category adjusted for age, pack-years of cigarette smoking, and sex. The same analysis to determine the hazard ratio for survival from cardiac death was performed by using Cox regression analysis. RESULTS The rate of cardiovascular deaths increased with an increasing CAC score and was 1.2% (43 of 3573 subjects) for a score of 0, 1.8% (66 of 3569 subjects) for a score of 1-3, 5.0% (51 of 1015 subjects) for a score of 4-6, and 5.3% (33 of 625 subjects) for a score of 7-12. With use of subjects with a CAC score of 0 as the reference group, a CAC score of at least 4 was a significant predictor of cardiovascular death (odds ratio [OR], 4.7; 95% confidence interval: 3.3, 6.8; P < .0001); when adjusted for sex, age, and pack-years of smoking, the CAC score remained significant (OR, 2.1; 95% confidence interval: 1.4, 3.1; P = .0002). CONCLUSION Visual assessment of CAC on low-dose CT scans provides clinically relevant quantitative information as to cardiovascular death.

Calcification of the Thoracic Aorta as Detected by Spiral Computed Tomography Among Stable Angina Pectoris Patients. Association With Cardiovascular Events and Death

Background— Calcification of the thoracic aorta is associated with atherosclerotic risk factors, yet its pathogenesis and clinical implications are not yet elucidated. The goal of the present study was to assess whether thoracic aorta calcification is associated with an increased risk of cardiovascular events and death in patients with stable angina pectoris. Methods and Results— A prospective cohort of 361 stable angina pectoris patients (307 men, 54 women; age range, 37 to 83 years) underwent chest spiral computed tomography and were evaluated for aortic calcification. We recorded the incidence of cardiovascular events and death during a 4.5- to 6-year follow-up. Aortic calcification was documented in 253 patients (70% of patients; 213 men, 40 women). Patients with aortic calcification were older (mean age, 65±7 versus 55±9 years; P<0.001), and fewer were classified as smokers (13% versus 26%; P=0.014) compared with patients without aortic calcification. Significant correlation was found between patients with and those without aortic calcification for the presence of aortic valve calcification (28% versus 11%; P<0.001), mitral annulus calcification (29% versus 4%; P<0.001), and coronary calcification as expressed by coronary calcium score. (P<0.001). During 4.5 to 6 years of follow-up, 19 patients died, all of whom were in the aortic calcification group. Age-adjusted hazard ratios for total events and cardiovascular events by aortic calcification were 2.84 (95% CI, 1.52 to 5.30; P=0.001) and 2.70 (95% CI, 1.33 to 5.47; P=0.006), respectively. In multivariable analysis, hazard ratios for total events and cardiovascular events were 2.79 (95% CI, 1.46 to 5.20; P=0.002) and 4.65 (95% CI, 1.19 to 18.26; P=0.028), respectively. Conclusions— Calcification of the thoracic aorta is age related and associated with coronary calcification and valvular calcification. Thoracic aortic calcification is associated with an increased risk of death and cardiovascular disease.

Colchicine for the Prevention of Postpericardiotomy Syndrome

Background: Postpericardiotomy syndrome (PPS) is a troublesome complication of cardiac surgery, occurring in 10–45% of cases. Accepted modalities of treatment include nonsteroidal anti-inflammatory drugs, corticosteroids, and pericardiectomy in severe cases. The optimal method for prevention of PPS has not been established. Recent trial data have shown that colchicine is efficient in the secondary prevention of recurrent episodes of pericarditis. The iam of the present study was to evaluate the possible benefit of colchicine for the primary prevention of PPS in patients after cardiac surgery. To the best of our knowledge, this is the first study addressing this issue. Patients and Methods: A prospective, randomized, double-blind design was used. The initial study group included 163 patients who underwent cardiac surgery in two centers in Israel between October 1997 and September 1998. On the 3rd postoperative day, the patients were randomly assigned to receive colchicine (1.5 mg/day) or placebo for 1 month. All were evaluated monthly for the first 3 postoperative months for development of PPS. Results: 52 of the 163 patients were excluded because of postoperative complications, noncompliance, or gastrointestinal side effects of treatment. Of the 111 patients who completed the study, 47 (42.3%) received colchicine and 64 (57.7%) placebo. There was no statistically significant difference between the groups in clinical or surgical characteristics. PPS was diagnosed in 19 patients (17.1%), 5/47 cases (10.6%) in the colchicine group and 14/64 (21.9%) in the placebo group. The difference showed a trend toward statistical significance (p < 0.135). Conclusions: Colchicine may be efficacious for the prevention of PPS in patients after cardiac surgery. Further evaluations in larger clinical trials are warranted.Hintergrund: Das Postperikardiotomie-Syndrom (PPS) ist eine Folgeerscheinung nach Herzoperationen und tritt bei 10–45% der Patienten auf. Die Behandlung kann mit nichtsteroidalen Entzündungshemmern, Kortikosteroiden und in schweren Fällen durch eine Perikardektomie erfolgen. Ein optimales Verfahren zur Vermeidung des PPS gibt es noch nicht. Neuere klinische Studien zeigten, dass Colchicin bei der Sekundärprävention einer wiederauftretenden Perikarditis wirksam ist. Es war das Ziel der vorliegenden Untersuchung, die Wirkung von Colchicin bei der Primärprävention des PPS zu überprüfen. Eine vergleichbare Untersuchung gibt es unseres Wissens noch nicht. Patienten und Methoden: Die Untersuchung erfolgte prospektiv, randomisiert und doppelblind. In der ursprüglichen Studiengruppe wurden 163 Patienten mit geplanter Herzoperation in zwei Zentren in Israel zwischen Oktober 1997 und September 1998 eingeschlossen. Am 3. postoperativen Tag erhielten die Patienten randomisiert über 1 Monat entweder täglich 1,5 mg Colchicin oder Plazebo. Bei allen Patienten wurde das Auftreten des PPS nach 1, 2 und 3 Monaten überprüft. Ergebnisse: 52 der 163 Patienten wurden wegen postoperativer Komplikationen. Non-Compliance oder gastrointestinalen Nebenwirkungen von der Studie ausgeschlossen. Von den 111 verbliebenen Patienten erhielten 47 (42,3%) Colchicin und 64 (57,7%) Plazebo. Es gab keinen statistisch signifikanten Unterschied in klinischen oder operativen Parametern. Das PPS trat bei insgesamt 19 Patienten (17,1%) auf. In der Colchicin-Gruppe trat es bei 10.6% (5/47) und in der Plazebo-Gruppe bei 21.9% (14/64) der Patienten auf. Der Unterschied war aber nicht statistisch signifikant (p < 0,135). Schlussfolgerung: Weitere klinische Studien sind erfolgreich um die Wirksamkeit von Colchicin bei der Verhinderung des PPS bei Patienten nach Herzoperationen zu sichern.

Comparison of Coronary Calcium in Stable Angina Pectoris and in First Acute Myocardial Infarction Utilizing Double Helical Computerized Tomography

Although coronary calcium is invariably associated with atherosclerosis, its role in the pathogenesis of acute and chronic coronary syndromes remains unclear. Utilizing double helical computerized tomography we evaluated the coronary calcium patterns in 149 patients: 47 with chronic stable angina (SAP) compared with 102 patients surviving a first acute myocardial infarction (AMI). Prevalence of coronary calcium was 81% among the AMI patients and 100% in the stable angina patients. The 547 calcific lesions identified in the AMI patients and the 1,242 lesions in the stable angina patients were categorized into 3 groups according to their extent: mild, intermediate, and extensive. The age-adjusted percentages of the highest level of calcification among AMI versus stable angina patients were: mild 18% vs 3%, intermediate 49% vs 18%, and extensive lesions 33% vs 79%, respectively (p < 0.01). In the AMI group, 73 culprit arteries were identified: 16 (22%) had no calcium detected, whereas 30 (41%) had mild lesions, 20 (27%) had intermediate forms, and only 7 (10%) had extensive lesions. The age-adjusted mean of the natural logarithm transformation of total calcium scores +1 was significantly lower in patients with AMI than in those with SAP (4.1 [95% confidence interval 3.7 to 4.4) vs 5.3 [95% confidence interval 4.8 to 5.8]). Thus, double helical computerized tomography demonstrates that extensive calcium characterizes the coronary arteries of patients with chronic stable angina, whereas a first AMI most often occurs in mildly calcified or noncalcified culprit arteries.

Usefulness of colchicine in preventing recurrences of pericarditis

ventricular exeasystoles and beta-blocking agents. .I Irish Med Assoc 1975;68: 369-375. 2. Abinader EG. Adrenergic beta blockade and ECG changes in the systolic click murmur syndrome. Am Heart J 1976;91:297-302. 3. Abinader EG, Shahar J. Exercise testing in mitral valve prolapse before and afta beta blockade. Br Hearr J 1982;48:130-133. 4. Abmader EG. Clinical considerations in interpretation of the exercise electmcardiogram in the patient with mitral valve prolapse. Pracr Cardiol1983;9: 172-l 8 1. 5. Abmader EG. ‘Ihe effect of beta blockade on the abnormal exercise test in patients with mitral valve prolapse. J Cardiac Rehbil 1984;4:95-100. 6. Deanfield JE, Shea M, Ribezio P, Laodsheere CM, Wilson RA, Horlock P, Selwyn AP. Transient ST-segment depression as a marker of myocardial ischemia during daily life. Am J Cardiol 1984;s 1195-1200. 7. h39:39&402. 8. Imperi GA, Lambert CR, Coy K, Lopez L, Pepine CL. Effects of titrated betablockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease. Am J Cardiol 1987;60519-524. 9. Hill JA, Gonzalez JI, Kolob R, Pepine Cl. Effects of atenolol alone, nifedipine alone and their combination on ambulant myocardial ischemia. Am J Cardioll991; 67:671675. 10. Mulcahy D, Keegan I, Cunningham D, Quyyumi A, Crean P, Park A, Wright C, Fox K. Circadian variation of total ischemic burden and its alteration with antianginal agents. Lancet 1988;2:755-759. ll. Boudoulas H, Reynolds JC, Mazzaferri E, Wooley CF. Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine-cardiovascular process. Circulation 1980;61:1200-1205. 12. Pastemac A, Tubau JF, Puddu PE, Krol RB, De Champlain J. Increased plasma catecholamines in symptomatic mitral valve prolapse. Am J Med 1982; 73:783-790. 28. Bertolet BD, Boyette AF, Hofmann CA, Pepine CJ, Hill JA. Prevalence of pseudoischemic ST-segment changes during ambulatory elecuocardiographic monitoring. Am J Cardiol 1992;70:818-820. l4. The ACIP Investigators. Asymptomatic cardiac ischemia pilot study (ACIP). Am J Cardiol 1992;10:744-741.

Coronary Artery Disease but Not Coronary Calcification Is Associated with Elevated Levels of Cardiolipin, Beta-2-Glycoprotein-I, and Oxidized LDL Antibodies

Background: Autoimmune factors have been shown to play a role in atherosclerosis. The aim of this study is to correlate 5 autoantibodies (anticardiolipin, anti-CL, β2-glycoprotein-I, β2GPI, phosphatidylcholine, oxidized low-density lipoprotein, oxLDL, endothelial cell) with the presence of coronary heart disease, angiographic findings, and with coronary artery calcification. Methods: The levels of the 5 autoantibodies and a control antifibroblast line of 126 coronary heart disease patients and 20 healthy controls were measured. Fifty-one patients underwent coronary angiography, and 98 patients had coronary artery calcium determination using spiral computerized tomography (dual mode). Results: Levels of 3 autoantibodies (anti-CL, β2GPI, oxLDL) were significantly elevated in coronary heart disease patients compared with controls (p < 0.001,p = 0.001, p < 0.001, respectively). Within the subgroup of patients with significant coronary artery stenosis, anti-CL antibodies were also elevated (p = 0.008). No correlation was found between anti-CL, and anti-β2GPI autoantibody levels and coronary calcium scores as measured by spiral computerized tomography. However, anti-oxLDL antibodies were raised in patients with no calcification detected by spiral computerized tomography, compared with the patients with any coronary calcification (p = 0.046). Conclusion: Anti-CL, β2GPI and oxLDL antibodies are elevated in coronary heart disease patients regardless of coronary calcification.

Menopause-induced changes in Doppler-derived parameters of aortic flow in healthy women

Currently, estrogen replacement therapy is widely used as a specific treatment for hypoestrogenic associated conditions such as vasomotor instability, genitourinary atrophy and osteoporosis. These conditions affect a substantial number of postmenopausal women.1 The favorable effects of estrogen replacement therapy on cardiac morbidity and mortality in postmenopausal women have usually been attributed to an improved lipid profile. 2–4 It is now accepted that other mechanisms, such as the direct effect of estrogens on coronary vasculature and atherosclerotic plaque, may also have an important role in cardioprotection.3–5 Using Doppler echocardiography we recently demonstrated a significant increase in aortic flow velocity and acceleration after 10 weeks of hormone replacement therapy.6 These findings led us to investigate whether menopause and the related decrease in estrogen levels were associated with changes in Doppler-derived parameters of aortic flow.

Coronary calcium by spiral computed tomography predicts cardiovascular events in high-risk hypertensive patients.

Objective The ability of coronary artery calcium (CAC) to predict coronary events has been shown in several studies. We aimed to investigate the hypothesis that CAC as assessed by dual slice spiral computed tomography (DSCT), is an independent risk factor for cardiovascular events in hypertensive patients. Methods We followed 446 participants of INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy) calcification study, for the incidence of cardiovascular events as a function of CAC and other factors. All were hypertensive, without coronary artery disease (CAD), ages > 55 years and with at least one more major cardiovascular risk factor. All underwent a baseline DSCT and were followed for a mean period of 3.8 ± 0.4 years. All events were documented while the scheduled visits and confirmed by the INSIGHT critical event committee. Results Follow-up was conducted on all participants. 294 patients (66%) had CAC at baseline. Forty-seven patients experienced a first cardiovascular event: acute myocardial infarction (MI), 16; sudden cardiac death, two; unstable angina resulting in revascularization, 14; stroke, 15. The incidence of first cardiovascular events was 3.7 times higher among those who had CAC at baseline than among those who had no CAC (14.5% (41 of 294) versus 3.9% (6 of 152)). Patients who experienced an event were more likely to be males, had had higher prevalence of peripheral vascular disease, longer duration of hypertension, and had higher levels of systolic blood pressure (SBP), glucose, creatinine and uric acid. Adjusting for these covariates, CAC (total coronary calcium score (TCS) > 0) independently predicted cardiovascular events with an odds ratio (OR) of 2.76 [95% confidence interval (CI) 1.09–6.99, P = 0.032]. Conclusion The presence of CAC predicts cardiovascular events in high-risk asymptomatic hypertensive patients.

Ventricular arrhythmias in rehabilitated and nonrehabilitated post-myocardial infarction patients with left ventricular dysfunction

The incidence of ventricular arrhythmias in rehabilitated post-myocardial infarction (MI) patients with left ventricular dysfunction included in a long-term rehabilitation program was assessed and compared with that in similar patients who were not in such a program. Thirty-eight post-MI patients (2 to 19 years after the acute event) with ejection fraction < 40% were investigated by 48-hour Holter monitoring. They were divided into the following 3 groups: group I, 11 patients who underwent arm training for 60 months; group II, 11 patients who underwent calisthenics for 36 months; and group III, 16 patients who were not in any rehabilitation program; the age of the patients was 61 +/- 7, 61 +/- 6 and 61 +/- 9 years, respectively, (p = not significant). Ejection fraction at rest was 31 +/- 9 for group I, 29 +/- 7 for group II, and 29 +/- 7 for group III (p = not significant). There were no significant differences concerning the location of MI, and antiarrhythmic treatment received by patients from all groups. At the conclusion of 48-hour Holter monitoring, 2 blood samples were obtained for assessment of norepinephrine (at rest and after postural change). Quality of life was determined by a detailed questionnaire, including questions concerning social activity, life satisfaction and sexual function. After 36 and 60 months, an improvement in hemodynamic condition of patients in group I was noted. Quality of life was higher in the rehabilitated patients, with enhanced emotional stability, satisfaction with work and social life, and a high percentage of return to work (82 vs 40%).(ABSTRACT TRUNCATED AT 250 WORDS)