Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by antioxidant vitamins.

OBJECTIVE: To evaluate the effect of acute hyperhomocysteinaemia with and without antioxidant vitamins pretreatment on coronary circulation and circulating chemokine levels. DESIGN: Observer-blinded, randomized crossover study. SETTING: This study was conducted at a university hospital and at a general hospital in Italy. SUBJECTS: Sixteen healthy hospital staff volunteers (nine men, seven women), aged 26-40 years. INTERVENTIONS: Subjects were given each three loads in random order at 1-week intervals: oral methionine, 100 mg kg(-1) in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). MAIN OUTCOME MEASURES: Coronary flow velocity reserve (CFVR), assessed by noninvasive transthoracic Doppler echocardiography, blood pressure, heart rate, lipid and glucose, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) parameters evaluated at baseline and 4 h following ingestion of the loads. RESULTS: The oral methionine load increased plasma homocysteine from 12.8 +/- 1.8 to 33.3 +/- 3.4 micromol L(-1) at 4 h (P < 0.001). A similar increase was observed with same load plus vitamins (P < 0.001) but not with placebo (P = 0.14). Circulating MCP-1 and IL-8 levels rose after the methionine load (P < 0.001), but not after placebo or methionine plus vitamins. The methionine load significantly reduced CFVR (decrease, 26 +/- 8.2%; P < 0.001). The methionine load with ingestion of vitamins partially prevented the impairment of CFVR (decrease, 11 +/- 4%; P < 0.001). CONCLUSION: Our data suggest that acute hyperhomocysteinaemia reduces CFVR and increases plasma MCP-1 and IL-8 levels in healthy subjects. Pretreatment with antioxidant vitamin E and ascorbic acid prevents the effects of hyperhomocysteinaemia, suggesting an oxidative mechanism.

[The echo-stress test with dipyridamole-atropine on the 3rd-5th day of an uncomplicated acute myocardial infarct for risk stratification and early discharge]. / Eco-stress con dipiridamolo-atropina in terza-quinta giornata nell'infarto miocardico acuto non complicato per la stratificazione del rischio e la dimissione precoce.

BACKGROUND: The aim of this study was to evaluate if dipyridamole-atropine stress echocardiography (DASE) performed between the third-fifth day in uncomplicated acute myocardial infarction allows for an effective risk stratification with an early discharge in some cases. METHODS: Between February 1997 and September 1998, 190 patients (138 males and 52 females, mean age 59 +/- 10.3 years), with acute myocardial infarction, were enrolled in the study. DASE was performed between the third-fifth day with a dipyridamole infusion of 0.84 mg/kg over 10 min followed by 1 mg of atropine from the twelfth to the fifteenth minute. DASE was considered positive in the presence of a new or worsening dyssynergy. Patients with heart failure, angina, major arrhythmias, and poor acoustic window were excluded. In the follow-up spontaneous events were defined as cardiac death, non-fatal myocardial reinfarction, unstable angina or heart failure (with hospitalization). RESULTS: DASE was performed in 92 patients (48.4%), all without complications: 29 patients (31.5%) had a negative DASE result, and 63 patients (68.5%) had a positive DASE. The average hospital stay of patients with a negative test was significantly lower in comparison with that of patients with a positive test (7.55 +/- 1.32 vs 9.29 +/- 1.61 days, p < 0.0001). Events occurred in 19 patients (20.6%), 2/29 patients with a negative DASE (6.9%), 17/63 patients with a positive DASE (27%), 6/43 patients with homozonal positivity after atropine or high-dose dipyridamole (14%), 11/20 patients with heterozonal positivity or homozonal positivity after low-dose dipyridamole (55%). On univariate analysis the variables significantly associated with spontaneous events were: age (chi 2 = 6.41, p = 0.019), left ventricular ejection fraction at rest (chi 2 = 8.89, p = 0.004), number of asynergic segments after stress (chi 2 = 6.87, p = 0.010), increase in the number of asynergic segments after stress (chi 2 = 4.01, p = 0.039), wall motion score index after stress (chi 2 = 9.60, p = 0.003), increase in wall motion score index after stress (chi 2 = 3.60, p = 0.049), DASE positivity (chi 2 = 4.89, p = 0.029), homozonal positivity after low-dose dipyridamole (chi 2 = 8.57, p = 0.013), heterozonal positivity (chi 2 = 13.10, p = 0.001). On Cox's multivariate analysis independent predictors of events were: age (relative risk 3.92, p = 0.0146), DASE positivity (relative risk 1.79, p = 0.0054). CONCLUSIONS: DASE between the third-fifth day in uncomplicated acute myocardial infarction is feasible, tolerable, safe, and effective for early risk stratification. A negative DASE detects a "very low-risk" patient group, and allows for an earlier hospital discharge, without an increased risk of events. The heterozonal positivity or the homozonal positivity after low-dose dipyridamole indicates the need for a coronarography, due to the high risk of events at follow-up.

[Syncopal vasospastic angina in a patient with familial nonobstructive hypertrophic cardiomyopathy]. / Angina vasospastica sincopale in paziente con cardiomiopatia ipertrofica non ostruttiva familiare.

We describe an unusual case of a 51-year-old woman affected with familial non-obstructive cardiomyopathy and syncopal vasospastic angina. The use of hyperventilation stress-echo testing, recommended by the authors because of its simplicity and safety, was decisive in showing the causal role of coronary spasm of the left anterior descending artery. The coronarography had not shown obstructive lesions of the coronary arteries, but during the procedure the patient had refused ergonovine or acetylcholine injections.

[Dipyridamole-echocardiography and thallium exercise myocardial scintigraphy in the diagnosis of obstructive coronary or microvascular disease in hypertensive patients with left ventricular hypertrophy and angina]. / Eco-dipiridamolo e miocardioscintigrafia da sforzo al tallio nella diagnosi di coronaropatia ostruttiva o malattia microvascolare in pazienti ipertesi con ipertrofia ventricolare sinistra e angina.

BACKGROUND: Hypertensive patients with left ventricular hypertrophy can be affected with angina pectoris for significant epicardial coronary stenosis or microvascular disease with normal coronarography. Exercise-electrocardiography test is positive in both conditions. The aim of the present study was to assess the accuracy of dipyridamole-echocardiography test and thallium exercise myocardial scintigraphy in the diagnosis of epicardial coronary stenosis or microvascular disease in hypertensive patients with left ventricular hypertrophy and angina pectoris. METHODS: Forty-two hypertensive patients (22 males, age 40-76 years, mean 58.6 +/- 10.1), with left ventricular hypertrophy, typical angina pectoris, ischemia that can be induced by exercise-electrocardiography test, without previous myocardial infarction, myocardial revascularization or diabetes mellitus, underwent dipyridamole-echocardiography test, thallium exercise myocardial scintigraphy and coronarography. Dipyridamole-echocardiography test was performed with dipyridamole (0.56 mg/kg over 4 minutes, followed by 0.28 mg/kg from the 8th to the 10th minute) + atropine (1 mg from the 12th to 15th min.) and was positive for a transient dyssynergy of contraction of at least 2 myocardial segments; the left ventricle was divided into 16 segments. SPECT thallium myocardial scintigraphy was performed after bicycle exercise and then three hours later, and it was positive for reversible uptake defects of at least 2 segments with a 22-segment model. Coronarography was performed with Judkin's technique and was positive if at least one large epicardial vessel was narrowed by more than 50%. RESULTS: Coronarography: normal in 25 cases (59.5%, 8 males), pathologic in 17 (40.5%, 14 males): left main coronary artery in 1 (5.9%), three vessels in 5 (29.4%), two vessels in 3 (17.7%), 1 vessel in 8 (47%). Dipyridamole-echocardiography-test: positive in 15 cases (35.7%), negative in 27 (64.3%); sensitivity 88.2%, specificity 100%, diagnostic accuracy 95.2%, positive predictive value 100%, negative predictive value 92.6%. Thallium exercise myocardial scintigraphy: positive in 30 cases (71.4%), negative in 12 (28.6%); sensitivity 100%, specificity 48%, diagnostic accuracy 69%, positive predictive value 56.7%, negative predictive value 100%. CONCLUSIONS: Dipyridamole-echocardiography test has higher diagnostic accuracy and when positive, it predicts significant epicardial coronary stenosis. It can be less sensitive in one-vessel patients (2 false negatives were stenosis 75% of left anterior descending and 60% of 1st diagonal). Thallium exercise myocardial scintigraphy is complementary because when negative, it excludes epicardial coronary stenosis and confirms microvascular disease. In hypertensive patients with left ventricular hypertrophy and suspected angina pectoris, the following flow-chart may be proposed: the first test is exercise-electrocardiography test. Only those who are positive at low-to-intermediate workload then undergo dipyridamole-echocardiography test. Those who are positive in this then undergo coronarography, while the negative ones undergo thallium exercise myocardial scintigraphy. Those who are positive at thallium exercise myocardial scintigraphy perform the coronarography, while cases with negative results do not undergo further diagnostic tests since they are affected with microvascular disease.

[Carcinogens in the urban environment of Italian cities: benzene and benzo(a)pyrenes]. / Cancerogeni nell'ambiente urbano delle città italiane: benzene e benzo(a)pirene.

In Italian urban areas air pollution from benzene and benzo(a)pyrene-B(a)P--is mostly caused by traffic. The concentration limits in the atmosphere fixed by Italian legislation up to December 31, 1998 expressed as annual means are 15 micrograms/m3 and 2.5 ng/m3 for benzene and B(a)P respectively and, starting from January 1, 1999, 10 micrograms/m3 and 1 ng/m3. In the city of Florence the concentrations detected and expressed as annual means of benzene and B(a)P in an area with heavy traffic (32.1 micrograms/m3 and 3.5 ng/m3), in a densely populated area (9.2 micrograms/m3 and 1.86 ng/m3), and in a city park (6.0 micrograms/m3 and 0.25 ng/m3), suggest a marked progressive reduction in the atmospheric levels of these chemicals with the distance from the main roads. The environmental data obtained from densely populated areas of a number of Italian cities (Firenze, Milano, Roma, Bologna, Bolzano, Pavia, Modena), the only ones that allow evaluation of the health risk, show benzene concentrations ranging from 6.0 to 11.3 micrograms/m3 and B(a)P levels, measured in heavy traffic areas, from 1.0 to 3.5 ng/m3 respectively (annual mean in 1996). The data obtained in the city of Florence show that the population is exposed weekly to average concentrations of 14.3 micrograms/m3 for benzene and 2.0 ng/m3 for B(a)P. These results suggest that, regarding benzene and B(a)P pollution, the situation in Florence is far from being critical but not such as to ensure that long-term exposure is without adverse effects.