Anomalous Coronary Artery Origin in a Young Patient with Marfan Syndrome.

Marfan syndrome is an autosomal dominant genetic disorder that affects connective tissue and is caused by mutations in the fibrillin 1 gene present at chromosome 15. Aortic aneurysm is its main complication, and along the dilation of the aorta root and its descending portion (60-100%), with secondary aortic insufficiency, it increases risk of acute aortic dissection and death. Coronary artery anomalies affect between 0.3% and 1.6% of the general population and are the second leading cause of sudden death in young adults, especially if the anomalous coronary passes through aorta and pulmonary artery. The anomalous origin of the left main coronary artery in the right Valsalva sinus has a prevalence of 0.02%-0.05% and is commonly related to other congenital cardiac anomalies, such as transposition of great vessels, coronary fistulas, bicuspid aortic valve, and tetralogy of Fallot. Its association with Marfan syndrome is not known, and there is no previous report in the literature. We describe here a case of a female with Marfan syndrome diagnosed with symptomatic anomalous origin of the left coronary artery in the right Valsalva sinus.

The metabolic treatment of patients with coronary artery disease: effects on quality of life and effort angina.

The effectiveness of drug therapy in controlling angina and the resulting improvement in exercise capacity were reviewed. We performed a Medline search of published reports on ranolazine, trimetazidine, and other medicines that act metabolically. Quality of life with regards to work capacity alone was analyzed. Most reports were about trimetazidine, with strong evidence of its efficacy and tolerability. Its effect on episodes of angina, total exercise time, and time to the onset of ischemia on ECG is impressive with no negative effects found on double product (workload) and improvement in quality of life. The second most evaluated drug was ranolazine, particularly regarding quality of life. Results are similar to those with trimetazidine but are not as significant for quality of life issues. For the other drugs, L-carnitine, ribose, and dichloroacetate, accumulated experimental data provide a physiological background in which clinical trials have been started, but as yet very few patients have been enrolled. Also, studies that intended to evaluate, by echocardiography, ischemic dysfunction induced by dobutamine-atropine stress were examined; these also showed a reduction in ischemia and fewer anginal episodes, but only with trimetazidine in this regard. Taken together, these drug effects are important to ameliorate quality of life. The issue of quality of life was evaluated in specific reports, and the results of the application of validated questionnaires (SF36, 5-dimensional EuroQol Instrument, and Seattle Angina Questionnaire) attest to the positive drug effects on patients' perception of wellness, particularly with the use of trimetazidine, and less with ranolazine.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil.

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6 degrees C. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4% (relative risk of 1.03; 95% confidence interval = 1.02-1.05) for each 10 microg/m(3) increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6ºC. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4 percent (relative risk of 1.03; 95 percent confidence interval = 1.02-1.05) for each 10 µg/m increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

Morphological and biochemical changes of pituitary gonadotropes in male golden hamsters submitted to short and long photoperiods.

Golden hamsters are seasonal breeders, and a pattern of regression-recrudescence in their hypothalamic-pituitary axis is observed when adult animals are exposed to less than 12.5 h daylight for a prolonged period of time. The purpose of the present work was to investigate the possible morphological and biochemical changes of gonadotrope cell population in male golden hamsters submitted to both short (SP) and long photoperiods (LP). Thus, adult male golden hamsters were exposed to SP (6 h light, 18 h darkness) for 8, 16, 22 and 28 weeks or maintained under LP (14 h light, 10 h darkness). Pituitaries were processed using both light and electron microscopy, and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were assessed by heterologous radioimmunoassay. Volume density [VD = Sigma cell area/reference area (RA)] and cell density (CD = number of cells/RA) of gonadotropes were measured with an image analysis system (Imaging Technology, Software Optimas 5.2). When analyzing the gonadotrope population from animals submitted either to SP or LP, no significant differences were found. At the ultrastructural level, we found a decrease (p < 0.05) in the exocytotic profiles and the individual mean area of secretory granules of both gonadotropes in hamsters maintained under SP for 16 and 22 weeks. Exposure to short days resulted in a decline in serum levels showing a nadir after 16 weeks (p < 0.05). Gonadotropin levels of the hamsters under prolonged exposure to short cycles spontaneously returned to normal values after 22 weeks. In summary, we found a decrease in the ultrastructural and biochemical parameters suggesting an altered release of FSH and LH in male golden hamsters submitted to SP, with a spontaneous recrudescence phase appearing at the end of the study.

Influence of photoinhibition on the morphology and function of pituitary lactotropes in male golden hamsters.

Inhibition of prolactin (PRL) secretion has been previously shown in pituitaries from male and female hamsters exposed to short photoperiods. The purpose of the present study was to analyze the possible quantitative immunohistochemical and ultrastructural changes of PRL cells in male golden hamsters undergoing regression and spontaneous recrudescence, correlating the morphological findings with circulating PRL levels. Thus, adult male golden hamsters were exposed for 8, 16, 22 and 28 weeks to either short photoperiods (SP: 6 h light, 18 h darkness) or long photoperiods (LP: 14 h light, 10 h darkness). Pituitaries were processed for both light and electron microscopy, and serum levels of PRL were assessed by radioimmunoassay (RIA). Volume density (VD = cell area/reference area) and cell density (CD = number of cells/reference area) of lactotropes were measured with an image analysis system (Imaging Technology, Software Optimas 5.2). One hundred lactotropes were recorded for measuring several ultrastructural parameters. When analyzing the lactrotrope cell population from animals submitted to SP, the VD and CD were found to be significantly (p < 0.05) diminished with respect to those of the groups submitted to LP at weeks 8, 16 and 22. However, at week 28 a spontaneous recrudescence appeared. The lactotropes from animals submitted to LP for 8, 16, 22 and 28 weeks exhibited numerous large electrondense secretory granules. The rough endoplasmic reticulum (RER) presented some flat cisternae and numerous free ribosomes. Animals submitted to SP for 8 weeks showed a number of medium and large secretory granules, and the RER exhibited mainly numerous free ribosomes. In those animals submitted to SP for 16 and 22 weeks, lactotropes were found smaller and showed small and medium-sized secretory granules decreased in number. The Golgi complex exhibited some immature granules and dilated cisternae, while the RER did not present differences with respect to the 8-week SP group. The hamsters submitted to SP for 28 weeks presented medium and large secretory granules, and the RER exhibited dilated irregular cisternae. The ultrastructural morphometric parameters showed a decrease (p < 0.05) in the number of secretory granules and exocytotic profiles, as well as a diminution (p < 0.05) in the areas of Golgi complex, RER, secretory granules, and individual mean area of secretory granule during the 16 and 22 weeks of SP. Serum PRL levels were severely reduced under SP. This decrease was greater at 16 weeks than at 8 weeks of exposure. When hamsters were kept for 22 weeks under SP, PRL levels started their recovery. Thus, at the end of the experiment, the PRL values returned to near those of LP group. In summary, we found quantitative immunohistochemical and ultrastructural, as well as biochemical changes that suggest an inhibition of synthesis, storage and release of PRL in male golden hamsters submitted to SP, with a spontaneous recrudescence appearing at the end of the study.

Clustering of traditional risk factors and precocity of coronary disease in women.

BACKGROUND: Women usually develop coronary artery disease (CAD) 10 years later than men do. CAD in women is associated with menopausal status and the number and intensity of risk factors. But, when the age gap between men and women narrows, less is known about the influence of risk factors on CAD. METHODS: We assessed the prevalence of traditional risk factors in 850 men and 468 women with stable CAD who had mean age, 58.3+/-8.6 and 58.8+/-10.3 years (P=NS), respectively. RESULTS: Univariate analysis of risk factors showed that body mass index (BMI), hypertension (all three stages), diabetes, triglycerides (> or =2.8 mmol/l), cholesterol (> or =6.2 mmol/l) and family history were more prevalent in women. Smoking and previous myocardial infarction (MI) were more prevalent in men. Multivariable analysis disclosed hypertension, diabetes, dyslipidemia and family history as independent risk factors for women with stable CAD and smoking and previous MI as independent risk factors for men. CONCLUSION: Clustering of traditional risk factors may explain the precocity of CAD in women who are near in age to men.

Cholesterol lowering with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with coronary artery disease.

Coronary flow reserve is mainly influenced by the combination of luminal stenosis and vascular dilation capacity. Thus, after statin treatment, the reduction of ischemic threshold in patients submitted to exercise testing could be intensely influenced by angiographic severity. In this study, we verify the effect of statin treatment on exercise-induced myocardial ischemia in hypercholesterolemic patients with a broad range of coronary angiographic severities. Patients with 2 consecutive positive exercise tests, coronary stenosis > or =70%, total cholesterol > or =300 mg/dl, and triglycerides < or =200 mg/dl were randomly assigned to a 16-week treatment period with either diet alone (n = 39) or diet plus statins (simavastatin, n = 31 and pravastatin, n = 10). Statin-treated patients had a significant variation in total cholesterol (-46% vs -2.7%; p <0.01), low-density lipoprotein cholesterol (-58% vs 0.8%; p <0.01), and high-density cholesterol (+28% vs -6%; p <0.05) in comparison with the diet-only group. After 16 weeks of treatment, 36 patients (92%) in the diet group still had positive exercise tests, whereas only 7 patients (15%) of the statin group had a positive test (p <0.01). The proportion of positive tests was significantly reduced in subgroups of patients with 1-, 2-, or 3-vessel disease. Regarding the severity of coronary stenosis, the proportion of positive tests was significantly reduced in patients with stenosis between 70% and 90% and in patients with stenosis > or =90%. Moreover, the proportion of positive tests tended to decrease to a greater extent in patients with mild coronary disease. In conclusion, cholesterol-lowering treatment with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with mild or severe epicardial coronary stenosis.

Trends in death from circulatory diseases in Brazil between 1979 and 1996.

OBJECTIVE: To analyze the trends in mortality due to circulatory diseases in men and women aged > or =30 years in Brazil from 1979 to 1996. METHODS: We analyzed population count data obtained from the IBGE Foundation and mortality data obtained from the System of Information on Mortality of the DATASUS of the Ministry of Health. RESULTS: Circulatory diseases, ischemic heart disease, and cerebrovascular disease were the major causes of death in men and women in Brazil. The standardized age coefficient for circulatory disease in men aged > or =30 years ranged from 620 to 506 deaths/100,000 inhabitants and in women from 483 to 383 deaths/100,000 inhabitants for the years 1979 and 1996, respectively. In men, the mean coefficient for the period was 586.25 deaths with a significant trend towards a decrease (P<0.001) and a decline of 8.25 deaths/year. In women, the mean coefficient for the period was 439.58 deaths, a significant trend towards a decrease (P<0.001) and a rate of decline of 7.53 deaths/year. The same significant trend towards a decrease in death (P<0.001) was observed for ischemic heart disease and cerebrovascular disease. Risk of death from these causes was always higher for men of any age group (P<0.001). Cerebrovascular disease was the primary cause of death in women. CONCLUSION: Although circulatory diseases have been the major cause of mortality in men and women in the Brazilian population, with a greater participation by cerebrovascular diseases, a trend towards a decrease in the risk of death from these causes is being observed.

Does a circadian variation occur in myocardial ischemia over 48 hours in patients with unstable angina?

OBJECTIVE: To study the incidence of and variation in myocardial ischemia over 48 hours in patients with unstable angina. METHODS: Thirty-nine patients with unstable angina underwent long-term electrocardiography for 48 hours. The number of events and the period of time of ischemia (in minutes) were analyzed for the 48 hours, in two periods of 24 hours, and in periods of 4 hours. RESULTS: We analyzed 1755.8 hours of monitoring tapes, and ischemic episodes were detected in 18 (46.2%) patients, corresponding to 173 ischemic episodes, allowing the evaluation of 1304 minutes of ischemia.only 4 of which were (2.2%) symptomatic, Considering the entire period of time of recording and the predetermined time intervals, we observed a higher number of ischemic episodes (38) and a longer duration of ischemia (315.4 minutes) between 11:00 am and 3:00 pm. However, no significant differences occurred among the values in the different intervals. CONCLUSION: Long-term electrocardiography over 48 hours showed a high incidence (97.8%) of silent ischemic episodes in patients with unstable angina. No evidence of a circadian variation of myocardial ischemia in unstable angina was observed.

Angiotensin-converting enzyme and apolipoproteins genes polymorphism in coronary artery disease.

BACKGROUND: Association between angiotensin-converting enzyme (ACE) as well as apolipoprotein (apo) AI, B, and E polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. HYPOTHESIS: This study assessed the distribution of ACE insertion/deletion, apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length, and apo E polymorphisms in 388 nondiabetic patients. METHODS: The study population included 112 patients with stable CAD, 139 patients with acute myocardial infarction (AMI), and 137 age-matched control subjects. RESULTS: Univariate analysis showed higher prevalence of XbaI X+/X+ genotype in patients with CAD (p = 0.02). Angiotensin-converting enzyme and apo polymorphisms were not associated with lipid levels or severity of CAD. When all genotypes known to be related to CAD; such as ACE DD, apo AI GG, apo B del/del, and XbaI X+X+, and E4 allele of apo E, were pooled, again no significant differences among groups were seen. Multivariate regression analysis disclosed traditional risk factors and elevated levels of apo B for men and reduced levels of apo AI for women as independent variables for CAD. CONCLUSIONS: In addition to traditional coronary risk factors, apo B and AI could be considered predictors of CAD. No association between either form of CAD and polymorphisms was noted.

Effect of pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease.

The speed of the plasma removal of chylomicrons, the lipoproteins that carry dietary lipids absorbed in the intestine, may influence atherogenesis. Thus, the effects of a 30-day pravastatin or placebo treatment on the plasma kinetics of chylomicron-like emulsions were evaluated in 25 patients with coronary artery disease who were not hypertriglyceridemic in a randomized, single-blinded study. Eleven patients (53 +/- 4 years, 10 men) received pravastatin 40 mg/day and 14 received placebo (52 +/- 3 years, 13 men). Emulsions labeled with triolein ((3)H-TO) and cholesteryl oleate ((14)C-CO) to assess lipolysis and clearance of chylomicron and remnants, respectively, were injected intravenously in a bolus after a 12-hour fast. Blood samples were collected during 60 minutes to determine radio isotope decaying curves and fractional catabolic rates. Subjects were studied at baseline and after the treatment period. Compared with placebo (data expressed as mean +/- SEM), pravastatin treatment increased the (14)C-CO fractional catabolic rates (70 +/- 45% vs 18 +/- 10%, p = 0.01), reduced total cholesterol (-21 +/- 3% vs -3 +/- 2% p = 0.0001), low-density lipoprotein (LDL) cholesterol (-25 +/- 5% vs 4 +/- 6%, p = 0.0001), and apolipoprotein B levels (-22 +/- 3% vs -7 +/- 3% p = 0.01). (3)H-TO fractional catabolic rates, plasma triglycerides, very-low-density lipoprotein (VLDL) cholesterol and high-density lipoprotein (HDL) cholesterol variations did not differ between the groups. The fractional catabolic rate of (14)C-CO was inversely correlated with plasma apolipoprotein B levels (r = -0.7, p = 0.04). This suggests that besides reducing LDL cholesterol, pravastatin also increases chylomicron remnant clearance, with possible antiatherogenic implications.

Angiotensin-converting enzyme and apolipoprotein B polymorphisms in coronary artery disease.

The association between angiotensin-converting enzyme (ACE) as well as apolipoprotein B polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. We assessed the distribution of ACE insertion and/or deletion, apolipoprotein B signal peptide insertion and/or deletion, and apolipoprotein B XbaI restriction fragment length polymorphisms in 388 nondiabetic patients. We studied 112 patients with angiographically defined asymptomatic CAD or with stable functional classes I and II angina and 139 patients with acute myocardial infarction who were age matched to 137 control subjects. Univariate analysis showed higher prevalence of Xba50% reduction of lumen diameter. Overall, multivariable regression disclosed traditional risk factors and elevated levels of apolipoprotein B for men and reduced levels of apolipoprotein AI for women as independent variables for CAD. After adjustment for the most important subset of risk factors (age, hypertension, hypercholesterolemia, and smoking), apolipoprotein B XbaI polymorphism was disclosed as an independent variable for CAD. Apolipoprotein B XbaI was also selected as an independent variable for acute myocardial infarction after adjusting for age, hypertension, hypercholesterolemia, and smoking. Thus, in addition to traditional coronary risk factors, apolipoproteins B and AI, and apolipoprotein B XbaI polymorphism could be considered predictors of CAD.

Quantitative ultrastructural changes induced by sucrose administration in the pancreatic B cells of normal hamsters

We have previously reported that young male Syrian hamsters receiving a sucrose-rich diet presented increased B-cell replication rate and size. The aim of the present study was to analyze, under the same experimental conditions, the ultrastructural changes in B cells. For this purpose, young male Syrian hamsters were fed with a commercial diet and 10 sucrose in their drinking water (S group) while the control group (C) received the same diet and tap water, for 5 weeks. Samples of the pancreas removed after that period were processed for the immunohistochemical identification of B cells as well as for measuring several ultrastructural parameters. S hamsters showed higher serum insulin levels, while similar serum glucose values were obtained in animals from both groups. The B cells from S group exhibited lesser number of dense secretory granules at expenses of an increase of the pale ones, increased number of both exocytosis profiles and fusion-granule images, as well as enlargement of the intercellular space and mitochondrial area. Marked expansions of this space, limited by junctional complexes, were observed between adjacent B cells. These results would indicate that sucrose administration to normal hamsters not only increases the pancreatic B-cell mass but also induces measurable subcellular changes in the individual B-cell characteristic of an enhanced secretory activity. The present model would represent a useful tool for testing strategies in preventing the damage or promoting the recovery of the pancreatic B cells.

Quantitative ultrastructural changes induced by sucrose administration in the pancreatic B cells of normal hamsters

We have previously reported that young male Syrian hamsters receiving a sucrose-rich diet presented increased B-cell replication rate and size. The aim of the present study was to analyze, under the same experimental conditions, the ultrastructural changes in B cells. For this purpose, young male Syrian hamsters were fed with a commercial diet and 10 sucrose in their drinking water (S group) while the control group (C) received the same diet and tap water, for 5 weeks. Samples of the pancreas removed after that period were processed for the immunohistochemical identification of B cells as well as for measuring several ultrastructural parameters. S hamsters showed higher serum insulin levels, while similar serum glucose values were obtained in animals from both groups. The B cells from S group exhibited lesser number of dense secretory granules at expenses of an increase of the pale ones, increased number of both exocytosis profiles and fusion-granule images, as well as enlargement of the intercellular space and mitochondrial area. Marked expansions of this space, limited by junctional complexes, were observed between adjacent B cells. These results would indicate that sucrose administration to normal hamsters not only increases the pancreatic B-cell mass but also induces measurable subcellular changes in the individual B-cell characteristic of an enhanced secretory activity. The present model would represent a useful tool for testing strategies in preventing the damage or promoting the recovery of the pancreatic B cells.(AU)

Five-year follow-op of the medicine, angioplasty, or surgery study (MASS): A prospective, randomized trial of medical therapy, balloon angioplasty, or bypass surgery for single proximal left anterior descending coronary artery stenosis.

BACKGROUND: Although coronary angioplasty and myocardial bypass surgery are routinely used, there is no conclusive evidence that these interventional methods offer greater benefit than medical therapy alone. This study is intended to evaluate, in a prospective, randomized, and comparative analysis, the benefit of the 3 current therapeutic strategies for patients with stable angina and single proximal left anterior descending coronary artery stenosis. METHODS AND RESULTS: In a single institution, 214 patients with stable angina, normal ventricular function, and severe proximal stenosis (>80%) on the left anterior descending artery were selected for the study. After random assignment, 70 patients were referred to surgical treatment, 72 to angioplasty, and 72 to medical treatment. The primary end points were the occurrence of acute myocardial infarction or death and presence of refractory angina. After a 5-year follow-up, these combined events were reported in only 6 patients referred to surgery as compared with 29 patients treated with angioplasty and 17 patients who only received medical treatment (P=0.001). However, no differences were noted in relation to the occurrence of cardiac-related death in the 3 treatment groups (P=0. 622). No patient assigned to surgery needed repeat operation, whereas 8 patients assigned to angioplasty and 8 patients assigned to medical treatment required surgical bypass after the initial random assignment. Surgery and angioplasty reduced anginal symptoms and stress-induced ischemia considerably. However, all 3 treatments effectively improved limiting angina. CONCLUSIONS: Bypass surgery for single-vessel coronary artery disease is associated with a lower incidence of medium-term and long-term events as well as fewer anginal symptoms than that found in the patients who underwent angioplasty or medical therapy. In this study, coronary angioplasty was only superior to medical strategies in relation to the anginal status. However, the 3 treatment regimens yielded a similar incidence of acute myocardial infarction and death. Such information should be useful when choosing the best therapeutic option for similar patients.