The lack of knowledge on acute stroke in Brazil: A cross-sectional study with children, adolescents, and adults from public schools.

OBJECTIVE: Stroke is an important cause of disability and death in adults worldwide. However, it is preventable in most cases and treatable as long as patients recognize it and reach capable medical facilities in time. This community-based study investigated students' stroke knowledge, Emergency Medical Services (EMS) activation, associated risk factors, warning signs and symptoms, and prior experience from different educational levels in the KIDS SAVE LIVES BRAZIL project. METHODS: The authors conducted the survey with a structured questionnaire in 2019‒2020. RESULTS: Students from the elementary-school (n = 1187, ∼13 y.o., prior experience: 14%, 51% women), high-school (n = 806, ∼17 y.o., prior experience: 13%, 47% women) and University (n = 1961, ∼22 y.o., prior experience: 9%, 66% women) completed the survey. Among the students, the awareness of stroke general knowledge, associated risk factors, and warning signs and symptoms varied between 42%‒66%. When stimulated, less than 52% of the students associated stroke with hypercholesterolemia, smoking, diabetes, and hypertension. When stimulated, 62%‒65% of students recognized arm weakness, facial drooping, and speech difficulty; only fewer identified acute headache (43%). Interestingly, 67% knew the EMS number; 81% wanted to have stroke education at school, and ∼75% wanted it mandatory. Women, higher education, and prior experience were associated with higher scores of knowing risk factors (OR = 1.28, 95% CI: 1.10‒1.48; OR = 2.12, 95% CI: 1.87‒2.40; OR = 1.46, 95% CI: 1.16‒1.83; respectively), and warning signs- symptoms (OR = 2.22, 95% CI: 1.89‒2.60; OR = 3.30, 95% CI: 2.81‒3.87; OR = 2.04, 95% CI: 1.58‒2.63; respectively). CONCLUSION: Having higher education, prior experience, and being a woman increases stroke-associated risk factors, and warning signs and symptoms identification. Schoolchildren and adolescents should be the main target population for stroke awareness.

CPR Quality Assessment in Schoolchildren Training.

Whilst CPR training is widely recommended, quality of performance is infrequently explored. We evaluated whether a checklist can be an adequate tool for chest compression quality assessment in schoolchildren, compared with a real-time software. This observational study (March 2019-2020) included 104 schoolchildren with no previous CPR training (11-17 years old, 66 girls, 84 primary schoolchildren, 20 high schoolchildren). Simultaneous evaluations of CPR quality were performed using an observational checklist and real-time software. High-quality CPR was determined as a combination of 70% correct maneuvers in compression rate (100-120/min), depth (5-6 cm), and complete release, using a real-time software and three positive performance in skills using a checklist. We adjusted a multivariate logistic regression model for age, sex, and BMI. We found moderate to high agreement percentages in quality of CPR performance (rate: 68.3%, depth: 79.8%, and complete release: 91.3%) between a checklist and real-time software. Only 38.5% of schoolchildren (~14 years-old, ~54.4 kg, and ~22.1 kg/m2) showed high-quality CPR. High-quality CPR was more often performed by older schoolchildren (OR = 1.43, 95%IC:1.09-1.86), and sex was not an independent factor (OR = 1.26, 95%IC:0.52-3.07). For high-quality CPR in schoolchildren, a checklist showed moderate to high agreement with real-time software. Better performance was associated with age regardless of sex and BMI.

Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats.

BACKGROUND: Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes. METHODS: Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. RESULTS: In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. CONCLUSION: Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

Biochemical markers of muscle damage and high serum concentration of creatine kinase in patients on statin therapy.

Aim: Some patients experience statin-associated muscle symptoms (SAMS) and elevated serum concentrations of CK. The relationship between SAMS and biomarkers of muscle damage was examined. Methods: We analyzed 359 consecutive patients taking statins with high CK values. Muscle-related symptoms and biochemical variables, including CK, MB isoenzyme of creatine kinase (CK-MB), troponin and carbonic anhydrase type III were evaluated. Results: SAMS was reported by 181 (50.4%) patients and they had greater BMI (p = 0.021) and a trend toward higher CK-MB values (p = 0.064). The use of simvastatin (OR: 2.24; 95% CI: 1.47-3.42), CK-MB (OR: 1.59; 95% CI: 1.02-2.49) and BMI (OR: 1.06; 95% CI: 1.01-1.10) were independent variables for SAMS. Conclusion: Simvastatin use, BMI and CK-MB were independent markers of SAMS.

Cerebral blood flow changes during intermittent acute hypoxia in patients with heart failure.

Objective Heart failure (HF) is associated with intermittent hypoxia, and the effects of this hypoxia on the cardiovascular system are not well understood. This study was performed to compare the effects of acute hypoxia (10% oxygen) between patients with and without HF. Methods Fourteen patients with chronic HF and 17 matched control subjects were enrolled. Carotid artery changes were examined during the first period of hypoxia, and brachial artery changes were examined during the second period of hypoxia. Data were collected at baseline and after 2 and 4 minutes of hypoxia. Norepinephrine, epinephrine, dopamine, and renin were measured at baseline and after 4 minutes hypoxia. Results The carotid blood flow, carotid systolic diameter, and carotid diastolic diameter increased and the carotid resistance decreased in patients with HF. Hypoxia did not change the carotid compliance, distensibility, brachial artery blood flow and diameter, or concentrations of sympathomimetic amines in patients with HF, but hypoxia increased the norepinephrine level in the control group. Hypoxia increased minute ventilation and decreased the oxygen saturation and end-tidal carbon dioxide concentration in both groups. Conclusion Hypoxia-induced changes in the carotid artery suggest an intensification of compensatory mechanisms for preservation of cerebral blood flow in patients with HF.

Effects of carvedilol treatment in dogs with chronic mitral valvular disease.

BACKGROUND: Stimulation of the sympathetic nervous system occurs during the development of heart failure in dogs with chronic mitral valvular disease (CMVD). HYPOTHESIS: The use of beta-blockers to modulate the activation of the sympathetic nervous system would be useful in dogs with CMVD. ANIMALS: Group A included 13 dogs who received the conventional treatment (digoxin, benazepril, a reduced sodium diet, and codeine, and a diuretic when indicated), and group B included 12 dogs who received the protocol above plus carvedilol (0.3 mg/kg q12h). METHODS: Blinded, placebo, controlled study. RESULTS: The main echodopplercardiographic variables, heart rate, biochemical data, functional classification (FC) (New York Heart Association) and quality of life score (functional evaluation of cardiac health questionnaire) were assessed at baseline (TO) and after 3 months (T1). Only group B showed improvement in score of quality of life (13.8 +/- 8.8 versus 6.0 +/- 6.3; P < .001), in FC (2.4 - 0.9 versus 1.8 +/- 0.7; P = .032) and a reduction in systolic blood pressure (151.2 +/- 18.3 versus 124.5 +/- 23.4; P = .021). Two deaths from group A and 1 from B were related to CMVD. CONCLUSION: The studied dose of carvedilol in this group did not improve the sympathetic activation and echocardiographic variables over 3 months of chronic oral treatment. However, the results suggested a beneficial effect on the quality of life score, functional classification, and a reduction on systolic blood pressure.

Elective vs non-elective radial artery grafts: comparing midterm results through 64-Slice computed tomography.

BACKGROUND: Left internal thoracic artery to left anterior descending artery (LITA-LADA) grafting has become a fundamental part of the coronary artery bypass graft procedure (CABG). This grafting in turn has led to an increased use of other arterial conduits, of which the radial artery (RA) is most popular. Whether RA grafting can be used in the emergency patient is controversial. METHODS: 47 patients with critical stenosis (>70%) in all target vessels underwent CABG with LITA and RA grafts from 1996 to 2003. Patients were divided into elective (23 patients) and non-elective groups (24 patients) with LITA and RA grafts per patient being similar in both groups. Of these 47 patients, 5 died from non-cardiac complications and 12 were unavailable. Thus, 30 patients (71% of survivors) were studied by multidetector computed tomography. A total of 36 LITA and 64 RA grafts were studied. RESULTS: The RA patency rate for elective and non-elective grafts were 82% (31/38) and 85% (22/26), respectively (p=0.75). The RA had a similar patency rate for all target vessels ranging from 73% to 100%. Only one patient had a redo CABG and 29 (97%) are free from angina or re-intervention. LITA-LADA had a 92% (11/12) and 100% (10/10) patency rate for elective and non-elective groups, respectively (p=0.37). The sequential LITA-diagonal-LADA in the elective group had a 50% (03/06) patency rate, which was significantly lower than the 100% (08/08) patency rate of the non-elective group (p=0.02). CONCLUSION: Radial Artery grafts can be used in both elective and non-elective patients with excellent results.

Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial.

BACKGROUND: Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population. METHODS AND RESULTS: Forty-eight healthy participants (24 women) aged 55-65years were randomized to either 30days of resveratrol administration (500mg/day) or caloric restriction (1000cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06±0.71 to 5.75±2.98ng/mL; p<0.0001, and from 1.65±1.81 to 5.80±2.23ng/mL; p<0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment. CONCLUSIONS: Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long-term impact of these interventions on atherosclerosis should be assessed.

The lack of knowledge on acute stroke in Brazil: A cross-sectional study with children, adolescents, and adults from public schools

Abstract Objective: Stroke is an important cause of disability and death in adults worldwide. However, it is preventable in most cases and treatable as long as patients recognize it and reach capable medical facilities in time. This community-based study investigated students' stroke knowledge, Emergency Medical Services (EMS) activation, associated risk factors, warning signs and symptoms, and prior experience from different educational levels in the KIDS SAVE LIVES BRAZIL project. Methods: The authors conducted the survey with a structured questionnaire in 2019‒2020. Results: Students from the elementary-school (n = 1187, ~13 y.o., prior experience: 14%, 51% women), high-school (n = 806, ~17 y.o., prior experience: 13%, 47% women) and University (n = 1961, ~22 y.o., prior experience: 9%, 66% women) completed the survey. Among the students, the awareness of stroke general knowledge, associated risk factors, and warning signs and symptoms varied between 42%‒66%. When stimulated, less than 52% of the students associated stroke with hypercholesterolemia, smoking, diabetes, and hypertension. When stimulated, 62%‒65% of students recognized arm weakness, facial drooping, and speech difficulty; only fewer identified acute headache (43%). Interestingly, 67% knew the EMS number; 81% wanted to have stroke education at school, and ~75% wanted it mandatory. Women, higher education, and prior experience were associated with higher scores of knowing risk factors (OR = 1.28, 95% CI: 1.10‒1.48; OR = 2.12, 95% CI: 1.87‒2.40; OR = 1.46, 95% CI: 1.16‒1.83; respectively), and warning signs- symptoms (OR = 2.22, 95% CI: 1.89‒2.60; OR = 3.30, 95% CI: 2.81‒3.87; OR = 2.04, 95% CI: 1.58‒2.63; respectively). Conclusion: Having higher education, prior experience, and being a woman increases stroke-associated risk factors, and warning signs and symptoms identification. Schoolchildren and adolescents should be the main target population for stroke awareness. HIGHLIGHTS Higher education, prior experience, and being women improved the odds of identifying stroke warning signs and symptoms as associated risk factors Improving knowledge, skills, and attitude on acute stroke in the school community may represent a significant advance in public health management Future stroke awareness campaigns and educational efforts should focus on schoolchildren and adolescents, especially in low-income countries

Platelet glycoprotein Ibalpha polymorphisms modulate the risk for myocardial infarction.

Platelet glycoprotein Iba (GPIba) gene polymorphisms have been reported to affect the risk of developing coronary heart disease. Here, within the GPIba gene, we determine the association between the variable number of tandem repeats (VNTR), the -5C/T Kozak sequence dimorphism, and the human platelet antigen (HPA)-2 polymorphisms with occurrence of myocardial infarction (MI). Patients (n=180) presenting survivors of MI were compared to 180 controls matched by age, gender, and race. Carriers of VNTR-CD genotype had a 2-fold higher risk for MI compared to controls. The prevalence of VNTR-BC was lower among patients than among controls (P=.007). These data are in agreement with recent reports of increased plug formation by human platelets containing VNTRCD but no other VNTR genotypes. Among patients, the number of vessels severely occluded was greater among carriers of the D-allele (P=.019) or VNTR-CD (P=.026) and lower among carriers of the C-allele (P=.003) or VNTR-CC (P=.0009) compared to non-carriers of these alleles. No influence was seen with the Kozak or HPA-2 polymorphisms. Determination of VNTR of the GPIba gene may prove useful for identifying high-risk individuals for MI.

PON1 M/L55 mutation protects high-risk patients against coronary artery disease.

The paraoxonase (PON) gene family contains at least three members: PON1, PON2, and PON3. The enzyme PON1 has been implicated in the pathogenesis of atherosclerosis. Recently, an association between PON2 and quantitative metabolic phenotypes, such as plasma lipoproteins, plasma glucose, and coronary artery disease (CAD), has been reported. We analyzed two common polymorphisms in PON1 (i.e., M/L55 and R/Q 192 mutations) and PON2 (i.e., G/A148 and C/S311 mutations) in 352 high-risk patients with angiographically defined CAD. These results were compared to those in 380 age- and sex-matched control subjects at high risk for CAD. Polymerase chain reaction with specific primers followed by Hsp92, Alw1, DdeI and Fnu4HI restriction digestion were employed to identify the PON1 M/L55 and R/Q192 and the PON2 G/A148 and C/S311 genotypes, respectively. Univariate analysis showed a higher prevalence of the MM genotype (12% vs. 5%; p=0.004) for the PON1 M/L55 polymorphism and the GG genotype (21% vs. 15%; p=0.047) PON2 G/A148 polymorphism in the control subjects. The PON1 M/L55 mutation (MM genotype) was associated with lower triglyceride levels and the PON2 G/A148 mutation (GG genotype), with higher total and low-density lipoprotein (LDL)-cholesterol levels. No mutation was associated with the number of major coronary artery vessels with a >50% reduction in lumen diameter. Multiple regression analysis disclosed smoking, a family history of CAD, high-density lipoprotein (HDL)-cholesterol and the PON1 M/L55 mutation [OR=0.59 (CI95%: 0.42-0.82); p=0.002] as independent markers for CAD. In contrast to traditional coronary risk factors, the PON1 M/L mutation can be considered predictive of protection against CAD.

The pre-existence of an acute coronary event predicts differences in biological parameters and clinical evolution among patients with longstanding stable angina.

BACKGROUND: To date, patients displaying stable angina with or without a previous acute coronary event have been grouped together and are offered nowadays, similar clinical approach. However, from clinical experience, increasing doubt exists whether they behave clinically in the same way. In the current study, we investigated whether differences might exist in the clinical, angiographic and biological parameters between these two distinct clinical presentations. METHODS: The cardiovascular risk factor profile, clinical evolution, angiographic data, white blood cell (WBC) count and plasma concentrations of lipids and fibrinogen were compared between two groups of patients with longstanding stable angina. The first group consisted of 160 subjects who had undergone myocardial infarction (MI) as the first manifestation of coronary artery disease (CAD) and had no further coronary event. The second group was composed of 226 subjects who had effort-induced angina but never experienced an acute coronary event. The mean period between the first CAD manifestation and entry into the study was 7+/-6 years for MI group and 7+/-4 years for patients with uneventful angina. RESULTS: MI patients displayed 8% higher WBC count (P=0.038), 20% higher fibrinogen (P=0.001), 12% lower HDL cholesterol (P=0.02), 8% lower apoA1 (P=0.005) and 46% higher lipoprotein (a) (P=0.005) than patients who presented an uneventful clinical course. Upon multivariate logistic regression analysis, fibrinogen (OR=1.14; 95% CI=1.08-1.28; P=0.033), lipoprotein (a) (OR=1.19; 95% CI=1.05-1.34; P=0.0036) and HDL cholesterol levels (OR=0.97; 95% CI=0.94-0.99; P=0.0095) remained independently associated with the pre-existence of MI. Patients with prior MI evolved more frequently towards clinically refractory angina (P=0.04). In addition, fibrinogen levels were independently associated with evolution to clinically refractory angina (OR=1.03; 95% CI=1.005-1.550; P=0.0448). CONCLUSIONS: Stable CAD patients with a prior MI differ from those who display an uneventful effort-induced angina in their biological profile and their evolution towards clinically refractory angina.

Accuracy of multidetector computed tomography for detection of coronary artery stenosis in acute coronary syndrome compared with stable coronary disease: a CORE64 multicenter trial substudy.

BACKGROUND: Multi-detector computed tomography angiography (MDCTA) is a promising method for risk assessment of patients with acute chest pain. However, its diagnostic performance in higher-risk patients has not been investigated in a large international multicenter trial. Therefore, in the present study we sought to estimate the diagnostic accuracy of MDCTA to detect significant coronary stenosis in patients with acute coronary syndrome (ACS). METHODS: Patients included in the CORE64 study were categorized as suspected-ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before invasive coronary angiography (ICA) and both exams were evaluated by blinded, independent core laboratories. RESULTS: From 371 patients included, 94 were categorized as suspected ACS and 277 as non-ACS. Patient-based analysis showed an area under the receiver-operating-characteristic curve (AUC) for detecting ≥ 50% coronary stenosis of 0.95 (95% CI: 0.88-0.98) in ACS and 0.92 (95% CI: 0.88-0.95) in non-ACS group (P=0.29). The sensitivity, specificity, positive and negative predictive values of MDCTA were 0.90(0.80-0.96), 0.88(0.70-0.98), 0.95(0.87-0.99) and 0.77(0.58-0.90) in suspected ACS patients and 0.87(0.81-0.92), 0.86(0.79-0.92), 0.91(0.85-0.95) and 0.82(0.74-0.89) in non-ACS patients (P NS for all comparisons). The mean calcium scores (CS) were 282 ± 449 in suspected ACS and 435 ± 668 in non-ACS group. The accuracy of CS to detect significant coronary stenosis was only moderate and the absence or minimal coronary artery calcification could not exclude the presence of significant coronary stenosis, particularly in ACS patients. CONCLUSIONS: The diagnostic accuracy of MDCTA to detect significant coronary stenosis is high and comparable for both ACS and non-ACS patients.

The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease.

OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease.

Lipid transfers to HDL are predictors of precocious clinical coronary heart disease.

BACKGROUND: High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function. METHODS: Thirty normocholesterolemic CAD patients aged <50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol, cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL. RESULTS: LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8±1.2%vs 7.0±3.3%,p<0.0001) and triglycerides (3.7±1.7%vs 4.9±1.9%, p=0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5±1.9%vs 4.8±1.8%, p=0.0008); phospholipid transfer was equal (17.8±3.5% vs 19.5±3.9%). CONCLUSION: Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies.

Outcome of adults with asymptomatic severe aortic stenosis.

OBJECTIVES: To evaluate clinical and echocardiographic variables that could be used to predict outcomes in patients with asymptomatic severe aortic valve stenosis. Management of asymptomatic severe aortic stenosis is controversial. Because prophylactic surgery may be protective, independent predictors of events that could justify early surgery have been sought. METHODS: Outpatients (n=133; mean [+/-SD] age, 66.2+/-13.6 years) with isolated severe asymptomatic aortic stenosis but normal left ventricular function and no previous myocardial infarction were followed up prospectively at a tertiary care hospital. INTERVENTIONS: We use a "wait-for-events" strategy. Clinical and echocardiographic variables were analyzed. RESULTS: Nineteen patients developed angina; 40, dyspnea; 5, syncope; and 7, sudden death during a mean follow-up period of 3.30+/-1.87 years. Event-free survival was 90.2+/-2.6% at 1 year, 73.4+/-3.9% at 2 years, 70.7+/-4.3% at 3 years, 57.8+/-4.7% at 4 years, 40.3+/-5.0% at 5 years, and 33.3+/-5.2% at 6 years. The mean follow-up period until sudden death (1.32+/-1.11 years) was shorter than that for dyspnea (2.44+/-1.84 years), syncope (2.87+/-1.26 years) and angina (3.03+/-1.68 years). Cox regression analysis disclosed only reduced but within normal limits ejection fraction as independent predictor of total events. CONCLUSIONS: Management on "wait-for-events" strategy is generally safe. Progressive left ventricular ejection fraction reduction even within normal limits identified patients at high risk for events in whom valve replacement surgery should be considered.

The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease

OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease. .

The S447X polymorphism of lipoprotein lipase: effect on the incidence of premature coronary disease and on plasma lipids.

OBJECTIVE: The objective of this study was to evaluate the effect of polymorphism S447X on plasma lipids of patients with premature coronary artery disease (CAD). METHODS: Plasma lipids and genotypes were determined in 2 groups: 313 patients with premature CAD (<55 years of age) and 150 controls without CAD. RESULTS: Frequency of the S447X polymorphism was 18% in patients with CAD and 23% in the control group. The S447X polymorphism of lipoprotein lipase is related to a decrease in plasma triglyceride concentrations in male patients with CAD, but this correlation is not observed in female patients. CONCLUSION: The presence of the S447X lipoprotein lipase polymorphism was not associated with the incidence of CAD.