Traditional risk factors of acute coronary syndrome in four different male populations - total cholesterol value does not seem to be relevant risk factor.

Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80+/-1.11 vs. 5.76+/-1.06 mmol/l in Czechs; 5.32+/-1.32 vs. 5.71+/-1.08 mmol/l in Lithuanians; 4.88+/-1.05 vs. 5.38+/-1.13 mmol/l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles.

Gene variants at FTO, 9p21, and 2q36.3 are age-independently associated with myocardial infarction in Czech men.

AIM: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in developed countries. This study aimed to confirm the effect of common putative CVD-associated gene variants (FTO rs17817449, KIF6 rs20455, 9p21 rs10757274 and 2q36.3 rs2943634) on CVD manifestation, and determine whether this effect differs between younger (< 50 years) and older CVD patients. METHODS: 1191 controls and 1889 MI patients were analyzed. All participants were Caucasian Czech males aged <65 years (532 were <50 years) who were examined at cardiology clinics in Prague, Czech Republic. Variants of FTO, 9p21, 2q36.3, and KIF-6 were genotyped using PCR-RFLP or TaqMan assay. RESULTS: Variants of FTO (OR 1.48; 95% CI, 1.19-1.84 in a TT vs. GG comparison, p=0.0005); 9p21 (OR 1.74; 95% CI, 1.41-2.14 in an AA vs. GG comparison, p=0.0001); and 2q36.3 (OR 1.34; 95%CI, 1.09-1.65 in an AA vs. +C comparison, p=0.006) were significantly associated with MI in the male Czech population. In contrast, genotype frequencies of KIF-6 (rs20455) were the same in patients and controls (P=1.00). Nearly identical results were observed when a subset of young MI patients (N=532, aged <50 years) was analyzed. CONCLUSION: We confirmed the importance of determining FTO, 9p21, and 2q36.3 variants as part of the genetic determination of MI risk in the Czech male population.

Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the traditional risk factors for MI are responsible for approximately 50% of cases of MI cases. Attention therefore has recently focused on genetic variants that are not associated with conventional risk factors. One of them is the marker rs6922269, which has been suggested as a risk factor for development of MI in Western populations. We analyzed the relationship between rs6922269 variant on MTHFD1L gene and (i) risk of the acute coronary syndrome (ACS) in the Czech population and (ii) mortality in 7 years follow up. Rs6922269 (G>A) variant was analyzed (CR 99.3% for patients and 98.0% for controls) by PCR-RFLP in consecutively examined 1614 men and 503 women with ACS (age below 65 years) and in population-based controls--1191 men and 1368 women (aged up to 65 years). ANOVA and Chi square were used for statistical analysis. The genotype frequencies were almost identical (P=0.87) in the ACS patients and in controls and no differences were observed, if males (P=0.73) and females (P=0.93) were analysed separately. In addition, rs6922269 polymorphism was not associated with the classical risk factors (dyslipidemia, hypertension, obesity, smoking, diabetes) in control population. Cardiovascular mortality was significantly higher in males, carriers of the AA genotype (P<0.001, OR 2.52, 95% CI 1.40-4.55, for AA vs. +G). We conclude, that rs6922269 variant at MTHFD1L gene could be an important prognostic factor for cardiovascular mortality in patients after ACS.

Association between a marker on chromosome 9 and acute coronary syndrome. confirmatory study on Czech population.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the classical risk factors for MI are responsible for approximately 50 % of MI cases. Attention has therefore recently been attracted to those genetic variants that are not associated with conventional risk factors. One of them is the marker rs10757274 in the "genefree" zone on chromosome 9, which has been repeatedly recognized as a risk factor for development of MI in Western populations. We analysed the relationship between the rs10757274 variant on chromosome 9 and risk of the acute coronary syndrome (ACS) in Czech population. The rs10757274 (A > G) variant was successfully analysed (CR = 99.4 % for patients and 98.4 % for controls) by PCR-RFLP in consecutively examined 1,046 men and 281 women with ACS (age below 65 years) and in population-based controls - 1,162 men and 1,355 women (aged up to 65 years). ANOVA and χ2 were used for statistical analysis. We confirmed that GG homozygotes are more frequent (codominant model of analysis) among patients with myocardial infarction than in the control group both in men (28.5 % vs. 22.0 %, P = 0.0001, OR 1.73, 95 % CI 1.36-2.19) and women (32.0 % vs. 24.6 %, P = 0.02, OR 1.62, 95 % CI 1.13-2.34). However, rs10757274 polymorphism was not associated with the classical risk factors either in control population or in ACS patients. We conclude that the rs10757274 variant at 9p23.1 is an important genetic risk factor for ACS development in the Czech population.

Does angiotensin-converting enzyme polymorphism influence the clinical manifestation and progression of heart failure in patients with dilated cardiomyopathy?

To evaluate the role of angiotensin-converting enzyme (ACE) polymorphism on the development of end-stage dilated cardiomyopathy, the ACE gene polymorphism of 90 patients after heart transplantation because of this disease was compared with the population sample. No difference in gene frequencies was found, but when compared with the population sample there were fewer ID heterozygotes detected; no significant influence of ACE polymorphism on the course of the disease before transplantation was found.

[Heart transplantation at the Institute of Clinical and Experimental Medicine in Prague]. / Transplantace srdce v Institutu klinické a experimentální medicíny v Praze.

In the Institute of Clinical and Experimental Medicine in Prague 101 orthotopic allotransplantations of the heart were performed in 100 patients (87 men and 13 women). The reason for transplantation were terminal stages in the first place dilated cardiomyopathies and ischaemic heart disease. 58% of the patients survive after transplantation, the mortality rate is 42%. The highest mortality is in the early postoperative period (within two weeks after operation)--21 cases (50%). The longest survival period is nine years and six months. All patients have cyclosporin immunosuppressive treatment (in combination with another drug, later with another two drugs). In the authors' group in particular incipient acute rejections are encountered, "mild" rejections are less frequent and "moderate" rejections least frequent. The patients do not reach the stage of advanced acute rejection, i.e. "severe" rejection. Acute rejections are treated as a rule with 3 g Urbason. After this treatment acute rejection improves as a rule completely after one or two weeks therapy.

[The patient after heart transplantation]. / Obraz nemocného po srdecní transplantaci.

The data of the first 100 patients undergoing heart transplantation in the period between January 1984 and May 1993 were analyzed. Of this group, 57 patients are alive. Out of the total of 43 deaths, 14 patients died from graft failure within the first postoperative days, 6 died from surgical complications, 11 from infection, 10 deaths were due to accelerated coronary atherosclerosis, and 2 patients died from tumours. Early mortality rates (within 30 days since surgery) were 37% and 17% in patients operated on between 1984-88 and between 1989-93, respectively. The health condition of heart transplant recipients is affected by side effects of immunosuppressive therapy. Forty per cent of patients re-develop systemic hypertension within the first post-transplantation year. Five years after transplantation, hypertension is detected in 60% of patients. Elevated serum creatinine levels are present in 70% of patients by the end of the first post-transplantation year. In the ensuing period, there is no progression in renal function impairment, which does not require cyclosporin withdrawal and is not associated with the development of hypertension. In the first post-transplantation year, 45% of patients are markedly obese. All patients with overweight and obesity show markedly raised levels of serum cholesterol. Another undesirable effect (mainly due to corticosteroid therapy) is the development of ulcers in 16% of patients. Heart transplantation has become an established method at the Institute for Clinical and Experimental Medicine in Prague. Despite the above pitfalls, heart transplantation substantially prolongs the life of patients and dramatically alters the quality of their life.

[Infectious complications in patients after heart transplantation]. / Infekcní komplikace nemocných po transplantaci srdce.

The incidence of infectious complications was monitored in a group of the first 100 patients undergoing orthotopic heart transplantation at the Institute for Clinical and Experimental Medicine from January 1984 through May 1993. The definition of an infectious complication was a clinically manifest infection requiring treatment. Cytomegalovirus infection and Epstein-Barr virus infection were evaluated by the development of antibody against IgM. A total of 168 infectious complications were detected in 80 patients. The infectious complications were fatal in 11 patients; hence, infections were implicated in 26% of all deaths following heart transplantation. The spectrum of infections markedly varies depending on the interval since the procedure. The most frequent infections within the 30 postoperative days are bacterial (often nosocomial) infections. In the later period (30 days onward), viral infections account for 72% of cases. Of the rarer types of infections, the pulmonary form of aspergillosis was identified in 3 cases, nocardiosis and legionellosis in one case each. Infectious complications were the main cause of deaths in the period of 1 to 4 months post-transplantation, and the spectrum and rate of complications were not different from data reported by other centres.

[Coronary disease in patients after heart transplantation]. / Koronární nemoc u pacientu po transplantaci srdce.

Coronary artery lesions are evaluated in a group of 43 patients surviving for more than 3 months after heart transplantation. An angiographic finding was obtained from 35 patients, autopsy findings were available in eight cases. Angiography demonstrated coronary artery lesions in 12 out of the 35 patients whereas autopsy findings were positive in five out of the eight post mortem examinations. Overall, lesions were found in 40% of patients at a mean follow-up interval of 3.5 years. While the finding of a coronary artery lesion was not related to the classic risk factors for atherosclerosis, an association to a previous cytomegalovirus or Epstein-Barr virus infection was demonstrated. The data suggest that infection caused by the two above viruses is an important factor in the development of vascular lesions in the heart transplant.

[The anticardiolipin syndrome after breast reconstruction]. / Antikardiolipinový syndrom po plastické operaci prsu.

In a 38-year-old patient 17 years previously silicone prostheses of both breasts were implanted. Three years after operation spontaneous abortions developed, later repeated venous and arterial thromboses. Laboratory examinations revealed antibodies against cardiolipin and the diagnosis of anticardiolipin syndrome was established. The authors discuss the relationship between the performed operation and the present disease.

Anticardiolipin syndrome in plastic surgery of the breast.

A 38-year-old female patient had bilateral silicone-made prosthesis implantation performed 17 years ago. Three years after surgery, she had a series of spontaneous miscarriages, later she developed recurrent venous and arterial thromboses. Laboratory tests detected antibodies against cardiolipin and the diagnosis of cardiolipin syndrome was established. The authors discuss the possible association between surgery and the patient's current disease.

[Effect of prolonged administration of beta-blockers on the hemodynamics of patients who have sustained a myocardial infarct]. / Vliianie dlitel'nogo priema beta-blokatorov na gemodinamiku u bol'nykh, perenesshikh infarkt miokarda.

The effect of prolonged treatment with the beta-blocker trimepranol on left-ventricular function was assessed in patients who survived myocardial infarction. Pulmonary arterial catheterization with a floating catheter was used for hemodynamic investigation. Hemodynamic parameters were compared in the treated (20 patients) and control (20 patients matched for age and infarction site) groups. The treated patients showed a reduction in heart rate and cardiac output at rest, as well as stress-induced elevation of the pulmonary arterial pressure and peripheral resistance. Patients with pulmonary hypertension often demonstrated changes of the pressure curve in the pulmonary artery as a possible manifestation of stress-induced mitral regurgitation. Prolonged treatment with trimepranol is associated with increased incidence of pulmonary hypertension in myocardial infarction survivers. The clinical significance of this observation is yet to be established by further studies. Stress-induced mitral regurgitation associated with a mitral subvalvular dysfunction may occasionally be the cause of elevated pulmonary blood pressure.

Left ventricular morphology and function in mild to moderate essential hypertension.

150 males with mild to moderate essential hypertension [EH] were examined echocardiographically and the findings in the left ventricle [LV] were compared with those in 20 normotensive men. Increased LV wall thickness and LV mass was found in 81% and 67% of hypertensives respectively in contrast with a complete absence of LV hypertrophy in normotensives. The former showed also a tendency to the concentric type hypertrophy, which can be considered a characteristic feature of the 2nd stage [WHO] EH. There was an almost uniform incidence of asymmetric septal hypertrophy in the two groups [12 vs. 10%]. Decreased LV end-systolic wall stress in EH was a sign of compensatory myocardial hypertrophy without LV dilatation. The hypertensives exhibited a normal or slightly elevated systolic LV function. On the other hand, some indirect indices of LV properties [peak rate of LV relaxation and left atrial dimension] were indicative of diastolic function impairment. A slight but significant correlation between the degree of LV hypertrophy and systemic blood pressure at rest was found in a part of hypertensive patients. The study indicates that mild to moderate EH leads to some changes in LV morphology and function, which can be easily recognized by echocardiography.