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.

[Acute myocardial infarction in young patients--severe failures in the system of acute and secondary care]. / Akutní infarkt myokardu u mladých nemocných - závazné nedostatky v systému akutní a následné péce.

INTRODUCTION: The incidence of cardiovascular (CV) diseases and acute myocardial infarction (AMI) in Czech Republic is de-clining. In spite of this in a proportion of patients AMI occurs in young age. The aim of our project was to assess the character of risk factors, precipitating diseases and the quality of care in young AMI survivors. METHODS: We included 132 patients (97 men and 35 women) in whom AIM with ST elevations occurred before age of 45 years in men and age of 50 years in women. Several results were compared to a control group composed of 84 healthy volunteers of comparable age. We assessed the course of the disease, extent of coronary involvement, subsequent therapy and control of risk factors after 3 years from the index event. RESULTS: Smoking represented the main risk factor - 85% patents were active smokers at the time of AMI and 9% were former smokers, 64% patients had a positive family history of CV disease. We found a higher prevalence of dyslipidemia history in men. In spite of high rate of statin use, laboratory examination during follow-up revealed higher triglyceride values and low levels of HDL-cholesterol in both genders. All together 23% of patients had a history of provoking underlying disease or precipitating factors (inflammatory diseases, malignancies, combined thrombophilias, drug abuse). In total 95% of patients underwent coronary angiography during the acute phase of AMI, the median time from pain onset to intervention was 9 hours. Most patients had single vessel disease, 14% had even coronary angiogram without clinically significant stenosis. The subsequent care was satisfactory concerning the rate of drug prescriptions. However, target lipid values were not reached in 78% patients and blood pressure targets in 37%. CONCLUSIONS: In patients who suffered AMI in young age, risk factors are dominated by smoking and positive family history of CV diseases. One fifth of patients suffer from other underlying disease (inflammatory disease, malignancies, combined thrombophilia) or have another precipitating factor (febrile disease, drug abuse). The acute care seems unsatisfactory due to late arrival of most patients to catheterization laboratories (underestimation of the disease, incorrect initial diagnosis). Subsequent therapy is well composed but lacks in intensity.

CCAAT/enhancer-binding protein alpha (CEBPA) polymorphisms and mutations in healthy individuals and in patients with peripheral artery disease, ischaemic heart disease and hyperlipidaemia.

The CCAAT/enhancer-binding protein alpha, encoded by the intronless CEBPA gene, is a transcription factor that induces expression of genes involved in differentiation of granulocytes, monocytes, adipocytes and hepatocytes. Both mono- and bi-allelic CEBPA mutations were detected in acute myeloid leukaemia and myelodysplastic syndrome. In this study we also identified CEBPA mutations in healthy individuals and in patients with peripheral artery disease, ischaemic heart disease and hyperlipidaemia. We found 16 various deletions with the presence of two direct repeats in CEBPA by analysis of 431 individuals. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493- 498_865-870), GG (486-487_885-886), and GCCAAGCAGC (508-517_907-916), all according to GenBank Accession No. NM_004364.2. In one case we identified that a father with ischaemic heart disease and his healthy son had two identical deletions (493_864del and 508_906del, both according to GenBank Accession No. NM_004364.2) in CEBPA. The occurrence of deletions between two repetitive sequences may be caused by recombination events in the repair process. A double-stranded cut in DNA may initiate these recombination events in adjacent DNA sequences. Four types of polymorphisms in the CEBPA gene were also detected in the screened individuals. Polymorphism in CEBPA gene 690 G>T according to GenBank Accession No. NM_004364.2 is the most frequent type in our analysis. Statistical analysis did not find significant differences in the frequency of polymorphisms in CEBPA in patients and in healthy individuals with the exception of P4 polymorphism (580_585dup according to GenBank Accesion No. NM_004364.2). P4 polymorphism was significantly increased in ischaemic heart disease patients.

Fabry disease - Vascular manifestations.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by the deficient activity of alpha-galactosidase A which results in the accumulation of neutral glycosphingolipids in various tissues leading particularly to vasculopathy, cardiomyopathy, neuropathy, and chronic kidney disease. It results in substantial morbidity and premature death in affected patients. Although there are some signs and symptoms suggestive of FD including painful crisis, angiokeratomas, and corneal changes, the majority of FD complications are non-specific (left ventricular hypertrophy, conduction abnormalities, vascular spasms, proteinuria, renal insufficiency), which is why FD still remains largely underdiagnosed. The mechanism by which accumulating glycosphingolipids cause multiorgan disorder is not yet completely understood as it cannot be explained by pure substrate storage. Besides standard therapy of different medical problems in FD patients, specific enzyme replacement therapy has been introduced in the last few years.

[Overcooling during mild hypothermia in cardiac arrest survivors--phenomenon we should keep in mind]. / Nadmerné othlazení behem mírné hypotermie po srdecní zástave--fenomén zasluhující pozornost.

BACKGROUND: Mild hypothermia (MH) in cardiac arrest survivors has became a routine part of early postresuscitative support. Overcooling is a frequent phenomenon with the unknown outcome. AIM OF THE STUDY: To analyze the incidence and outcome ofovercooling below body core temperature (BT) of 32 degrees C. MATERIAL AND METHODS: We performed retrospective analysis of all 56 consecutive cardiac arrest survivors treated by MH who reached therapeutic BT in the 2nd Department of Internal Medicine, General Teaching Hospital, Prague. MH was initiated as soon as possible after the return of spontaneous circulation to reach BT of 33 degrees C followed by maintainance of BT 32-34 degrees C for 12 hours. Patients were cooled by surface cooling via ice-packs and by interavenous infusion of cold crystaloids. RESULTS: Overcooling below BT of 32 degrees C was observed in 23 patients (41%). This group of patients had more frequently asystole as the initial rhythm (34.8 vs 9.1%), more frequently were cooled by combinatory cooling approach (56.5 vs 27.3%), more frequently had lower baseline BT (35.3 +/- 1.3 vs 36.2 +/- 1.2 degrees C), higher cooling rate (the interval required for a decrease of BT by 1 degrees C 61.5 +/- 53.1 vs 90.1 +/- 50.0 min) (all p < 0.05) than patients with proper profile of BT during MH. Overcooling was independent negative predictor of discharge favourable neurological outcome (OR 0.16, 0.022-0.77, p = 0.037). CONCLUSION: Induction of MH by conventional cooling approach is burdened by high risk of overcooling. This phenomenon is probably associated with worse outcome.

Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome.

BACKGROUND: Induction of mild hypothermia (MH) in patients resuscitated from cardiac arrest improves their outcome. However, benefits and risks of MH in patients who remain in cardiogenic shock after the return of spontaneous circulation (ROSC) are unclear. We analysed all cardiac arrest survivors who were treated with MH in our intensive coronary care unit (CCU) and compared the outcome of patients with cardiogenic shock syndrome (CSS) with those who were circulatory stable. METHODS: We performed retrospective analysis of all consecutive cardiac arrest survivors treated by MH in our CCU from November 2002 to August 2006. They were classified into two groups, according to whether they met the criteria for cardiogenic shock or not before MH initiation. RESULTS: Out of 56 consecutive patients, 28 fulfilled criteria of cardiogenic shock before MH initiation (group A) and 28 were relatively stable (group B). In-hospital mortality was 57.1% in group A and 21.4% in group B patients (P=0.013). Favourable neurological outcome anytime during hospitalization was found in 67.9% of group A patients and in 82.1% of group B subjects (P=0.355). Favourable discharge neurological outcome was reached in 39.3% in group A and in 71.4% in group B (P=0.031). The complication rate in both groups did not differ. CONCLUSION: While in-hospital mortality in cardiac arrest survivors treated by MH was expectably higher in those with cardiogenic shock than in stable patients, the favourable neurological outcome during hospitalization was comparable in both groups. Therefore, induction of MH should be considered in cardiac arrest survivors with CSS after ROSC.