Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.

BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

Heart failure-related quality-of-life impairment after myocardial infarction.

AIMS: Recent advances in therapy led to a significant decrease in mortality and morbidity after myocardial infarction (MI). However, little is known about quality of life (QoL) after MI. We examined heart failure (HF)-related quality-of-life (QoL) impairment, its trajectories, and determinants after MI. METHODS: Data from a single-center prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were utilized. At 1 month and 1 year after hospital discharge, patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: In total, 850 patients (aged 65 ± 12 years, 27% female) hospitalized between June 2017 and October 2020 completed KCCQ at 1 month after discharge. Of these, 38.7% showed HF-related QoL impairment (KCCQ ≤ 75). In addition to characteristics of MI (MI size, diuretics need, heart rate), comorbidities as renal dysfunction and anemia were associated with QoL impairment. Of the 673 eligible, 500 patients (74.3%) completed KCCQ at 1 year after MI. On average, QoL improved by 5.9 ± 16.8 points during the first year after MI (p < 0.001); but, in 18% of patients QoL worsened. Diabetes control and hemoglobin level at the time of hospitalization were associated with QoL worsening. CONCLUSION: Two out of 5 patients after MI present with HF-related QoL impairment. In addition to guideline-directed MI management, careful attention to key non-cardiac comorbidities as chronic kidney disease, anemia and diabetes may lead to further augmentation of the benefit of modern therapies in terms of QoL.

Very low lipoprotein(a) and increased mortality risk after myocardial infarction.

BACKGROUND: Inconclusive data exist on risk associated with Lp(a) in patients after myocardial infarction (MI). Aims of the present study were to evaluate the association of Lp(a) level with total mortality and recurrent cardiovascular events. DESIGN AND METHODS: Single center prospective registry of consecutive patients hospitalized for acute myocardial infarction between June 2017 and June 2020 at a large tertiary cardiac center with available blood samples drawn <24h of admission. RESULTS: Data from 851 consecutive patients hospitalized for MI were evaluated. During the median follow-up of 19 months (interquartile range 10-27), 58 (6.8%) patients died. Nonlinear modelling revealed a U-shaped association between Lp(a) and total mortality risk. Compared to patients with Lp(a) ranging between 10-30 nmol/L and after multivariate adjustment, total mortality risk was increased both in patients with Lp(a)<7 nmol/L (hazard ratio (HR) 4.08, 95% confidence interval (CI) 1.72-9.68) and Lp(a) ≥125 nmol/L (HR 2.92, 95% CI 1.16-7.37), respectively. Similarly, the risk of combined endpoint of acute coronary syndrome recurrence or cardiovascular mortality was increased both in patients with low (sub-HR 2.60, 95% CI 1.33-5.08) and high (sub-HR 2.10, 95% CI 1.00-4.39) Lp(a). Adjustment for heart failure signs at the time of hospitalization weakened the association with total mortality and recurrent cardiovascular events. CONCLUSIONS: In the present analysis, both high and low concentrations of Lp(a) were associated with an increased risk of total mortality and recurrent cardiovascular events after MI. The excess of mortality associated with Lp(a) was partially attributable to more prevalent heart failure.

Heart failure after myocardial infarction: incidence and predictors.

AIMS: The aim of the present paper was to provide an up-to-date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction. METHODS AND RESULTS: Based on literature review, several clinical risk factors and biochemical, genetic, and imaging biomarkers were identified to predict the risk of HF development after myocardial infarction. CONCLUSIONS: Heart failure is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development using a multimodality approach, and early initiation of guideline-directed HF therapy in these patients, can decrease the HF burden.

MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome.

BACKGROUND: Genome-wide association studies (GWAs) focused on cardiovascular diseases reveal variants within genes which have not been analyzed through the pre-GWAs era, and whose function is often unknown. One of them is variant rs9818870 at the MRAS gene locus. OBJECTIVES: To analyze if MRAS polymorphism is associated with acute coronary syndrome (ACS) risk in a Czech population and with mortality in male patients after myocardial infarction. MATERIAL AND METHODS: 1,779 male patients with ACS (aged 55.3 ±7.9 years) and 673 female patients with ACS (aged 64.0 ±8.1 years) were genotyped for rs9818870 polymorphism using the PCR-RFLP method. In a subset of 1,221 patients, detailed diagnoses (901 subjects with STEMI, 280 subjects with NSTEMI, 40 cases with unstable angina pectoris) were recorded. In 1,614 males, records about total and cardiovascular mortality were available. RESULTS: Whether the entire populations or males and females have been analyzed separately or not, we have not confirmed the described association between DNA marker rs9818870 and ACS in Czechs (30.4% vs 29.4% carriers of the minor T allele [recessive model], p = 0.54; OR 1.05; 95% CI 0.89-1.24 for males and 32.1% vs 29.7% carriers of the minor T allele, p = 0.28; OR 1.12; 95% CI 0.91-1.37 for females). Types of the ACS (STEMI and NSTEMI) or mortality (in males only) were not associated with the analyzed polymorphism (all p > 0.34). CONCLUSIONS: The rs9818870 variant is not associated with ACS or mortality in ACS patients in the Czech Slavonic population.

Genetic variants within telomere-associated genes, leukocyte telomere length and the risk of acute coronary syndrome in Czech women.

The association between leukocyte telomere length (LTL) and cardiovascular disease (CVD) has been published in many reports, although almost exclusively in men. In our study we analysed the association between LTL and five selected variants within three candidate genes (TERC rs12696304; TERF2IP rs3784929 and rs8053257; UCP2 rs659366 and rs622064), which are not only involved in telomere-length maintenance but also potentially associated with higher risk of acute coronary syndrome (ACS) in Czech women (505 cases and 642 controls). We detected significantly shorter LTL in women with ACS (P<0.001), but the difference disappeared after multiple adjustments. We did not find any significant associations between analysed variants and LTL, except for rs622064 within the UCP2 gene, in which case AA homozygotes had a higher LTL (P<0.04). Genotype frequencies of the analysed SNPs did not differ between controls and women with ACS. Variants within UCP2 (rs622064; CC vs. A allele carriers OR=1.61; 95% CI: 1.21-2.15, P<0.002) and within TERF2IP (rs8053257; A allele carriers vs. GG, OR=1.78; 95% CI: 1.07-3.18, P<0.03) were associated with increased risk of type 2 diabetes mellitus (T2DM). Analysed polymorphisms were not major determinants of telomere length or ACS risk in Czech females.

Lack of an association between connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 and lymphotoxin-alpha genes and acute coronary syndrome in Czech Caucasians.

BACKGROUND: The majority of acute coronary syndrome (ACS) cases cannot be explained by the analysis of commonly recognized risk factors; thus, the analysis of possible genetic predispositions is of interest. The genes for connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 (PAI-1) and lymphotoxin-alpha are among many presently known candidate genes that are associated with risk factors for ACS. OBJECTIVE: To identify the potential impact of the functional variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha on ACS in a Caucasian Czech population. METHODS: A total of 1399 consecutive patients (1016 men and 383 women) with ACS from five coronary care units located in Prague (Czech Republic) were analyzed; a representative sample of 2559 healthy individuals (1191 men and 1368 women) were also genotyped and served as controls. RESULTS: The gene variants analyzed were not significantly associated with the prevalence of ACS or the classical risk factors of ACS development such as high plasma lipid levels, hypertension, diabetes, high body mass index or smoking. CONCLUSION: In a Caucasian Czech population sample, genetic variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha were not significantly associated with a predisposition toward ACS.

A FTO variant and risk of acute coronary syndrome.

BACKGROUND: The FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-case mortality. METHODS: We have analyzed the FTO rs17817449 variant in consecutive 1092 male patients with acute coronary syndrome (ACS) and in 1191 randomly selected Caucasian individuals (population controls). RESULTS: The FTO variant was significantly associated with BMI both in controls (P<0.02) and ACS patients (P<0.01). In both groups, BMI was highest in GG homozygotes and lowest in TT homozygotes. There was a significant difference between the ACS patients and controls in the frequency of the FTO genotype GG (21.4% vs. 15.9%, P<0.005). FTO GG homozygotes had a significantly increased risk of ACS, compared with TT homozygotes which was independent of age and BMI (odds ratio 1.49, 95% confidence interval 1.16-1.93). The odds ratio of ACS patients for the GG genotype remained significant even after the exclusion of diabetics (100 controls and 339 ACS patients), with OR 1.32 (95% CI 1.01-1.72). CONCLUSIONS: This study provides an evidence of an association between the FTO variant and risk of ACS in Caucasian males.

High-sensitivity C-reactive protein concentration in patients with myocardial infarction-environmental factors, and polymorphisms in interleukin-10 and CD14 genes.

BACKGROUND: It has been shown that high-sensitivity C-reactive protein (hsCRP) concentrations are associated with elevated risk of myocardial infarction, but the mechanisms regulating hsCRP concentration are not completely elucidated yet. In our study, association of interleukin-10 (IL-10) and CD14 polymorphisms and environmental factors with the risk of myocardial infarction was studied. METHODS: The study group consisted of 284 male patients aged below 65 years, admitted to hospital for myocardial infarction. The controls were age-matched individuals selected from a 1% representative population sample of adult men. RESULTS: While there was no difference in body mass index (BMI), the patients more frequently had abdominal-type obesity. hsCRP concentration was higher in patients (2.12+/-2.31 mg/L) than in controls (1.40+/-1.56 mg/L; p=0.001), in spite of statin treatment in most of the patients. No significant difference in lipoprotein concentrations was found. There was no difference in IL-10 and CD14 genotype distributions between the patients and controls. In smoking patients carrying the CD14 C allele, hsCRP concentration was significantly higher (p=0.0012) than in a non-smoking patients with the same allele. According to linear regression analysis, statin treatment was the only variable with an influence that reached statistical significance in the patient group, while in the control group, age, smoking, education and BMI significantly influenced hsCRP concentration. CONCLUSIONS: There was no association between IL-10 and CD14 polymorphisms and myocardial infarction occurrence. Gene-environment interaction may play an important role in influencing hsCRP concentration.