Agnieszka Sędkowska

A Common Variant in Low-Density Lipoprotein Receptor–Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol

Objective—A rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). Methods and Results—Twelve common (minor allele frequency ≥0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (P=0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex-, and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations − 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (P=0.0268, P=0.0476, and P=0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex-, and BMI-adjusted LDL-C (SE=0.05, P=0.0038). Conclusions—Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation.

The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively

BackgroundDiabetes (DM) deteriorates the prognosis in patients with coronary heart disease. However, the prognostic value of different glucose abnormalities (GA) other than DM in subjects with acute myocardial infarction (AMI) treated invasively remains unclear.AimsTo assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention (PCI).MethodsA single-center, prospective registry encompassed 2733 consecutive AMI subjects treated with PCI. In all in-hospital survivors (n = 2527, 92.5%) without the history of DM diagnosed before or during index hospitalization standard oral glucose tolerance test (OGTT) was performed during stable condition before hospital discharge and interpreted according to WHO criteria. The mean follow-up period was 37.5 months.ResultsThe incidence of GA was as follows: impaired fasting glycaemia - IFG (n = 376, 15%); impaired glucose tolerance - IGT (n = 560, 22%); DM (n = 425, 17%); new onset DM (n = 384, 15%); and normal glucose tolerance – NGT (n = 782, 31%). During the long-term follow-up, death rate events for previously known DM, new onset DM and IGT were significantly more frequent than those for IFG and NGT (12.3; 9.6 and 9.4 vs. 5.6 and 6.4%, respectively, P < 0.05). The strongest and common independent predictors of death in GA patients were glomerular filtration rate < 60 ml/min/1,73 m^2 (HR 2.0 and 2.8) and left ventricle ejection fraction < 35% (HR 2.5 and 1.8, all P < 0.05) respectively.ConclusionsGlucose abnormalities are very common in AMI patients. DM, new onset DM and IGT increase remote mortality. Impaired glucose tolerance bears similar long-term prognosis as diabetes.

Prognostic significance of HbA1c in patients with AMI treated invasively and newly detected glucose abnormalities

Background Glucose abnormalities are frequent comorbidities influencing prognosis in patients with cardiovascular diseases. The objective of this study was to evaluate prognostic role of HbA1c in patients with acute myocardial infarction (AMI) treated invasively, who had newly detected glucose abnormalities. Design Single-centre registry encompassed 2146 survivors of AMI. In all patients without diabetes mellitus (DM), oral glucose tolerance test was performed before hospital discharge and interpreted according to the guidelines. Methods From the study population, two major groups with defined new glucose abnormalities and estimated HbA1c were selected: 457 patients with impaired glucose tolerance (IGT) and 306 patients with newly detected DM (newDM). In each of these groups, the median value of HbA1c was calculated and established as the cut-off point for further analysis. The median HbA1c for IGT group was 5.9% and for newDM was 7.0%. Results Patients with IGT and HbA1c ≤ 5.9% had significantly lower posthospital mortality (4.5%) than those with HbA1c >5.9% (25.0%; p<0.001). Similarly, patients with newDM and HbA1c ≤7.0% had lower mortality (6.4%) than those with HbA1c >7.0% (14.3%; p<0.05). Multivariate regression analysis revealed that increase of HbA1c was one of the strongest independent risk factors of death among IGT patients (HR 2.9, 95% CI 2.7–3.1; p < 0.001) and newDM (HR 1.53, 95% CI 1.39–1.66; p<0.05). Conclusions Increase of HbA1c in patients with newly detected glucose abnormalities was associated with significantly reduced survival after AMI treated invasively. Moreover, increase of HbA1c in patients with IGT and newDM was one of the strongest independent risk factors of death in these populations.

The significance of heart rate turbulence in predicting major cardiovascular events in patients after myocardial infarction treated invasively.

Introduction: The role of heart rate turbulence (HRT) related to baroreflex sensitivity in predicting mortality after myocardial infarction (MI) has been confirmed by several investigators. However, the significance of HRT in predicting major adverse cardiovascular events (MACE) following acute MI is unknown.

The impact of unsuccessful percutaneous coronary intervention on short- and long-term prognosis in STEMI and NSTEMI.

Objectives: To compare the impact of the efficacy of percutaneous coronary intervention (PCI) on prognosis in ST and non‐ST elevation myocardial infarction (STEMI and NSTEMI) patients with respect to infarct‐related artery (IRA). Background: The significance of the efficacy of PCI in STEMI and NSTEMI depending on the type of IRA has yet to be clarified. Methods: Study population consisted of 2,179 STEMI and 554 NSTEMI consecutive patients treated with urgent PCI. The efficacy of PCI (TIMI [thrombolysis in myocardial infarction] 3 vs. TIMI < 3) was assessed with regard to the type of IRA (left anterior descending artery, circumflex artery [Cx] or right coronary artery). The mean follow‐up was 37.5 months. Results: The rate of unsuccessful PCI was similar in STEMI and NSTEMI irrespectively of IRA (14.1 vs. 17.7%; P = 0.062). In STEMI, unsuccessful PCI was associated with significantly higher early (23.1 vs. 5.6%; P < 0.001) and late (29.9 vs. 12.8%; P < 0.001) mortality regardless of IRA. In NSTEMI, the inefficacious PCI significantly increased early (19.0% vs. 0.9%; P < 0.001) and late (27.3% vs. 6.3%; P < 0.001) mortality only in patients with Cx‐related infarction. Unsuccessful PCI of IRA was an independent risk factor for death in STEMI (HR 1.64; P < 0.05), but not in NSTEMI (P = 0.64). Further analysis showed that whilst unsuccessful PCI of any vessel in STEMI is an independent risk factor for death, in NSTEMI this applies to unsuccessful PCI of Cx only. Conclusions: The significance of unsuccessful PCI of IRA seems to be different in STEMI and NSTEMI. Unsuccessful PCI is an independent risk factor for death in STEMI regardless of IRA and in NSTEMI with the involvement of Cx.

The risk of stroke in patients with acute myocardial infarction treated invasively.

BackgroundTo assess the incidence, clinical significance, and independent risk factors of stroke in patients with acute myocardial infarction (AMI) treated invasively. Materials and methodsWe analyzed 2520 consecutive patients with AMI admitted between 2003 and 2007. Data on long-term follow-up were screened to identify patients who had stroke. ResultsDuring a median of 25.5 months, 52 patients (2.07%) had stroke. The cumulative risk of stroke was the highest during the first year (1.23%) and particularly within the first month after AMI (0.28%). Patients with stroke were at a significantly higher risk of developing major adverse cardiovascular events, including repeated AMI (26.9 vs. 14.6%, P<0.05) and death (40.4 vs. 13.6%, P<0.001). Previous stroke [hazard ratio (HR) 5.89], female sex (HR 2.60), glomerular filtration rate <60 ml/min/1.73 m2 (HR 1.92), and contrast nephropathy (HR 1.87, all P<0.05) were independent predictors of stroke. The receiver-operating curve calculated for the Contrast nephropathy, renal Insufficiency, Female, prior Stroke (CIFS) risk scale demonstrated a significant predictive value of this scale (area under curve 0.73, P<0.001). Patients with the lowest, median, and highest risk scores (<4, 4–5, ≥6 points, respectively) differed significantly with regard to stroke incidence (2.1 vs. 7.9 vs. 14.0%, respectively, P<0.05). ConclusionThe risk of stroke is the highest within the first month after AMI. Stroke is a marker of unfavorable outcome in this population. Independent risk factors for stroke after invasive treatment of AMI are different from those commonly perceived as stroke predictors. A risk scale based on sex, stroke history, and renal impairment is useful in risk stratification.

The incidence and risk factors of stroke in patients with acute myocardial infarction treated invasively and concomitant impaired renal function

BACKGROUND Impaired renal function is a marker of poor prognosis in patients with acute myocardial infarction (AMI). The aim of the study was to assess the incidence and independent predictors of stroke in population of patients with AMI treated invasively and concomitant impaired renal function (IRF). METHODS We analyzed 2,520 consecutive AMI patients admitted to our Center between 2003 and 2007 and treated with percutaneous coronary intervention. The whole population was divided into patients with IRF, defined as glomerular filtration rate < 60 mL/min/1.73 m(2) or contrast induced nephropathy (IRF group, n = 933; 37.02%) and patients without IRF (control group, n = 1587; 62.98%). The IRF group was subjected to further analysis. Data on long-term follow-up were screened to identify the patients who experienced stroke. RESULTS During median of 25.5 months of follow-up 52 (2.07%) the patients experienced stroke - 33 (3.54%) in the IRF group and 19 (1.2%) patients in the control group. The risk of major adverse cardiovascular events in the IRF group, including repeated AMI (68.8 vs.14.9%, p < 0.001) and death (45.5 vs. 25.1%, p < 0.05) was significantly higher in patients with stroke. Previous stroke (HR 6.85), female gender (HR 3.13), as well as STEMI anterior (HR 2.55) were independent risk factors of stroke in this population. CONCLUSIONS Patients with AMI treated invasively and concomitant IRF were at higher risk of stroke occurrence in the future. Stroke was associated with poor outcome in the studied population. Independent predictors of stroke in patients with IRF and AMI treated invasively were different from commonly recognized stroke predictors.