Impact of genetic and clinical factors on dose requirements and quality of anticoagulation therapy in Polish patients receiving acenocoumarol: dosing calculation algorithm.

BACKGROUND: Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves. OBJECTIVE: The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm. MATERIALS AND METHODS: We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors. RESULTS: We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04). CONCLUSION: Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

Mortality from ischaemic heart disease in Poland in 1991-1996 estimated by the coding system used since 1997.

BACKGROUND: Official statistical data on deaths due to heart disease and cerebrovascular disease in Poland in 1991-2005 are not consistent because of the changes in the coding system introduced after 1996. Between 1996 and 1999, the number of deaths due to ischaemic heart disease (IHD) increased considerably, while the number of deaths due to atherosclerosis decreased. Considering the magnitude of these changes, any analyses of mortality trends in these periods treating these data as consistent are practically impossible. This also applies to international comparisons of IHD mortality data. AIM: To develop a method of estimating the number of deaths that would approximate the real numbers of deaths due to IHD in Poland in 1991-2005. METHODS: Sets of individual death records from the Central Statistical Office (CSO) and data from the WHO Mortality Database were used. The IHD mortality data documented officially in Poland were obtained using two different coding systems used consistently before and since 1997. IHD mortality was highly consistent in each of these periods. The applied version of the regression model makes use of both these properties. RESULTS: The system of certifying death causes which was used in Poland before 1997 resulted in underestimating the real number of IHD deaths in Poland in 1991 by around 35% compared to the numbers estimated using a more correct system of certifying death causes used after 1997. Approximate relative error of the official number of deaths due to IHD in 1991 in age groups of 45-54, 65-74, 75-84, and > or = 85 years was 30%, 24%, 49% and 67%, respectively, in men, and 27%, 25%, 52% and 72%, respectively, in women. CONCLUSIONS: An increase in the IHD mortality rate in Poland in 1996-1999 noted by CSO was an apparent phenomenon resulting from inaccuracies in coding death causes before 1997. These inaccuracies were mainly related to IHD, atherosclerosis and cerebrovascular disease. Our method enabled correction of the number of deaths between 1991 and 1996, yielding figures much closer to the real ones. Using this method, it is also possible to assess long-term mortality trends, including evaluation of the effectiveness of different methods of treatment and prevention. In particular, it also refers to the use of the IMPACT model to analyse reasons of changes in IHD mortality in Poland.

Trends in heart failure mortality in Poland between 1980 and 2010.

INTRODUCTION:  Data regarding standardized trends in mortality from heart failure (HF) in the general population are limited. OBJECTIVES:  The aim of the study was to evaluate trends in HF mortality in Poland in the years 1980-2010. PATIENTS AND METHODS:  An analysis of a database of mortality records from 1980-2010 based on National Statistics was performed. Mortality trends for HF by age and sex were analyzed by polynomial or linear regression. RESULTS:  Total crude numbers of HF deaths in 1980 were 21,519 and 23,008 for women and men, respectively, whereas, in 2010, there were 23,304 and 19,558. There was a significant change in mortality trends for HF, from a decline during the first phase of the study to an increase during the most recent years, 2005-2010 (P <0.005 for changes of trends for both sexes). The lowest value reached in 2005 constituted 47% and 41% of the baseline for women and men, respectively. These ratios increased to 59% and 52% in 2010. Stratification by age and sex brought similar results, with the exception of the youngest groups, which showed initial increases in the rates for the years 1980-1985. CONCLUSIONS:  There was a significant decline in the rates of HF mortality in the Polish population for both men and women, showing a maximal reduction of about 50% around 2005. However, between 2005 and 2010, a significant increase in the rates of HF mortality was observed (crude difference equaled 12% for women and 11% for men). It is unknown whether this is a temporary or permanent trend, and the issue requires further investigation.

Sudden cardiovascular death rate and ischaemic heart disease death rate changes during the 5-year period of 2003-2008.

BACKGROUND: A decrease in cardiovascular mortality rates, including deaths due to ischaemic heart disease (IHD), has been observed in Poland since mid-1990s, and at the same time a rapid increase in sudden cardiovascular death (SCD) rate was noted. AIM: To evaluate changes in mortality due to SCD, IHD and SCD+IHD that occurred in 2003-2008 in the Polish population aged 25-64 years. METHODS: Individual data from death certificates and demographic data were obtained from the Central Statistical Office and all analyses were performed in the Department of Cardiovascular Disease Epidemiology, Prevention and Health Promotion. SCD was defined as codes I46.1 and R96, and IHD as codes I20-I25 according to the Tenth Revision of the International Classification of Diseases (ICD-10). Calculated mortality rates per 100,000 inhabitants for 5-year age groups were standardised for the European population structure. RESULTS: In 1997-2008, premature mortality due to SCD among adult men and women aged 25-64 years showed only small variations until 2003, and later an upward trend was observed. In 2005-2008, mortality due to SCD increased by 40% among men and 45% among women, but total mortality due to SCD+IHD remained stable. There was no marked variation in the proportion of mortality due to IHD+SCD in total cardiovascular disease (CVD) mortality both in men and in women. The rate of SCD was related to age. A notable finding was the equalisation of mortality rates due to IHD+SCD per 100,000 in nearly all age groups except for the oldest men and women. In the whole adult Polish population, no clear difference in standardised mortality rates could be noted between 2003 and 2008. SCD mortality rate and its proportion in total CVD mortality differed significantly in relation to the region of Poland. SCD mortality rate among men in the Lubusz and Lesser Poland voivodeships decreased by more than 25% (in women only in the Lubusz voivodeship). In the remaining voivodeships, increases in SCD mortality rate were observed (among men, by 171% in the Pomeranian voivodeship, 66% in the Swietokrzyskie voivodeship, and 60% in the Opole voivodeship; among women, by 248% in the Pomeranian voivodeship, 88% in the Silesian voivodeship, and 85% in the Opole voivodeship). No differences in mortality rates due to IHD+SCD in relation to the region of Poland were observed. CONCLUSIONS: IHD mortality rates in the Polish population aged 25-64 years were underestimated in the majority of voivodeships. At the same time, SCD mortality rates were overestimated. These results indicate deficiencies in our medical care system regarding the diagnosis and prevention of sudden deaths, and awareness of symptoms of life-threatening conditions.

Decline in mortality from coronary heart disease in Poland after socioeconomic transformation: modelling study.

OBJECTIVES: To examine how much of the observed rapid decrease in mortality from coronary heart disease in Poland after the political, social, and economic transformation in the early 1990s could be explained by the use of medical and surgical treatments and how much by changes in cardiovascular risk factors. DESIGN: A modelling study. SETTING: Sources of data included controlled trials and meta-analyses, national surveys, and official statistics. PARTICIPANTS: Population of adults aged 25-74 in Poland in 1991-2005. MAIN OUTCOME MEASURES: Number of deaths prevented or postponed in 2005 attributable to specific treatments for coronary heart disease and changes in risk factors. A previously validated epidemiological model for coronary heart disease was used to combine and analyse data on the uptake and effectiveness of specific cardiac treatments and changes in risk factors. The observed fall in deaths from coronary heart disease from 1991 to 2005 was then partitioned among specific treatments and risk factor changes. RESULTS: From 1991 to 2005, the death rate from coronary heart disease in Poland halved, resulting in 26,200 fewer coronary deaths in 2005 in people aged 25-74. About 37% (minimum estimate 13%, maximum estimate 77%) of this decrease was attributable to treatments, including treatments for heart failure (12%), initial treatments for acute coronary syndrome (9%), secondary prevention treatments after myocardial infarction or revascularisation (7%), chronic angina treatments (3%), and other treatments (6%). About 54% of the fall was attributed to changes in risk factors (minimum estimate 41%, maximum estimate 65%), mainly reductions in total cholesterol concentration (39%) and an increase in leisuretime physical activity (10%); however, these were partially offset by increases in body mass index (-4%) and prevalence of diabetes (-2%). Blood pressure fell in women, explaining about 29% of their decrease in mortality, but rose in men generating a negative influence (-8%). About 15% of the observed decrease in mortality was attributable to reduced smoking in men but was negligible in women. CONCLUSIONS: Over half of the recent fall in mortality from coronary heart disease in Poland can be attributed to reductions in major risk factors and about one third to evidence based medical treatments.

An assessment of regression of left ventricular hypertrophy following alcohol ablation of the interventricular septum in patients with hypertrophic cardiomyopathy with left ventricular outflow tract obstruction.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is characterised by asymmetric myocardial hypertrophy, which is most pronounced in the interventricular septum (IVS) and is responsible for the dynamic obstruction of the left ventricular outflow tract (LVOT). Successful alcohol septal ablation (ASA) of the IVS allows to reduce the thickness of the parabasal part of the IVS myocardium and, in most cases, to permanently reduce the gradient in the LVOT. AIM: To assess, using cardiac magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE), the impact of gradient reduction in the LVOT on the type and severity of left ventricular (LV) remodelling. METHODS: The study included 30 patients (aged 56.9 ± 11.9 years) with HOCM and the mean peak gradient (PG) in the LVOT of 123 ± 33 mm Hg who underwent ASA. MRI measurements were performed before and at 6 months after ASA and TTE measurements were performed before, at 3 months and at 6 months after ASA. RESULTS: PG in the LVOT decreased to an average of 52 ± 37 mm Hg (p 〈 0.0001) at 3 months after ASA and to 37 ± 28 mm Hg (p 〈 0.0001) at 6 months after ASA. TTE revealed a decrease in IVS thickness outside the scar following ASA from 23.6 ± 3.5 mm to 19.3 ± 4.0 mm (p 〈 0.0001) and 19.4 ± 0.4 mm (p 〈 0.0001) at 3 and 6 months, respectively. There was also a decrease in lateral wall (PW) thickness from 15.9 ± 3.2 mm to 14.9 ± 2.9 mm (p = 0.046) and 14.16 ± 2.00 (p = 0.0065) at 3 and 6 months, respectively. MRI revealed a decrease in IVS thickness from 23.7 ± 2.8 mm to 18.04 ± 4.00 mm (p = 0.0001) at 6 months following ASA. We observed a regression of the PW hypertrophy from 13.2 ± 3.35 mm to 12.18 ± 2.4 mm (p = 0.0225). There was a decrease in IVS mass from 108.9 ± 20 g to 91.5 ± 29 g (p = 0.0006). There was a trend towards a decreased LV mass and LV mass excluding IVS mass at 6 months. CONCLUSIONS: A significant decrease in PG in the LVOT is associated with a decrease in LV mass and with regression of LV hypertrophy outside the scar after ASA.