Kristina Jureniene

Associations between apolipoprotein E genotype, diet, body mass index, and serum lipids in Lithuanian adult population.

Background Apolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population. Methodology/Principal Findings A cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25–64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods. Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R2 change, respectively). Conclusions/Significance APOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.

Association between APOE, SCARB1, PPARα polymorphisms and serum lipids in a population of Lithuanian adults

BackgroundDyslipidemia is one of several known risk factors for coronary heart disease, a leading cause of death in Lithuania. Blood lipid levels are influenced by multiple genetic and environmental factors. Epidemiological studies demonstrated the impact of nutrition on lipid levels within the Lithuanian population although the role of genetic factors for dyslipidemias has not yet been studied. The objective of this study was to assess the distribution of the APOE, SCARB1, PPARα genotypes in the Lithuanian adult population and to determine the relationship of these genotypes with dyslipidemia.MethodsA cross-sectional health survey was carried out in a representative random sample of the Lithuanian population aged 25–64 (n=1030). A variety of single-nucleotide polymorphisms (SNPs) of the APOE (rs429358 and rs7412), SCARB1 (rs5888) and PPARα (rs1800206) genes were assessed using real-time polymerase chain reaction. Serum lipids were determined using enzymatic methods.Results/Principal findingsMen and women with the APOE2 genotype had the lowest level of total and low-density lipoprotein cholesterol (LDL-C). Men with the APOE2 genotype had significantly higher levels of triglycerides (TG) than those with the APOE3 genotype. In men, the carriers of the APOE4 genotype had higher odds ratios (OR) of reduced (<1.0 mmol/L) high density lipoprotein cholesterol (HDL-C) levels versus APOE3 carriers (OR=1.98; 95% CI=1.05-3.74). The odds of having elevated (>1.7 mmol/L) TG levels was significantly lower in SCARB1 genotype CT carriers compared to men with the SCARB1 genotype CC (OR=0.50; 95% CI=0.31-0.79). In men, carriers of the PPARα genotype CG had higher OR of elevated TG levels versus carriers of PPARα genotype CC (OR=2.67; 95% CI=1.15-6.16). The odds of having high LDL-C levels were lower in women with the APOE2 genotype as compared to APOE3 genotype carriers (OR=0.35; 95% CI=0.22-0.57).Conclusions/SignificanceOur data suggest a gender difference in the associations between APOE, SCARB1, PPARα genotypes and lipid levels. In men, the APOE4 genotype and PPARα genotype CG were correlated with an atherogenic lipid profile while the SCARB1 genotype CT had an atheroprotective effect. In women, APOE2 carriers had the lowest odds of high LDL-C.

Diverging trends in the incidence and mortality of stroke during the period 1986—2002: A study from the Stroke register in Kaunas, Lithuania

Aims: The aim of the present study was to explore the longitudinal stroke trends in the middle-aged Lithuanian population. Methods: All stroke events in the studied population were ascertained and validated according to the standardized criteria outlined by the WHO MONICA Project. The study included all patients aged 25 to 64 years who experienced a stroke between 1986 and 2002. Results: A flat trend was observed in both the incidence and the attack rates of stroke among men during the 17-year study period, while among women, the incidence of stroke increased by 1.7%/year, and the attack rates by 2.3%/year. The 28-day case fatality and mortality rates of stroke decreased significantly in both sexes. The decline in case fatality explained 100% of the decline in mortality. Among the types of stroke, cerebral infarction contributed most to the decline in the mortality in men. In women, the mortality from cerebral infarction and intracerebral haemorrhage declined similarly to that from all types of strokes. Conclusions: Findings from our study indicating no positive changes in the incidence of stroke but instead an increase among middle-aged women in Kaunas are disturbing. These results suggest a need for the intensification of appropriate strategies for stroke prevention by the public health officials in Lithuania.

Physical, behavioural and genetic predictors of adult hypertension: the findings of the Kaunas Cardiovascular Risk Cohort study.

Background The roots of adult hypertension go back to childhood. This study aimed to examine the independent effects of physical, behavioural and genetic factors identified in childhood and mid-adulthood for prediction of adult hypertension. Methods The study subjects were participants of the Kaunas Cardiovascular Risk Cohort study started in 1977 (n = 1082, age 12–13 years). In 2012, a total of 507 individuals (63.9% of eligible sample) participated in the 35-year follow-up survey. Health examination involved measurements of blood pressure (BP), anthropometric parameters, and interview about health behaviours. Subjects were genotyped for AGT (M235T), ACE (I/D, rs4340), ADM (rs7129220), and CACNB2 (rs12258967) genes polymorphisms. A genetic risk score was calculated as the sum of the number of risk alleles at each of four single nucleotide polymorphisms. Results AGT TT genotype male carriers had the highest mean values of systolic BP in childhood. In females, ADM genotype AA was associated with the highest values of systolic and diastolic BP, while CACNB2 genotype CC carriers had the highest values of diastolic BP in childhood. Systolic and diastolic BP in childhood, gain in BMI from childhood to adulthood, and risky alcohol consumption predicted hypertension in middle-aged men. In women, genetic risk score together with diastolic BP in childhood and gain in BMI were significant predictors of adult hypertension. The comparison of four nested logistic regression models showed that the prediction of hypertension improved significantly after the addition of BMI gain. Genetic risk score had a relatively weak effect on the improvement of the model performance in women. Conclusions BP in childhood and the gain in BMI from childhood to adulthood were significant predictors of adult hypertension in both genders. Genetic risk score in women and risky alcohol consumption in men were independently related with the risk of adult hypertension.

Prognosis of risk factors and trends in mortality from external causes among middle-aged men in Lithuania.

Aims: The aims of this study were to investigate the risk of death and time trends from external causes, and to evaluate the significance of the effects of age, period and birth cohort on suicide mortality among middle-aged men during the period 1971—2000 in Lithuania. Methods: Random samples of men aged 45—59 years from the Kaunas Rotterdam Intervention Study (conducted in 1972—74) and Study of Multifactorial Prevention of CHD (conducted in 1977—80) were examined (n=6,480). The participants of the two surveys were observed until 1 January 2001. Over this time 2,841 men had died, 230 of these from external causes. The Cox proportional hazards model was used to evaluate the risk of death from external causes. Trends in mortality from external causes and average annual changes were based on logarithmic regression analysis. For assessment of the effects of age, period, and birth cohort the Poisson regression model was applied. Results: The risk of mortality from external causes among men was positively related to smoking habits and arterial hypertension and negatively related to education level and total serum cholesterol concentration but there was no association with consumption of alcohol. The risk of suicide mortality was associated with family status and occupation only. Trends in mortality from all external causes showed no significant changes during the period 1971—2000. After adjusting for age and cohort effects, the period effect was statistically significant. Conclusion: Prognosis of risk factors for mortality from external causes and period effect on suicide mortality rates will form important parts of future research agendas.

Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients

BackgroundOvarian cancer is a common gynaecological malignancy still remaining a challenge to treat. The objective of this study was to evaluate the impact of platinum dose reduction and chemotherapy delays on progression free survival and overall survival in patients with stage III ovarian cancer and to analyze reasons for such chemotherapy scheme modifications.MethodsMedical records of patients with FIGO stage III ovarian cancer were reviewed. Inclusion criteria involved FIGO stage III epithelial ovarian carcinoma; cytoreductive surgery performed and 6 courses of platinum-based chemotherapy completed; no neoadjuvant chemotherapy applied; and no history of previous malignancies. Progression free survival and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models.ResultsSignificant 3.3 times higher death risk in patients who experienced only chemotherapy delays compared with patients who did not experience any chemotherapy scheme modifications was established (HR = 3.3, 95% Cl: 1.2 – 8.5, p = 0.016). Increased death risk in patients who experienced only chemotherapy delays compared with patients who experienced both chemotherapy delays and platinum dose reduction was also established (HR = 2.3, 95% Cl: 1.1 – 4.8, p = 0.021). Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, renal disorders, anaemia, poor performance status, gastrointestinal symptoms and neuropathy. Overall survival in patients who experienced chemotherapy scheme modifications with no objective medical reasons was non-inferior than in patients who did not experience any chemotherapy scheme modifications.ConclusionsChemotherapy delays in patients with FIGO stage III ovarian cancer caused lower overall survival. The most common reason for chemotherapy scheme modifications was neutropenia.

All-cause and cardiovascular mortality risk estimation using different definitions of metabolic syndrome in Lithuanian urban population.

OBJECTIVE The objective of the study was to assess mortality risk in the subjects with diagnosed metabolic syndrome (MS) using National Cholesterol Educational Program (NCEP-ATPIII), American Heart Association and National Heart Lung and Blood Institute (AHA/NHLBI) International Diabetes Federation (IDF) and Joint Interim Societies (JIS) definitions. METHODS Two random samples aged 35-64 years were examined in 1992-2002 in the framework within the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study (N=2455). The follow-up was carried out in terms of the end points reached from the baseline health examinations until December 31, 2009. RESULTS Cox regressions demonstrated that MS defined by IDF and JIS definitions remained the only significant determinants for all-cause mortality (RR=1.48 and RR=1.41; p<0.05) and cardiovascular disease (CVD) mortality in men (RR=1.81 and RR=1.66; p<0.05). In men (without previous CVD) the NCEP-ATPIII definition had increased mortality risk from CVD (RR=1.98; p=0.012), than in men with identified MS by the IDF and the new JIS definition. In women the MS was not associated with risk of mortality from CVD. CONCLUSION The MS definitions according to the IDF and JIS criteria appear to be a slightly better predictor of all-cause mortality and mortality from CVD; MS according to the NCEP-ATPIII criteria appears to be a better predictor of mortality from CVD in men.

Cardiovascular risk factors and cognitive function in middle aged and elderly Lithuanian urban population: results from the HAPIEE study

BackgroundThe purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.MethodsData from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.ResultsThe scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR = 2.52; 95% CI = 1.75-3.64; in female OR = 2.45; 95% CI = 1.75, 3.64) as well as ischemic heart disease history (among male OR = 1.28; 95% CI = 1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR = 1.32; 95% CI = 1.03-1.69), poor self-rated health (among male OR = 1.57; 95% CI = 1.15-2.14) and poor quality of life (in male OR = 1.67; 95% CI = 1.07-2.61; in female OR = 2.81; 95% CI = 1.92-4.11) were related to lowered cognitive function.ConclusionsThe findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.

Association between anthropometric indexes and cardiovascular risk factors

The aim of this study was to assess the associations of the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with ischemic heart disease (IHD) and risk factors of IHD in the Lithuanian population aged 25 to 70 years. The cross-sectional health survey was carried out in Kaunas, which is the second largest city in Lithuania, and in five regions randomly selected from the northern, southern, eastern, western and central parts of Lithuania. Data from 2048 subjects (936 men and 1112 women) were analyzed. In both sexes, the odds ratios for reduced high density lipoprotein cholesterol, elevated triglycerides, high fasting blood glucose, and hypertension rose with an increasing quartile of BMI, WC, and WHtR. The likelihood of having IHD was statistically significantly higher in the fourth quartile of these anthropometric measures when compared to the first one. Comparison of the logistic regression models revealed that the models with WHtR best fit the prediction of IHD risk. Compared with BMI and WC, WHtR showed a stronger association with IHD and its risk factors in the Lithuanian adult population.

302PIMPACT OF ANTHRACYCLINE BASED CHEMOTHERAPY INTENSITY ON SURVIVAL OF EARLY BREAST CANCER PATIENTS

ABSTRACT Aim: The relation between chemotherapy dose intensity and patient outcome in the management of early stage breast cancer is still arguable. Randomised trials showed benefit of full standard doses of chemotherapy on schedule. The aim of this study is to assess the impact of chemotherapy dose and intensity related factors on 5-year overall survival in group of early breast cancer (EBC) patients, treated with anthracycline based chemotherapy. Methods: 1826 EBC cases diagnosed and treated in Affiliate of Lithuanian University of Health Sciences Kaunas Oncology Hospital from January 2004 to December 2007 were retrospectively analysed. Inclusion criteria were I – IIIA stage breast cancer and adjuvant anthracycline based chemotherapy. Only 294 patients were included in the analysis. Survival related endpoints were analysed with Kaplan-Meier estimates, long rank tests and Cox proportional hazards models. Results: Patients who have undergone either > 2 cycle-delay (delay at any cycle defined as >3 days vs. plan), or 7 day-delay across the whole chemotherapy systematic plan, or 85%. According to dose and intensity modifications 4 group were analysed: no reductions or delays, reductions only, delays only, both reductions and delays. Our results suggest that shorter survival is related with reductions only, delays only and both delays and reductions as compared to no reductions and delays (p 85%. RDI level HR (95 % CI) p 75% 4.05 (2.430-6.762) 50% 2.61 (1.406-4.837) 0.002 RDI 10.16 (4.872-21.169) Conclusions: Delayed chemotherapy cycles and treatment with insufficient dose of anthracyclines were associated with reduced overall survival in women with early stage breast cancer. Moreover, worse survival is associated with reduced RDI level. Disclosure: All authors have declared no conflicts of interest.