Zita Ausrele Kucinskiene

Increased Plasma 7β-Hydroxycholesterol Concentrations in a Population With a High Risk for Cardiovascular Disease

The mortality in coronary heart disease among 50- to 54-year-old men is 4 times higher in Lithuania than in Sweden. It was recently suggested that traditional risk factors could not explain this mortality difference. LDL of Lithuanian men showed, however, a lower resistance to oxidation than that of Swedish men. In addition, the plasma concentration of gamma-tocopherol, lycopene, and beta-carotene were lower in Lithuanian men. In the present investigation, we determined plasma oxysterols in men from Lithuania and Sweden and found that the plasma concentration of 7 beta-hydroxycholesterol was higher in Lithuanian men, 12+/-5 versus 9+/-8 (SD) ng/mL (P=0.0011). This oxysterol is a cholesterol autoxidation product and there is no indication that it should have an enzymatic origin. Mean LDL oxidation lag time was shorter in Lithuanian men (75+/-14 versus 90+/-13 minutes, P<0.0001) and the concentration of LDL linoleic acid was lower (249+/-56 versus 292+/-54 microgram/mg of LDL protein, P<0.0001). Lipid corrected gamma-tocopherol was 0.07+/-0.02 mg/mL in Vilnius men and 0.12+/-0. 04 mg/mL (P<0.0001) in Linköping men. There was a negative correlation between the concentration of 7 beta-hydroxycholesterol and lag time (R=-0.31, P=0.0023). It is suggested that the higher 7 beta-hydroxycholesterol concentration in Lithuanian men is an indication of an increased in vivo lipid peroxidation.

Increased psychosocial strain in Lithuanian versus Swedish men: the LiVicordia study.

Objective Coronary heart disease (CHD) mortality is four times higher in 50-year-old Lithuanian men than in 50-year-old Swedish men. The difference cannot be explained by standard risk factors. The objective of this study was to examine differences in psychosocial risk factors for CHD in the two countries. Methods The LiVicordia study is a cross-sectional survey comparing 150 randomly selected 50-year-old men in each of the two cities: Vilnius, Lithuania, and Linkoping, Sweden. As part of the study, a broad range of psychosocial characteristics, known to predict CHD, were investigated. Results In the men from Vilnius compared with those from Linkoping, we found a cluster of psychosocial risk factors for CHD; higher job strain (p <.01), lower social support at work, lower emotional support, and lower social integration (p values <.001). Vilnius men also showed lower coping, self-esteem, and sense of coherence (p values < .001), higher vital exhaustion, and depression (p values < .001). Quality of life and perceived health were lower and expectations of ill health within 5 to 10 years were higher in Vilnius men (p values < .001). Correlations between measurements on traditional and psychosocial risk factors were few and weak. Conclusions The Vilnius men, representing the population with a four-fold higher CHD mortality, had unfavorable characteristics on a cluster of psychosocial risk factors for CHD in comparison with the Linkoping men. We suggest that this finding may provide a basis for possible new explanations of the differences in CHD mortality between Lithuania and Sweden.

Genetic characterization of northeastern Italian population isolates in the context of broader European genetic diversity

Population genetic studies on European populations have highlighted Italy as one of genetically most diverse regions. This is possibly due to the country’s complex demographic history and large variability in terrain throughout the territory. This is the reason why Italy is enriched for population isolates, Sardinia being the best-known example. As the population isolates have a great potential in disease-causing genetic variants identification, we aimed to genetically characterize a region from northeastern Italy, which is known for isolated communities. Total of 1310 samples, collected from six geographically isolated villages, were genotyped at >145 000 single-nucleotide polymorphism positions. Newly genotyped data were analyzed jointly with the available genome-wide data sets of individuals of European descent, including several population isolates. Despite the linguistic differences and geographical isolation the village populations still show the greatest genetic similarity to other Italian samples. The genetic isolation and small effective population size of the village populations is manifested by higher levels of genomic homozygosity and elevated linkage disequilibrium. These estimates become even more striking when the detected substructure is taken into account. The observed level of genetic isolation in Friuli-Venezia Giulia region is more extreme according to several measures of isolation compared with Sardinians, French Basques and northern Finns, thus proving the status of an isolate.

Risk factors for coronary heart disease in different socioeconomic groups of Lithuania and Sweden : the LiVicordia study

Aims: Lithuanian middle-aged men have a fourfold higher risk for coronary heart disease (CHD) mortality compared with Swedish men. In Sweden, CHD mortality is twice as high in blue- compared with white-collar workers. Whether the same risk factors that characterized Lithuanian men, compared with Swedish men, could be found in low socioeconomic groups within the cities was investigated. Methods : The LiVicordia study compared both traditional and new possible risk factors for CHD among 150 50-year-old men in Linköping, Sweden and Vilnius, Lithuania. A comparison was made of the prevalence of these risk factors in high and low socioeconomic groups within the cities and, after controlling for the city, variations across socioeconomic groups in the total sample. Results: Small differences were found in traditional risk factors between cities. However, Vilnius men were shorter, had lower serum levels of antioxidant vitamins, more psychosocial strain, and lower cortisol response to a standardized laboratory stress test. These characteristics were also found among men in low social classes in both cities. In linear regression models, short stature, low serum β-carotene, low social integration, coping and self-esteem, high vital exhaustion, high baseline and low cortisol response to stress were related to low social class. Conclusions: The same set of risk factors, mainly relating to oxidative and psychosocial stress, that characterized Vilnius men was also found in men in low social classes within the cities. The results suggest that a common set of risk factors may help to explain health differences both between and within countries.

Lower serum levels of beta-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine : The LiVicordia study.

OBJECTIVE In 1995, middle-aged Lithuanian men had a four-fold higher risk than Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia study had reported significantly lower levels of the lipid-soluble antioxidants lycopene, beta-carotene, and gamma-tocopherol among Lithuanian men than among Swedish men. We examined whether there were differences in urinary 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups of men. METHODS Using automated coupled column high-performance liquid chromatography with electrochemical detection, we examined 50-y-old men randomly sampled from Linköping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with regard to urinary concentrations of 8-OHdG. RESULTS Levels of 8-OHdG were higher in the Lithuanian men than in the Swedish men (20.9 +/- 0.91 versus 14.9 +/- 0.75 nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non-smokers (P < 0.001). Serum levels of alpha- and beta-carotene were inversely correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking and low levels of beta-carotene contributed significantly to higher oxidative DNA damage expressed as urinary 8-OHdG. CONCLUSIONS These findings indicate that increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in Lithuanian men. They supported previous suggestions that increased oxidative stress may be one factor behind the higher mortality in Lithuanian men.

Long chain polyunsaturated fatty acids may account for higher low-density lipoprotein oxidation susceptibility in Lithuanian compared to Swedish men

Objectives: Mortality in coronary heart disease among middle-aged men is four times higher in Lithuania than in Sweden. Traditional risk factors cannot account for this difference. We earlier reported that low-density lipoprotein (LDL) in Lithuanian men showed a lower resistance to oxidation, measured as LDL lag time during copper oxidation, than that in Swedish men. Serum concentrations of several fat-soluble antioxidant vitamins were lower among Lithuanian men. The aim of this study was to investigate whether differences in LDL fatty acid composition could account for the difference in LDL oxidation susceptibility between men in the two countries. Methods: This cross-sectional study included randomly selected healthy 50-year-old men from Vilnius, Lithuania (n = 50) and Linköping, Sweden (n = 50). Main outcome measures were fatty acids in LDL, phospholipid (PL) and cholesterol ester (CE) fractions of LDL and LDL oxidation susceptibility. Results: The mean proportions of PL 20:5n3 (eicosapentaenoic acid, EPA) were higher in Vilnius men (2.09 - 1.05 vs. 1.53 - 0.58%, p = 0.004). LDL lag time was shorter in Vilnius men, mean - SD (75.4 - 13.6 vs. 89.5 - 13.1 mins, p < 0.0001) than in Linköping men. Mean serum n -tocopherol was lower in Vilnius men (0.07 - 0.05 vs. 0.12 - 0.04 w g/mmol, p < 0.0001) but f -tocopherol did not differ. In a multiple regression analysis controlled for city, high PL-EPA, low alpha-tocopherol, and high plasma triglycerides significantly contributed to a short LDL lag time, r 2 = 0.53. Conclusions: Fat quality, i.e. poly unsaturated fatty acids, especially LDL-EPA, plasma triglycerides and antioxidative vitamins may partly account for the increased LDL oxidation susceptibility found in Vilnius men compared with Linköping men.

Adipose tissue fatty acids in men from two populations with different cardiovascular risk - the LiVicordia study.

The LiVicordia study was set up to investigate possible causes for coronary heart disease mortality in middle-aged Lithuanian men being four times higher than in Swedish men. In a previous part of this study we found lower total and low density lipoprotein (LDL) cholesterol in the Lithuanian men in spite of them having a higher fat intake than in the Swedish men. Their LDL was also more susceptible to oxidation in vitro than was that of the Swedish men. Fat quality can influence LDL oxidation. In order to obtain data on long-term fat quality intake we measured the fatty acid composition of abdominal wall adipose tissue by gas chromatography in men aged 50 years from Vilnius, Lithuania (n=50) and Linköping, Sweden (n=50). Men from Vilnius had a significantly higher percentage of adipose tissue long chain polyunsaturated fatty acids (PUFA) (20:4n6, 20:5n3, 22:5n5, 22:6n3) and lower percentage of saturated fatty acids, especially myristic acid (14:0), 3.4+/-0.7 versus 4.6+/-0.8, p<0.0001. The percentage content of adipose tissue linoleic acid (18:2n6) was 11.5+/-2.1 versus 11.0+/-1.4 (n.s.) and of linolenic acid (18:3n3) 0.7+/-0.3 versus 0.6+/-0.2 (n.s.) in men from Vilnius and Linköping, respectively. It is concluded that the adipose tissue content of essential fatty acids is similar in men from Vilnius and men from Linköping and therefore the intake is also likely to be similar. The higher contents of long chain highly unsaturated fatty acids in men from Vilnius may be of importance in the oxidation process of LDL.

Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men: the LiVicordia study

Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and beta-carotene (inversely) significantly contributed to a high total ultrasound score (r2 = 0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.