Markers of cardiovascular risk and their reversibility with acute oxygen therapy in Kyrgyz highlanders with high altitude pulmonary hypertension.

BACKGROUND: High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. METHODS: We studied 34 HAPH+ and 54 HH at Aksay (3250m), and 34 LL at Bishkek (760m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean±SD 34±3, 22±5, 16±4mmHg, respectively (p<0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG-derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. RESULTS: Pulse oximetry in HAPH+, HH and LL was, mean±SD, 88±4, 92±2 and 95±2%, respectively (p<0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422±24, 405±27, 400±28ms (p<0.05 HAPH+ vs. others); corresponding SI was 10.5±1.9, 8.4±2.6, 8.5±2.0m/s, heart rate was 75±8, 68±8, 70±10 bpm (p<0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. CONCLUSIONS: Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling.

The frequency of familial hypercholesterolemia amongst patients in the outpatient clinic of the tertiary specialized cardiology center in Kyrgyzstan.

BACKGROUND: Familial hypercholesterolemia (FH) is frequently underdiagnosed. Prevalence of the FH in Kyrgyzstan is unknown. AIM: to investigate the prevalence of FH amongst patients in the outpatient settings of the tertiary cardiologic center in Kyrgyzstan. METHODS: Retrospective observational study was conducted using the database of the laboratory of biochemistry and electronic database of outpatient department of the National Center of Cardiology and internal diseases. Patient with the level of total cholesterol (TC) ≥7,5 mmol/l and/or low density lipoprotein cholesterol (LDL-C) ≥ 4,9 mmol/l without signs of secondary hyperlipidemia were included in the analysis. FH was defined using Dutch Lipid Clinic Network criteria. RESULTS: according to the laboratory database levels of TC and LDL-C was conducted in 8281patiens and 525 of them had a high lipid levels. After exclusion of patients with secondary hyperlipidemia, high level of triglycerides and pregnant women - 91 patients were included in the analysis. Among them the definite FH was revealed in 2 (2,2%) patients, probable FH - in 6 (6,6%), and possible in 76 (83,5%), and in 7,7% there were no signs of FH. CONCLUSION: Frequency of potential FH (definite and probable) in our analysis was low. To understand the real prevalence of FH in a Kyrgyz population epidemiological study is needed.

[An Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism of apo C-III gene was determined by PCR method. RESULTS: In examined persons the most frequent was TC genotype as in group with MS as in controls. The difference on genotype's frequency between group was close to significant level (χ2 =5.48; p = 0.06) and odd ratio (OR) for MS between CC and TT carriers was 2.57 (95% CI 1.15-5.72); p = 0.019). Frequency of 455C allele in control group was--0.44 and in group with MS--0.54 (χ2 = 4.55; p = 0.036). In carriers of CC genotype there was noted that the frequency of IR (61.8% vs 23.1% vs 36.3%; p < 0.005), insulin level (11.9 [7.04-16.3] vs 5.73 [3.34-10.3] vs 7.54 [4.59-12.2] µIU/ml; p < 0.01) and HOMA index (3.14 [1.66-4.79] vs 1.46 [0.8-2.6] vs 2.05 [1.12-3.6]; p < 0.01) were significantly higher compared with TT and TC genotypes groups respectively. OR for IR between CC and TT carriers was 5.39 (95% CI 1.7-16.9; p = 0.0028). There also was an association between CC genotype and other MS components such as abdominal obesity (χ2--6.24; p--0.044, OR (95% CI--2.21 [1.03-4.82]) and high level of blood triglycerides (χ2--7.57; p--0.022, OR (95% CI) 2.5 [1.14-5.5]). CONCLUSION: In examined Kyrgyz ethnic population the most frequent was heterozygous TC genotype of T455C polymorphism of apo C-III. An association of 455C allele and CC genotype with MS, IR, abdominal obesity and high level of triglycerides was revealed. Key words: apolipoprotein C-III; T455C gene polymorphism; metabolic syndrome, insulin resistance.

Cerebral oxygenation in highlanders with and without high-altitude pulmonary hypertension.

NEW FINDINGS: What is the central question of this study? Cerebral hypoxia impairs cognitive function and exercise performance and may result in brain damage. Residents at high altitude, in particular those with high-altitude pulmonary hypertension, are prone to hypoxaemia due to the exposure to reduced barometric pressure and impaired pulmonary gas exchange. Whether highlanders have a reduced cerebral oxygenation has not been studied. What is the main finding and its importance? We found that despite a reduced arterial oxygen saturation, healthy highlanders and even those with pulmonary hypertension have a similar cerebral oxygenation to healthy lowlanders, suggesting that compensatory mechanisms protect long-term residents at high altitude from cerebral hypoxia. Abstract High-altitude pulmonary hypertension (HAPH), a chronic altitude-related illness, causes hypoxaemia and impaired exercise performance. We evaluated the hypothesis that haemodynamic limitation and hypoxaemia in patients with HAPH are associated with impaired cerebral tissue oxygenation (CTO) compared with healthy highlanders (HH) and lowlanders (LL). We studied 36 highlanders with HAPH and 54 HH at an altitude of 3250 m, and 34 LL at 760 m. Mean(±SD) pulmonary artery pressures were 34(±3), 22(±5) and 16(±4) mmHg, respectively (P < 0.05, all comparisons). The CTO was monitored by near-infrared spectroscopy along with pulse oximetry (peripheral arterial oxygen saturation, SpO2) during quiet breathing of room air (RA) and oxygen for 20 min each, and during hyperventilation with RA and oxygen, respectively. In HAPH, HH and LL breathing RA, SpO2 was 88(±4), 92(±2) and 95(±2)%, respectively (P < 0.001, all comparisons), and CTO was similar in the three groups, at 68(±3), 68(±4) and 69(±4)%, respectively (n.s., all comparisons). Breathing oxygen increased SpO2 and CTO significantly more in HAPH than in HH and LL. Hyperventilation (RA) did not reduce CTO in HAPH but did in HH and LL; hyperventilation (oxygen) increased CTO in HAPH only. Highlanders with and without HAPH studied at 3250 m had a similar CTO to healthy lowlanders at 760 m even though highlanders were hypoxaemic. The physiological response to hyperoxia and hypocapnia assessed by cerebral near-infrared spectroscopy suggests that healthy highlanders and even highlanders with HAPH effectively maintain an adequate CTO. This adaptation may be of particular relevance because adequate cerebral oxygenation is essential for vital brain functions.

[Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism.

Oxigenación cerebral en habitantes de gran altura con y sin hipertensión pulmonar de altura / Cerebral oxygenation in high altitude inhabitants with and without high altitude pulmonary hypertension

La Hipertensión pulmonar de gran altura (HAPH),una enfermedad crónica relacionada con laaltura, que causa hipoxemia y un deterioro enel rendimiento del ejercicio. Se ha evaluadola hipótesis que, la limitación hemodinámicae hipoxemia en pacientes con (HAPH), estánasociados con un deterioro en la oxigenación deltejido cerebral (CTO), comparados con habitantes...

[The association of leptin with dislipidemia in group of ethnic Kirghiz].

The article deals with results of evaluation of relationship between leptin and lipid indicators in group of ethnic Kirghiz. The sampling included 322 ethnic Kirghiz (145 males and 177 females) aged from 30 to 75 years. To all patients was applied general clinical examination, anthropometric examination (height, body mass, waist circumference, thighs circumference). The body mass index was calculated. The level of glucose (on an empty stomach), lipids spectrum and leptin of blood serum were measured. The average age of patients consisted 57.7 +/- 9.6 years and average level of leptin was 7.8 ng/ml. The patients were allocated to three groups depending of tertile of leptin (< 3; 3.0-5.51; > or = 5.52 ng/ml in males; 9.6; 9.6-16.6; > or = 16.7 ng/ml in females). In patients from upper tertile as compared with patients from lower tertiles are noted high values of triglycerides (p < 0.001), total cholesterol (p < 0.O01), in males and triglycerides (p = 0.02) in females. Leptin correlated with body mass index (in males: r = 0.68, p < 0.01; in females: r = 0.74, p < 0.001), concentration of triglycerides (in males: r = 0.301, p < 0.001; in females: r = 0.194, p < 0.001). Leptin correlated with total cholesterol in males (r = 0.214, p < 0.05) and with cholesterol of lipoproteins of high density in females (r = 0.156, p < 0.05). The level of leptin in group of ethnic Kirghiz is associated with dislipidemia, obesity, including abdominal obesity.

[Association of leptin with obesity and hypertension in an ethnic Kyrgyz group].

AIM: To study an association of the level of leptin, obesity, and hypertension in a group of ethnic Kyrgyz. SUBJECTS AND METHODS: Three hundred and twenty-two Kyrgyz people (145 men and 177 women) who were aged above 30 years and resided in the Kyrgyz Republic were examined. They underwent physical examination involving the collection of complaints and medical history data, objective examination, and anthropometric (height, weight, waist and hip circumference (WC and HC), body mass index (BMI)) and blood pressure (BP) measurements. The persons filled out the Finnish Diabetes Risk Assessment Form including data on vegetable consumption (daily or every other day) and exercise (more or less than 30 min per day). Fasting plasma glucose and serum leptin levels were determined. RESULTS: All the study participants were allocated to 4 groups according the quartile of leptin levels: < 2.2, 2.2-4.2, 4.3-6.34, and > 6.34 ng/ml for men and < 8.05, 8.05-13.4; 13.5-19.09, and > 19.09 ng/ml for women. The persons in the highest leptin quartile were found to have higher BMI, WC, systolic and diastolic BP (SBP and DBP), and blood glucose levels than those in the lowest quartile. Elevated leptin levels were associated with the higher risk of hypertension. Leptin levels correlated with BMI (r = 0.719; p < 0.001 for men and r = 0.74; p < 0.001 for women) and WC (r = 0.684; p < 0.001 for men; and r = 0.649; p < 0.001 for women). There was also a correlation of leptin levels with SBP (r = 0.355; p < 0.001 and r = 0.277; p < 0.001) and DBP (r = 0.426; p < 0.001 and r = 0.228; p < 0.01) in men and women, respectively. CONCLUSION: Leptin levels were associated with obesity and hypertension in the group of ethnic Kyrgyz people.

[An association of the 825 polymorphism of the g protein 3 subunit with obesity in Kyrgyz population].

GOAL: To study an association of G protein (GP) 3 subunit 825 polymorphism with obesity in native Kyrgyzes. MATERIAL AND METHODS: 210 persons: 89 patients (female - 35, male - 54) with obesity (body mass index [BMI] more or equal 30 kg/m2) and 121 apparently healthy controls (38 female, 83 male) with normal BMI. Arterial blood pressure, anthropometric measurement and laboratory tests for blood glucose and lipid parameters were performed in all examined persons. DNA was extracted from blood cells and GP3 subunit 825 polymorphism was determined by PCR method. RESULTS: groups with TT and CT genotypes were combined together because of the rare frequency of TT genotype. Prevalence of + genotypes in group with obesity (0.72) was significantly higher than in controls - 0.52 (odds ratio 2.55, 95% confidence interval [CI] 1.31-4.23; =0.004). Arterial hypertension (45 vs. 31.3%; =0,049) and obesity (51.2 vs. 30%; p<0.01) occurred more often in + genotypes carriers compared with CC homozygotes. A logistic regression model for obesity showed significant effect of 825T allele (relative risk [RR] 2.89, 95% CI 1.25-6.7; =0.013) and irregular intake of vegetables (RR 3.47, 95% CI 1.52-7.94; =0.003) as predictors of obesity development independent of age, sex and physical activity level. In the regression model for arterial hypertension the 825T allele lost its significance after adjustment for obesity. CONCLUSION: GP3 subunit 825 allele in native Kyrgyzes is associated with obesity.

[Association of C677T gene polymorphism of methylenetetrahydrofolate reductase with insulin resistance among Kirghizes].

AIM: To study an association of C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) and insulin resistance (IR) among ethical Kirghizes. METHODS: 132 Kirghiz patients with IR according to HOMA index (n=132) and sex and age matched patients without IR, diabetes mellitus (DM) type 2 or metabolic syndrome (MS) (n=132) were included into this study. Measurements of blood pressure (BP), body mass index, waist and hip circumference, fasting blood sugar, insulin, lipid parameters and C677T gene polymorphism of MTHFR were performed in all patients. RESULTS: Frequency of CT and TT genotypes was significantly higher in patients with IR than in controls (2 - 7.22, p - 0,027, OR - 1.68, 95% confidence interval 1.13-2.5, p=0.027). T677 allele was also associated with obesity, hypertriglyceridemia and low level of high density lipoprotein cholesterol (HDL-C). CONCLUSION: In Kirghizes carriage of T677 allele of MTHFR gene was associated with IR, abdominal obesity, hypertriglyceridemia and low HDL-C level.

[Association of the serum level of apolipoprotein E with coronary artery disease and carotid artery atherosclerosis in Kyrgyz men with dyslipidemia].

AIM: To study an association of the serum level of apolipoprotein E (apo-E) with risk factors for coronary heart disease (CHD), blood lipids and that with CHD and carotid artery (CA) atherosclerotic lesion in Kyrgyz men with dyslipidemia. SUBJECTS AND METHODS: One hundred and three Kyrgyz men, including 48 with CHD and 55 without this disease, were examined. A clinical examination was performed and blood lipid composition and serum glucose and apo-E levels were determined. The diagnosis of CHD was established in accordance with the conventional criteria. Whether atherosclerosis was present was determined by ultrasound duplex scanning. RESULTS: Low serum apo-E concentrations were associated with the presence of obesity, the higher blood levels of glucose and triglycerides. There was no correlation with other lipid metabolic parameters and the presence of CHD. A nonlinear relationship was noted between serum apo-E levels and CA atherosclerotic lesion, which was more frequently observed in patients with the apo-E level in the lower and upper quartiles. CONCLUSION: Low serum apo-E content is a poor factor and associated with obesity, hypertriglyceridemia, elevated serum glucose levels, and the development of CA atherosclerosis.

[Ethnic differences in apolipoprotein B levels in hyperlipidemia in Russian and Kirghiz populations]. / Etnicheskie osobennosti v urovne apolipoproteina B pri giperlipidemiiakh u russkikh i kirgizov.

AIM: To evaluate the levels of apolipoprotein B (apo-B) and coronary heart disease (CHD) risk factors in Russians and the Kirghiz with primary hyperlipidemia (PHL). MATERIAL AND METHODS: Lipid spectrum of the blood (LDLP and HDLP cholesterol, total cholesterol, triglycerides), apo-B, CHD risk factors were studied in 60 Russian and 75 Kirghis patients with PHL aged 28 to 67 years (mean age 50.0 +/- 7.59 years, 56 females and 79 males). RESULTS: In Russians a mean level of LDLP cholesterol and apo-B was significantly higher than in Kirghiz patients (3.95 +/- 1.29 mmol/l vs 3.51 +/- 1.17 mmol/l, p = 0.042; 173.3 +/- 57.3 mg/dl vs 145.5 +/- 49.3 mg/dl, p = 0.003, respectively). CHD in both ethnic groups occurred with similar rates. The multifactorial regression analysis shows that an apo-B concentration can serve an independent risk factor associated with CHD in the Kirghiz population (beta = 0.25, p = 0.03) while in Russians living in Kirghizia this factor is a low content of HDLP cholesterol (beta = -0.25, p = 0.05).

[Painless ischemia in the acute period of myocardial infarct]. / Bezbolevaia ishemiia v ostrom periode infarkta miokarda.

The examination of 119 patients with primary acute macrofocal myocardial infarction included 24-hour monitoring to detect episodes of painful or painless ischemia. Three groups of patients were identified: 55 subjects with both painful and painless ischemia, 39 subjects with painless ischemia and 25 patients without ischemia. Diastolic and systolic functions of the left ventricle were assessed at Doppler echocardiography in all the patients who were followed up for 1 year. It was found that painless ischemia revealed early in myocardial infarction affects negatively left ventricular systolic and diastolic functions thus strongly suggesting an unfavorable short-term prognosis.

[Effects of restoration of coronary circulation on the function of the left ventricle in patients with acute myocardial infarction (a follow-up after 1 year)]. / Vliianie vosstanovleniia koronarnogo krovotoka na funktsiiu levogo zheludochka u bol'nykh ostrym infarktom miokarda (nabliudenie v techenie 1 goda).

Values of overall and local left ventricular function were studied in 89 patients in the acute period and 1 year following myocardial infarction. Three patient groups were identified: (1) 26 patients with coronary artery patency recorded by the first coronary angiography; (2) 20 with coronary blood flow recovery made by thrombolytic therapy; and (3) 40 with coronary occlusion. There was a significant improvement of left ventricular function in the patients from Group 1 during their hospital treatment and 1 year after.

[Thrombolytic reperfusion of coronary arteries and the function of the left ventricle in acute myocardial infarction]. / Tromboliticheskaia reperfuziia koronarnykh arterii i funktsiia levogo zheludochka pri ostrom infarkte miokarda.

Left-ventricular myocardial contractility was assessed in thrombolytically-treated patients with acute myocardial infarction. General and local left-ventricular activity was shown to deteriorate progressively in patients with "late" or altogether absent recovery of coronary flow, whereas patients with early recovery of coronary flow demonstrated intact general contractility parameters and better contractility in the affected area. Coronary reperfusion within 5-6 hours helps to maintain functional capacity, which is less marked than the one in patients with early reperfusion.

[Study of the effect of the restoration of coronary blood flow on left-ventricular contractility in patients with acute myocardial infarction based on the data of computerized two-dimensional echocardiography]. / Vliianie vosstanovleniia koronarnogo krovotoka na sokratitel'nuiu funktsiiu levogo zheludochka u bol'nykh ostrym infarktom miokarda po dannym komp'iuternoi dvukhmernoi ékhokardiografii.

Total and local left-ventricular contractility was assessed by computerized two-dimensional echocardiography in 52 patients with acute myocardial infarction. Three groups of patients were identified: those with recovered coronary flow (group 1), reperfusion failure (group 2) and the lack of occlusion at first coronarography (group 3). Patients from group 3 showed the most intact left-ventricular myocardial contractility and the most favorable clinical course of the disease, while second-group patients had particularly impaired left-ventricular contractility. In the first group, the size of the asynergic area diminished by day 28 of the disease to a greater extent, as compared to the second group. Therefore, coronary reperfusion within the first 6 hours after the attack shows correlation to a smaller asynergic zone and a more favorable clinical course of the disease.