1. Low level of high density lipoprotein cholesterol in children of patients with premature coronary heart disease. Relation to own and parental characteristics. M.V.Konnov*, L.M.Dobordzhginidze, A.D.Deev, N.A.Gratsiansky** Center for Atherosclerosis, Institute Of Physico-Chemical Medicine, Moscow, Russian Federation http://athero.ru*konnov-mihail@yandex.ru, **n.gra@ru.net

2. 2 Background Purpose Low level of high density lipoprotein (HDL) cholesterol can be a critical contributor to elevated risk of coronary heart disease (CHD) in children of patients with premature CHD (PCHD). To elucidate associations between low HDL-cholesterol in children of patients with PCHD (onset <55 years, men; <60 years, women) with their own and parental characteristics. Konnov MV et al, 2011

3. In the framework of the study of risk factors in families of patients with PCHD we examined members of 285 families: - 268 proband-parents (patients with PCHD) aged 32-67 years,70.6% men, 75.7% after MI; - 198 their consorts aged 28-67 years, 18.8% men, 3.7% with overt CHD; - 371 children of proband-parents aged 5-38 years, 56.9% men, without overt CHD. Material Konnov MV et al, 2011

4. 4 Parameters registered alcohol consumption; tobacco smoking; oral contraceptive use; weight; height; body mass index (BMI); waist circumference; heart rate; systolic/diastolic blood pressure (BP); arterial prehypertension (PreHT) and hypertension (HT); total, HDL and low density lipoprotein (LDL) cholesterol; triglycerides; basal serum glucose; impaired glucose tolerance; diabetes mellitus; (in adults) education level and presence of menstruation; metabolic syndrome. Konnov MV et al, 2011

5. 5 Methods BMI was calculated as follows: (body mass [kg] / height [m 2 ]) LDL-cholesterol - calculated with Friedwald‘s formula High BP was defined as arterial prehypertension or hypertension according to criteria of: - 4-th Report of National High BP Education Program Working Group on High BP in children and adolescents criteria (USA) (in persons aged 5-17 years); - 7-th Report of Joint National Committee criteria (USA) (in persons aged ≥18 years). For diagnosis of impaired glucose tolerance and diabetes mellitus were used oral glucose tolerance test (1.75 g of glucose per kg body weight up to a total of 75 g for children/adolescents, 75 g for adults, WHO recommendations, 1998), and ADA criteria (2010). Konnov MV et al, 2011

6. 6 Definition of Metaabolic Syndrome (*Joint Interim Statement 2009 criteria) 1. Δ elevated waist circumference (population and country specific); 2.elevated triglycerides (≥ 1.7 mmol/l) or drug treatment for this lipid abnormality; 3.reduced HDL-cholesterol (< 1.0 mmol/l, men; < 1.3 mmol/l, women) or drug treatment for this lipid abnormality; 4.elevated BP (systolic BP ≥ 130 mm Hg and/or diastolic BP ≥ 85 mm Hg) or antihypertensive drug treatment of previously diagnosed arterial hypertension; 5.elevated fasting plasma glucose (≥ 5.55 mmol/l) or drug treatment of elevated glucose. *clinical identification (diagnosis) of MS – any 3 of 5 criteria. Δ for people of Europid origin (e.g. participants of this study) IDF cut points can be used – waist: ≥ 94 cm (men), ≥ 80 cm (women)

7. 7 Statistical methods Predictors (factors associated with low HDL in children) were selected by logistical regression analysis with adjustment for age and sex. Before logistical regression for reduction of variability of continuous coronary risk factors and to suppress possible outliers symmetric censoring of 1% of their values was carried out; Konnov MV et al, 2011

8. Results 8 Factors associated with low HDL-cholesterol were elucidated separately in young (age 5-17, n=148) and adult (age 18-38 years, n=223) children. Low HDL cholesterol was found in 47 of 148 (31.8%) children aged 5-17 years and in 81 of 223 (36.3%) children aged 18-38 years. Konnov MV et al, 2011

9. 9 Table 1. Children aged 5-17 years (n=148): Characteristics related to low HDL-cholesterol (n=47, 31.8%) with p<0.1. Results of univariate analysis OR, CI, P – odds ratio, confidence interval and P-level,, respectively Characteristics related (with p<0.1) to low HDL-cholesterol (47/148 [31.8%]) in children aged 5-17 years OR95% CIP own age, years0.900.81 to 1.010.064 own sex, girls vs boys0.690.33 to 1.460.333 own triglycerides, mmol/l2.981.28 to 6.940.011 own BMI, kg/m 2 1.141.03 to 1.270.015 own waist circumference, cm1.041.00 to 1.090.034 own alcohol consumption, yes vs no0.390.14 to 1.090.071 low HDL-cholesterol of proband, yes vs no1.120.52 to 2.430.773 low HDL-cholesterol of consort, yes vs no2.461.07 to 5.640.034 Konnov MV et al, 2011

10. 10 Table 2. Independent predictors of low HDL-cholesterol in children aged 5-17 years. Results of multivariate analysis OR, CI, P – odds ratio, confidence interval and P-level,, respectively Independent predictors (with p<0.05) of low HDL-cholesterol (47/148 [31.8%) in children aged 5-17 years OR95% CIP own BMI, tertile 2 (<20.95 kg/m 2 ) vs tertile 1 (≤17.54 kg/m 2 ) 2.430.90 to 6.580.080 own BMI, tertile 3 (≥20.95 kg/m 2 ) vs tertile 1 (≤17.54 kg/m 2 ) 3.351.18 to 9.520.023 low HDL-cholesterol of consort, yes vs no2.461.07 to 5.640.034 Konnov MV et al, 2011

11. 11 Table 3a. Children aged 18-38 years (n=223): Characteristics related to low HDL-cholesterol (n=81, 36.3%) with p<0.1 Results of univariate analysis (1) Characteristics OR95% CIP own age, years0.990.93 to 1.050.751 own sex, girls vs boys2.521.44 to 4.400.001 own waist circumference, cm1.041.02 to 1.070.0018 own triglycerides, mmol/l1.831.23 to 2.710.0029 low HDL-cholesterol of proband, yes vs no2.252.23 to 4.140.0088 low HDL-cholesterol of consort, yes vs no4.922.13 to 11.40.0002 metabolic syndrome of consort, yes vs no3.511.61 to 7.650.0016 Konnov MV et al, 2011

12. 12 Table 3b. Children aged 18-38 years (n=223): Characteristics related to low HDL-cholesterol (n=81, 36.3%) with p<0.1 Results of univariate analysis (2) *additional adjustment for beta-blockers use Characteristics OR95% CIP BMI of consort, kg/m 2 1.131.04 to 1.220.0023 waist circumference of consort, cm1.041.01 to 1.080.0061 systolic BP of consort, mm Hg1.021.01 to 1.040.0062 *heart rate of consort, beats pro minute1.021.01 to 1.040.0062 basal serum glucose of consort, mmol/l2.021.14 to 3.610.014 diastolic BP of consort, mm Hg1.041.00 to 1.070.034 arterial PreHT/HT of consort, yes vs no1.580.97 to 2.550.065 Konnov MV et al, 2011

13. 13 Table 4. Independent predictors of low HDL-cholesterol in children aged 18-38 years. Results of multivariate analysis Independent predictors (with p<0.05) of low HDL-cholesterol (81/223 [36.3%) in children aged 18-38 years OR95% CIP own waist circumference, tertile 2 (<83 cm) vs tertile 1 (≤73 cm) 2.731.27 to 5.840.0098 own waist circumference, tertile 3 (≥83 cm) vs tertile 1 (≤73 cm) 4.682.01 to 10.90.0003 own triglycerides, mmol/l1.561.03 to 2.350.036 low HDL-cholesterol of proband, yes vs no2.111.16 to 3.830.014 metabolic syndrome of consort, yes vs no4.672.02 to 10.80.0003 *heart rate of consort, beats pro minute0.930.88 to 0.970.0021 *additional adjustment for beta-blockers usie Konnov MV et al, 2011

14. 14 Conclusions Low HDL cholesterol was highly prevalent in this group of different age people with parental premature CHD. Independent predictors of low HDL-cholesterol in this sample of children of patients with premature CHD were mostly metabolic factors both own (body mass index, waist circumference, triglycerides) and parental (low HDL-cholesterol, metabolic syndrome). Konnov MV et al, 2011

15. 15 Abstract OBJECTIVE. To elucidate associations between low HDL-C in children of patients with PCHD (onset <55, men; <60 years, women) and their own and parental characteristics. METHODS. We examined members of 285 families: 268 probands (70.6% men, age 32-67 years), their 198 consorts (18.8% men, 28-67 years, 3.7% overt CHD) and 371 their children (56.9% men, age 5-38 years, no overt CHD). We registered alcohol consumption, smoking, oral contraceptive use, height, body mass index (BMI), waist circumference (WC), heart rate (HR), systolic/diastolic BP, total/low density lipoprotein cholesterol, HDL-C, triglycerides (TG), serum glucose, impaired glucose tolerance, diabetes, arterial pre-/hypertension (NHBPEP-4 or JNC-7 criteria depending on age) and (in adults) education, menstruation status, metabolic syndrome (MS, JIS criteria). Low HDL-C was defined as ≤25 percentile (Lipid Research Clinics, 5-17 years), or <1.0 (men), <1.3 (women) mmol/l (adults). Predictors of low HDL-C were selected by sex, age adjusted logistic regression in 2 age groups: 5-17, 18-38 years. RESULTS. Low HDL-C was found in 47/148 (31.8%) children aged 5-17 years. Its independent predictors were own BMI and low HDL-C of consort. Low HDL-C was found in 81/223 (36.3%) adult children. Its predictors were WC and TG of children, low HDL-C of proband, MS and HR of consort (table). Children aged 5-17 yearsOR95% CIp own BMI, tertile 3 (≥20.95 kg/m 2 ) vs tertile 1 (≤17.54 kg/m 2 )4.682.01 to 10.90.0003 low HDL-cholesterol of consort, yes vs no2.461.07 to 5.640.034 Children aged 18-38 years own waist circumference, tertile 3 (≥83 cm) vs tertile 1 (≤73 cm)4.682.01 to 10.90.0003 own triglycerides, mmol/l1.561.03 to 2.350.036 low HDL-cholesterol of proband, yes vs no2.111.16 to 3.830.014 metabolic syndrome of consort, yes vs no4.672.02 to 10.80.0003 heart rate of consort, beats pro minute0.930.88 to 0.970.0021 CONCLUSION. In this group of different age people with parental premature CHD independent predictors of low HDL-cholesterol were mostly own (body mass index, waist circumference, triglycerides) and parental (low HDL- cholesterol, metabolic syndrome) metabolic factors. Independent predictors of low HDL-cholesterol Konnov MV et al, 2011