Low level of high density lipoprotein cholesterolin 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

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Background

Purpose

Low level of high density lipoprotein (HDL) cholesterolcan be a critical contributor to elevated riskof coronary heart disease (CHD)in children of patients with premature CHD (PCHD).

To elucidate associations between low HDL-cholesterolin children of patients with PCHD(onset <55 years, men; <60 years, women) with their own and parental characteristics.

Konnov MV et al, 2011

In the framework of the study of risk factorsin families of patients with PCHDwe 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

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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.

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MethodsBMI was calculated as follows: (body mass [kg] / height [m2])

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).

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Definition of Metaabolic Syndrome(*Joint Interim Statement 2009 criteria)

1. Δelevated 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 Hgand/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)

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Statistical methods• Predictors (factors associated with low HDL in children)

were selected by logistical regression analysiswith adjustment for age and sex.

• Before logistical regression for reduction of variabilityof continuous coronary risk factors and to suppresspossible outliers symmetric censoring of 1% of their valueswas carried out;

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Results

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Factors associated with low HDL-cholesterolwere elucidated separately in young (age 5-17, n=148)and adult (age 18-38 years, n=223) children.

Low HDL cholesterol was foundin 47 of 148 (31.8%) children aged 5-17 yearsandin 81 of 223 (36.3%) children aged 18-38 years.

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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

OR 95% CI P

own age, years 0.90 0.81 to 1.01 0.064

own sex, girls vs boys 0.69 0.33 to 1.46 0.333

own triglycerides, mmol/l 2.98 1.28 to 6.94 0.011

own BMI, kg/m2 1.14 1.03 to 1.27 0.015

own waist circumference, cm 1.04 1.00 to 1.09 0.034

own alcohol consumption, yes vs no 0.39 0.14 to 1.09 0.071

low HDL-cholesterol of proband, yes vs no 1.12 0.52 to 2.43 0.773

low HDL-cholesterol of consort, yes vs no 2.46 1.07 to 5.64 0.034

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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

OR 95% CI P

own BMI, tertile 2 (<20.95 kg/m2) vs tertile 1 (≤17.54 kg/m2)

2.43 0.90 to 6.58 0.080

own BMI, tertile 3 (≥20.95 kg/m2) vs tertile 1 (≤17.54 kg/m2)

3.35 1.18 to 9.52 0.023

low HDL-cholesterol of consort, yes vs no 2.46 1.07 to 5.64 0.034

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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 OR 95% CI P

own age, years 0.99 0.93 to 1.05 0.751

own sex, girls vs boys 2.52 1.44 to 4.40 0.001

own waist circumference, cm 1.04 1.02 to 1.07 0.0018

own triglycerides, mmol/l 1.83 1.23 to 2.71 0.0029

low HDL-cholesterol of proband, yes vs no 2.25 2.23 to 4.14 0.0088

low HDL-cholesterol of consort, yes vs no 4.92 2.13 to 11.4 0.0002

metabolic syndrome of consort, yes vs no 3.51 1.61 to 7.65 0.0016

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Table 3b. Children aged 18-38 years (n=223): Characteristics related to low HDL-cholesterol

(n=81, 36.3%) with p<0.1Results of univariate analysis (2)

*additional adjustment for beta-blockers use

Characteristics OR 95% CI P

BMI of consort, kg/m2 1.13 1.04 to 1.22 0.0023

waist circumference of consort, cm 1.04 1.01 to 1.08 0.0061

systolic BP of consort, mm Hg 1.02 1.01 to 1.04 0.0062

*heart rate of consort, beats pro minute 1.02 1.01 to 1.04 0.0062

basal serum glucose of consort, mmol/l 2.02 1.14 to 3.61 0.014

diastolic BP of consort, mm Hg 1.04 1.00 to 1.07 0.034

arterial PreHT/HT of consort, yes vs no 1.58 0.97 to 2.55 0.065

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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

OR 95% CI P

own waist circumference, tertile 2 (<83 cm) vs tertile 1 (≤73 cm)

2.73 1.27 to 5.84 0.0098

own waist circumference, tertile 3 (≥83 cm) vs tertile 1 (≤73 cm)

4.68 2.01 to 10.9 0.0003

own triglycerides, mmol/l 1.56 1.03 to 2.35 0.036

low HDL-cholesterol of proband, yes vs no 2.11 1.16 to 3.83 0.014

metabolic syndrome of consort, yes vs no 4.67 2.02 to 10.8 0.0003

*heart rate of consort, beats pro minute 0.93 0.88 to 0.97 0.0021

*additional adjustment for beta-blockers usie

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Conclusions

Low HDL cholesterol was highly prevalentin this group of different age people

with parental premature CHD.

Independent predictors of low HDL-cholesterolin this sample of children of patients with premature CHD

were mostly metabolic factorsboth own (body mass index, waist circumference,

triglycerides)and parental (low HDL-cholesterol, metabolic syndrome).

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AbstractOBJECTIVE. 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 years OR 95% CI p

own BMI, tertile 3 (≥20.95 kg/m2) vs tertile 1 (≤17.54 kg/m2) 4.68 2.01 to 10.9 0.0003

low HDL-cholesterol of consort, yes vs no 2.46 1.07 to 5.64 0.034

Children aged 18-38 years

own waist circumference, tertile 3 (≥83 cm) vs tertile 1 (≤73 cm) 4.68 2.01 to 10.9 0.0003

own triglycerides, mmol/l 1.56 1.03 to 2.35 0.036

low HDL-cholesterol of proband, yes vs no 2.11 1.16 to 3.83 0.014

metabolic syndrome of consort, yes vs no 4.67 2.02 to 10.8 0.0003

heart rate of consort, beats pro minute 0.93 0.88 to 0.97 0.0021

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

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