Low HDL: associated with subclinical atherosclerosis in early childhood

A low plasma level of high-density lipoprotein (HDL) cholesterol was independently associated with increased arterial wall thickness, a marker for subclinical atherosclerosis, according to a study reported by Atherosclerosis Thrombosis & Vascular Biology. In addition, higher levels of blood pressure and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of production of nitric oxide, which is important in maintaining arterial endothelial integrity and inhibiting platelet aggregation, leukocyte adhesion and smooth muscle proliferation, were associated with greater arterial wall thickness. These data suggest that mechanisms that alter arterial structure are present at a very early age. The report was reviewed by HDL Forum Editor Professor Philip Barter.

 

Ayer JG, Harmer JA, Nakhla S et al. HDL-cholesterol. Blood pressure and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children. Arterioscler Thromb Vasc Biol 2009;29:943-9.

 

Atherosclerosis is a dynamic disease process, characterised by remodelling of the arterial wall, which progresses over many years before eventually manifesting as clinical vascular disease.  Data from a number of population studies (1-3) have shown that measurement of carotid intima-media thickness (CIMT) is a valid early marker of atherosclerosis, and can be used as a surrogate endpoint for cardiovascular disease in adults. However, the factors that influence CIMT in healthy children have not yet been established. The aim of this report therefore was to explore the effects of different cardiovascular risk factors, as well as markers of inflammation and endothelial dysfunction, on CIMT in early childhood (<10 years of age).

 

This cross-sectional study included data from 405 children (mean age 8.0 years, 51% boys) who had been enrolled before birth in the Childhood Asthma Prevention Study (CAPS). CAPS was a randomized, controlled trial which compared the effects of house dust mite avoidance and omega-3 fatty acid supplementation (from birth to 5 years) on asthma and allergic disease in at-risk children. None of the subjects had type 1 diabetes. Subjects underwent final assessment at age 8 years, three years after the end of the intervention period. Families were also invited to participate at this time.

 

Variables measured in the study included:

- anthropometric data (height, weight, waist and hip circumference and body mass index)

- systolic and diastolic blood pressure

- lipids (total, non-HDL and HDL cholesterol and triglycerides) and apolipprotein A-I (apoA-I)

- ADMA and symmetric dimethylarginine (SDMA), its stereoisomer.

- hs-C-reactive protein (hs-CRP)

History of premature coronary heart disease (before the age of 55 years) in the child’s parents and grandparents was noted. The level of physical activity in the children was rated using a 3-point scale (0-1 hours, 2-3 hours or >3 hours per day).

 

CIMT was measured in the left and right carotid arteries using a portable ultrasound system, and the average of six measurements was used in the analysis.

 

CIMT was shown to be positively associated with ADMA (p=0.001) and systolic blood pressure (p<0.001) and inversely associated with HDL cholesterol (p=0.02). ApoA-I was also inversely associated with CIMT, although the correlation was not statistically significant (p=0.07). The significant association of HDL cholesterol, ADMA and systolic blood pressure with CIMT remained after multivariate analysis (Table 1).  

 The authors concluded that their findings suggest an important role for HDL cholesterol, endothelial function and blood pressure in early arterial structural changes that may lead to atherosclerosis. The association of lower HDL cholesterol with higher CIMT is consistent with data in young adults (4) and may relate to the action of HDL in promoting reverse cholesterol transport. However, given the relative paucity of lipid in the arterial wall at this age, it may be likely that potential anti-inflammatory and anti-oxidant effects of HDL on the arterial wall may be more important in preventing preclinical atherosclerotic changes at a very early age. References1. Chambless LE, Heiss G, Folsom AR et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol 1997; 146: 483-94.2. Salonen JT, Salonen R. Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation 1993; 87: II56-II65.3. O’Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999; 340: 14-22.4. Urbina EM, Srinivasan SR, Tang R et al. Impact of multiple coronary risk factors on the intima-media thickness of different segments of carotid artery in healthy young adults. (The Bogalusa Heart Study). Am J Cardiol 2002;90:953-8.


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