Cardiovascular risk factors and non-invasive assessment of subclinical atherosclerosis in youth.

UNLABELLED: Our understanding of the natural history of atherosclerosis in childhood and its response to cardiovascular (CV) risk factor reduction have been hampered by the lack of a reliable, non-invasive measure of atherosclerosis. Carotid intima media thickness (IMT), a surrogate marker of atherosclerosis in adults, is increased in youth heterozygous for familial hypercholesterolemia (FH) and declines with lipid lowering pharmacotherapy. The age at which vascular changes can be reliably identified using IMT and the influence of CV risk factors beyond FH on IMT remains unclear. OBJECTIVE: To examine the influence of demographic, family history, anthropometric characteristics and traditional CV risk factors on IMT in children 5-16 years of age (mean age 11 year). METHODS: In a cross-sectional study, we assessed IMT in 148 children (51 with elevated low density lipoprotein (LDL)-cholesterol, 44 with overweight and 53 controls). Measures included: family history of premature coronary heart disease (CHD), physical activity, pubertal stage, smoking history, fasting glucose, insulin, lipid profile, apolipoproteins A1 and B, anthropometry, blood pressure and IMT. RESULTS: The groups were similar for age and family history of premature CHD. Compared to controls, average maximum IMT (0.403+/-0.04 vs 0.387+/-0.029) and average mean IMT were elevated in the hyperlipidemia group (p<0.05), but not in the overweight group (max IMT 0.393+/-0.034; p vs control=0.17). Using multiple regression modelling, age, family history of premature CHD and apoliprotein A1 and B predicted 17% of the variability in IMT. No measure of adiposity predicted IMT. CONCLUSION: Age is an important predictor of IMT in youth. Among traditional CV risk factors, dyslipidemia and family history of premature CHD are independent predictors of IMT.

Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage. METHODS: After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972) by use of a central automated randomisation system. Randomisation was stratified by hospital. The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: The median duration of follow-up was 56 (IQR 51-64) months. All randomised patients were included in the efficacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean difference between groups 4.0/2.2 [SD 19.6/12.0] mm Hg). 465 (15.7%) patients experienced the primary outcome in the telmisartan group compared with 504 (17.0%) in the placebo group (hazard ratio 0.92, 95% CI 0.81-1.05, p=0.216). One of the secondary outcomes-a composite of cardiovascular death, myocardial infarction, or stroke-occurred in 384 (13.0%) patients on telmisartan compared with 440 (14.8%) on placebo (0.87, 0.76-1.00, p=0.048 unadjusted; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary outcome). 894 (30.3%) patients receiving telmisartan were hospitalised for a cardiovascular reason, compared with 980 (33.0%) on placebo (relative risk 0.92, 95% CI 0.85-0.99; p=0.025). Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group (639 [21.6%] vs 705 [23.8%]; p=0.055); the most common reason for permanent discontinuation was hypotensive symptoms (29 [0.98%] in the telmisartan group vs 16 [0.54%] in the placebo group). INTERPRETATION: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome of cardiovascular death, myocardial infarction, or stroke. FUNDING: Boehringer Ingelheim.