Arne Svilaas

Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects.

PURPOSE An elevated plasma homocysteine concentration is an independent risk factor for cardiovascular diseases. In this study, we tested the hypothesis that hyperhomocysteinemia induces endothelial dysfunction mediated, at least in part, through nitric oxide-dependent mechanisms and that folic acid supplementation improves endothelial function in hyperhomocysteinemic subjects. SUBJECTS AND METHODS Endothelial function was evaluated in healthy controls and hyperhomocysteinemic subjects by measuring plasma levels of the nitric oxide-derived end products nitrite and nitrate and by assessing vasodilatory responses in the skin microcirculation and forearm vasculature. In the subjects with hyperhomocysteinemia, these measurements were repeated after 6 weeks and 12 months of folic acid supplementation. RESULTS Compared with healthy controls, hyperhomocysteinemic subjects had significantly lower median plasma levels of nitric oxide-derived end products (12.1 microM [range 4.4 to 41.8] versus 24.6 microM [13.6 to 53.2]; P <0.001), a significantly lower endothelium-dependent vasodilatory response to acetylcholine (P <0.01), hyperemic response in the microcirculation (P <0.01), and total forearm blood flow during reactive hyperemia (P = 0.01). There was no significant difference in the endothelium-independent response. Folic acid treatment for 12 months increased the plasma level of nitric oxide-derived end products by 121% (95% confidence interval [CI], 72% to 170%), the vasodilatory response to acetylcholine by 124% (95% CI, 36% to 212%), and the ischemia-mediated hyperemic responses in the microcirculation by 60% (95% CI, 25% to 96%) and in the forearm vasculature by 47% (95% CI, 21% to 73%). CONCLUSIONS Homocysteine appears to induce its atherogenic effect, at least in part, by depressing endothelial function, possibly through nitric oxide-dependent mechanisms. This effect can be reversed by folic acid supplementation.

Lipid treatment goals achieved in patients treated with statin drugs in Norwegian general practice

Statin drug treatment has still not achieved complete acceptance, and titration to recommended target goals is still not used by physicians in Norway.

How well are patients with atherosclerotic disease treated? Secondary prevention in primary care

Objective - To examine changing trends in the field of secondary prevention of atherosclerotic disease in Norwegian general practice. Design - A multipractice survey of consecutive patients with atherosclerotic disease consulting general practitioners in 1994/95 compared with a similar survey in 1996/97. Setting - Primary health care. Subjects - 707 patients attending 31 general practitioners in 1994/95 and 1353 patients attending 63 general practitioners in 1996/97. Main outcome measures - The patients were examined and interviewed for risk factors and pharmacological treatment. Results - In 1994/95, 18% of the patients had been prescribed a lipid-lowering agent as opposed to 55% in the later survey. Consequently, the average level of LDL cholesterol in the 1996/97 population was 19% lower than in the 1994/95 population (3.8 mmol/l vs 4.7 mmol/l), which may imply a marked risk reduction. Aspirin and beta-blockers were prescribed to approximately 50% of the patients in both surveys. Diabetic patients had the same drug prescription rate and lipid profile as non-diabetics. In both surveys, about 25% of the patients were smokers. Conclusion ? Secondary prevention in the majority of patients with atherosclerotic disease though ameliorating is still unsatisfactory. More attention is needed to achieve and sustain treatment goals.