Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response

Hypertension is a known risk factor for cardiovascular disease. Hypertensive individuals show exaggerated norepinephrine (NE) reactivity to stress. Norepinephrine is a known lipolytic factor. It is unclear if, in hypertensive individuals, stress-induced increases in NE are linked with the elevations in stress-induced circulating lipid levels. Such a mechanism could have implications for atherosclerotic plaque formation. In a cross-sectional, quasi-experimentally controlled study, 22 hypertensive and 23 normotensive men (mean +/- SEM, 45 +/- 3 years) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma NE and the plasma lipid profile (total cholesterol [TC], low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol, and triglycerides) immediately before and after stress and at 20 and 60 minutes of recovery. All lipid levels were corrected for stress hemoconcentration. Compared with normotensives, hypertensives had greater TC (P = .030) and LDL-C (P = .037) stress responses. Independent of each other, mean arterial pressure (MAP) upon screening and immediate increase in NE predicted immediate stress change in TC (MAP: beta = .41, P = .003; NE: beta = .35, P = .010) and LDL-C (MAP: beta = .32, P = .024; NE: beta = .38, P = .008). Mean arterial pressure alone predicted triglycerides stress change (beta = .32, P = .043) independent of NE stress change, age, and BMI. The MAP-by-NE interaction independently predicted immediate stress change of high-density-lipoprotein cholesterol (beta = -.58, P < .001) and of LDL-C (beta = -.25, P < .08). We conclude that MAP and NE stress reactivity may elicit proatherogenic changes of plasma lipids in response to acute psychosocial stress, providing one mechanism by which stress might increase cardiovascular risk in hypertension.

Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias

We compared atorvastatin with simvastatin-based therapies in a prospective observational study of 201 patients with severe hyperlipidaemia. Atorvastatin 10 mg therapy was substituted for simvastatin 20 mg, 20 mg for 40 mg, 40 mg for simvastatin 40 mg plus resin, and 80 mg for simvastatin-fibrate-resin therapy. Lipid and safety profiles were assessed. Atorvastatin reduced total cholesterol by 31 +/- 11-40 +/- 14% vs. 25 +/- 12-31 +/- 11%; LDL by 38 +/- 16-45 +/- 18% vs. 31 +/- 18-39 +/- 18% and geometric mean triglycerides by 29.3-37.3% vs. 16.6-24.8%, but reduced HDL 11% +/- 47% at 80 mg compared with a 16% +/- 34% increase with simvastatin-based therapy. Target LDL < 3.5 mmol/l was achieved more often with atorvastatin (63% vs. 50%; p < 0.001). Atorvastatin increased geometric mean fibrinogen by 12-20% vs. a 0-6% fall with simvastatin (p << 0.001). Side effects were noted in 10-36% of patients, including one case of rhabdomyolysis, and 36% discontinued therapy. These data suggest that atorvastatin is more effective than current simvastatin-based therapies in achieving treatment targets in patients with familial hypercholesterolaemia but at the expense of a possible increase in side-effects. This issue needs further study in randomized controlled trials.

Dynamics of lipoprotein metabolism in adult growth hormone deficiency

Dyslipidaemia is often associated with adult growth hormone (GH) deficiency. Reduced removal of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apo B-100) can, in part, explain the "unfavourable" lipid profile of these patients. By modifying VLDL composition and through its action on low-density lipoprotein (LDL) receptors, GH may improve the lipid profile by increasing direct hepatic uptake of VLDL apo B-100, thereby decreasing conversion to LDL. Although GH stimulates VLDL apo B-100 secretion, this is exceeded by its effects in upregulating LDL receptors and modifying VLDL composition. We hypothesize that the improved lipid profile, in particular the decrease in cholesterol-rich VLDL particles, may contribute to a possible antiatherogenic action of GH. GH appears to have an important role in hepatic apo B-100 metabolism. However, we are just at the beginning of understanding the underlying mechanism. Further studies are required to investigate the effect of GH on other lipoprotein classes, in particular VLDL subfractions, intermediate-density lipoprotein, LDL and high-density lipoprotein. The key question, however, remains as to whether GH replacement therapy can reduce cardiovascular mortality. Long-term studies with sufficient numbers of patients are required to answer this question.