Apolipoproteins B and AI and the risk of ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease.

BACKGROUND AND PURPOSE: The role of blood lipids and lipoprotein-related variables in the prediction of ischemic stroke is less clear than that for coronary heart disease. Apolipoprotein B (Apo B), which reflects the concentration of potentially atherogenic lipoprotein particles, and apolipoprotein AI (Apo A-I), which reflects the corresponding concentration of the anti-atherogenic HDL, represent additional lipoprotein-related variables that may indicate vascular risk. We examined the association between serum concentrations of Apo B, Apo A-I, and the Apo A-I/Apo B ratio and the risk of incident ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease. METHODS: Patients with documented chronic coronary heart disease and measured Apo B and Apo A-I concentration, screened for but not included in a clinical trial of lipid modification were followed over 4.8 to 8.1 years for hospitalized incident cerebrovascular events. RESULTS: Among 3,434 patients 266 (7.7%) developed an incident ischemic cerebrovascular event. Adjusting for potential confounders, the hazard ratios (HR) for incident ischemic cerebrovascular events associated with the top versus bottom quartile of Apo B was 1.68 (95%CI, 1.18-2.40), of Apo A-I 0.71 (95%CI, 0.50-1.00), and of Apo A-I/Apo B ratio 0.51 (95%CI, 0.35-0.74). CONCLUSIONS: These findings support the hypothesis that Apo B, Apo A-I and the Apo A-I/Apo B ratio predict incident ischemic stroke among patients with preexisting atherothrombotic disease. The potential clinical role of measuring these apolipoproteins for ischemic stroke prediction warrants further study.

Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry.

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.

Plasma serotonin response to carbohydrate-rich food in chronic schizophrenic patients: clozapine versus classic antipsychotic agents.

Researchers have reported a stimulatory effect of carbohydrate-rich intake on platelet-poor plasma (PPP) serotonin (5-HT) levels in healthy human subjects. Dietary manipulation may serve as a safer and less invasive means than pharmacologic challenge to provoke serotonergic responsivity in studies of schizophrenia. In the present study, we used the carbohydrate-rich meal test as an indicator of 5-HT activity in 12 patients with chronic schizophrenia maintained for at least 6 months on clozapine. PPP 5-HT levels were measured at baseline and at 1, 2 and 3 h after administration of the test. Findings were compared with those in schizophrenic patients treated with classic antipsychotic agents for the same duration. The maximal PPP 5-HT response was reached 120 min after meal administration in the clozapine-treated group and 60 min after in the classic antipsychotic-treated group (P<0.05 vs baseline for both). The 5-HT level (as percentage of baseline) at 60 min was significantly lower in the clozapine-treated group (P<0.02), as were individual PPP 5-HT peak values (P<0.05). The individual time to reach the peak response was similar in the two groups. Our results indicate that in patients with chronic schizophrenia 5-HT responsivity to the natural challenge of carbohydrate-rich meals is lower in those treated with clozapine than in those given classic antipsychotic agents. Values in both groups were lower than those in an appropriate historical comparative group of healthy subjects. We suggest that both clozapine and classic antipsychotic agents suppress serotonergic system sensitivity, but to a different degree. Copyright 2001 John Wiley & Sons, Ltd.