Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease.

BACKGROUND: Although reduced intracellular levels of magnesium have been described in patients with acute myocardial infarction, its significance as a regulator of thrombosis remains unknown. METHODS AND RESULTS: To determine whether reduced intracellular levels of magnesium enhance platelet-dependent thrombosis, we evaluated 42 patients with coronary artery disease (CAD) by exposing porcine aortic media to their flowing unanticoagulated venous blood for 5 minutes by using an ex vivo perfusion (Badimon) chamber. Baseline analysis demonstrated significant associations between intracellular levels of magnesium, platelet-dependent thrombosis (P =.02), and platelet P-selectin (CD62P) expression (P <.05). Patients were divided into 2 groups: below (n = 22) and above (n = 20) the median intracellular levels of magnesium (1.12 microg/mg protein). There were no significant differences in age, body mass index, serum lipids, fibrinogen, platelet count, or serum magnesium levels between the two groups. Platelet-dependent thrombosis was significantly higher in patients with intracellular levels of magnesium below compared with above median (150 +/- 128 vs 45 +/- 28 microm(2)/mm, P <.004). Neither platelet aggregation nor CD62P expression was significantly different between the two groups. CONCLUSIONS: Platelet-dependent thrombosis was significantly increased in patients with stable CAD with low intracellular levels of magnesium, suggesting a potential role for magnesium supplementation in CAD.

Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease.

OBJECTIVES: To investigate the influence of blood glucose on platelet-dependent thrombosis (PDT). BACKGROUND: Elevated blood glucose is a predictor of adverse cardiovascular risk independent of a diagnosis of diabetes, possibly due to adverse effects promoting thrombosis. The effects of blood glucose on PDT have not been characterized. METHODS: An ex vivo extracorporeal perfusion protocol was used to measure PDT in 42 patients with stable coronary artery disease (CAD). The Badimon chamber was perfused with unanticoagulated venous blood and PDT evaluated using computerized morphometry. Whole blood impedance aggregometry and flow cytometry evaluated platelet aggregation and P-selectin expression, respectively. RESULTS: Using a multivariate stepwise regression model, blood glucose was the best independent predictor of PDT (R2 = 0.19, p < 0.008), followed by apolipoprotein B (R2 = 0.18, p = 0.002) and intracellular magnesium levels (R2 = 0.12, p = 0.02). Platelet-dependent thrombosis was significantly greater in patients with blood glucose >, compared with <, the median value of 4.9 mmol/l (159 +/- 141 vs. 67 +/- 69 microm2/mm, p < 0.01). Neither platelet aggregation nor P-selectin expression was significantly different between the two groups. Insulin levels correlated with blood glucose (r = 0.56, p = 0.0003), but were not independently associated with either PDT, platelet aggregation or P-selectin expression. A two-way analysis of variance demonstrated an interaction between insulin (>126 pmol/l) and blood glucose (>4.9 mmol/l) in modulating PDT (F [1,38] = 8.5, p < 0.006). CONCLUSIONS: Blood glucose is an independent predictor of PDT in stable CAD patients. The relationship is evident even in the range of blood glucose levels considered normal, indicating that the risk associated with blood glucose may be continuous and graded. These findings suggest that the increased CAD risk associated with elevated blood glucose may be, in part, related to enhanced platelet-mediated thrombogenesis.

Plasma apolipoprotein B levels predict platelet-dependent thrombosis in patients with coronary artery disease.

Elevated plasma apolipoprotein B is a known risk factor for atherosclerotic coronary artery disease (CAD), however its relationship to arterial thrombosis is unexplored. We prospectively assessed apolipoprotein B and platelet-dependent thrombosis (PDT) in 42 CAD patients (37 men, 5 women, mean age 68 +/- 9 years), by exposing porcine aortic media to their flowing unanticoagulated venous blood for 5 min using an ex vivo perfusion (Badimon) chamber. PDT was significantly correlated with apolipoprotein B (r = 0.41, p = 0.009), intracellular magnesium levels (r = -0.46, p = 0.003) fasting blood glucose (r = 0.47, p = 0.002), and total cholesterol (r = 0.43, p = 0.006). PDT did not correlate with serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I or fibrinogen levels. These findings suggest that the positive relationship of elevated apolipoprotein B to CAD may be, in part, related to its prothrombotic effects.

Intracellular magnesium predicts functional capacity in patients with coronary artery disease.

To determine whether increased intracellular levels of magnesium ([Mg]i) are associated with enhanced functional capacity, we performed symptom-limited exercise treadmill testing on 42 stable coronary artery disease (CAD) patients (37 men, 5 women, mean age 68 +/- 9 years). [Mg]i was found to be an independent and significant predictor of exercise duration (R = 0.31, p = 0.02) in a multivariate stepwise regression model. Patients with > normal [Mg]i of 1.23 microg/mg protein (n = 13) had a significantly greater mean functional capacity, measured in higher achieved metabolic equivalents (10.6 +/- 2.5 vs. 8.9 +/- 2.3, p < 0.05) and exercise duration (9.4 +/- 2.3 vs. 7.9 +/- 2.2 min, p < 0.05) compared to patients with [Mg]i

Safety of medically supervised exercise in a cardiac rehabilitation center.

Medically supervised exercise continues to have a low major cardiovascular complication rate. Direct gym supervision by a physician does not appear necessary for safety. The currently proposed cardiac rehabilitation risk stratification criteria do not appear to identify patients at risk for these major complications. The safety of exercise programs with less supervision and electrocardiographic telemetry monitoring is unknown.