Plasma Lp-PLA(2) mass and apoB-lipoproteins that carry Lp-PLA(2) decrease after sodium.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2) ) is a novel cardiovascular risk marker, which is predominantly complexed to apolipoprotein (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium intake may decrease plasma apoB-containing lipoproteins, we tested whether a sodium challenge lowers plasma Lp-PLA(2) mass, as well as the levels of apoB-containing lipoprotein particles carrying Lp-PLA(2) (apoB-Lp-PLA(2) ), employing a newly developed enzyme-linked immunosorbent assay. MATERIALS AND METHODS: In 45 women and 31 men (mean age 44 ± 14 years), plasma Lp-PLA(2) mass (turbidimetric immunoassay), the level of apoB-Lp-PLA(2) , expressed in apoB concentration and lipoproteins were measured in response to a 3-day challenge with 9 g sodium chloride tablets daily. RESULTS: Urinary sodium excretion increased from 165 ± 60 to 321 ± 70 mmol/24 h (P<0.001) after salt loading. Plasma Lp-PLA(2) mass decreased from 618 (493-719) to 588 (465-698) µg/L (P<0.001), and apoB-Lp-PLA(2) decreased from 0.276 (0.200-0.351) to 0.256 (0.189-0.328) g LDL protein/L (P=0.004) in response to the sodium challenge together with decreases in plasma total cholesterol, nonhigh-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B and the total cholesterol/HDL cholesterol ratio (P<0.01 for all). Changes in plasma Lp-PLA(2) mass were correlated positively with changes in total cholesterol, LDL cholesterol and non-HDL cholesterol (r=0.260-0.276, P<0.05 to P<0.02), whereas changes in apoB-Lp-PLA(2) were correlated positively with changes in non-HDL cholesterol and in the total cholesterol/HDL cholesterol ratio (r=0.232-0.385, P<0.05-0.01). CONCLUSION: Both plasma Lp-PLA(2) mass levels and apoB-Lp-PLA(2) decrease in response to a short-term oral sodium challenge.

Statin and fibrate combination does not additionally lower plasma cholesteryl ester transfer in type 2 diabetes mellitus.

BACKGROUND: Plasma cholesteryl ester transfer (CET) from high density lipoproteins (HDL) to very low and low density lipoproteins (VLDL+LDL) may predict (subclinical) atherosclerosis. We tested the extent to which plasma CET and cholesterol esterification (EST) are decreased by statin and fibrate combination therapy compared to statin and fibrate administration alone in type 2 diabetic patients. METHODS: Plasma CET and EST were measured by isotope assays in 14 type 2 diabetic patients, in whom a randomized placebo-controlled crossover study was carried out (8 weeks treatment with simvastatin (40 mg daily), bezafibrate (400 mg daily) and their combination). Plasma CET and EST from diabetic patients were compared with 42 non-diabetic control subjects with similar triglyceride levels. RESULTS: Plasma CET and EST were elevated in diabetic patients at baseline compared to control subjects (p < 0.01), and were correlated positively with non-HDL cholesterol and triglycerides in non-diabetic subjects and in diabetic patients at baseline (p < 0.01). Decreases in CET during combined treatment (p < 0.05) were not greater than the changes during simvastatin and bezafibrate monotherapy (p > 0.20). EST only decreased during bezafibrate therapy (p < 0.05). Changes in CET during treatment were correlated positively with changes in non-HDL cholesterol (p < 0.05) and triglycerides (p < 0.001). Changes in HDL cholesterol were related inversely to changes in CET (p < 0.05). CONCLUSIONS: Diabetes-associated plasma CET elevations are ameliorated by statin and fibrate monotherapy, but combined lipid lowering drug treatment does not additively lower CET. CET lowering likely contributes to HDL cholesterol changes during statin and fibrate administration.

Antioxidant role of plasma carotenoids in bronchopulmonary dysplasia in preterm infants.

OBJECTIVES: Oxidative stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) and consequently, it might be theorized that sufficient antioxidant defenses are needed to prevent BPD. We hypothesized that, except for vitamins E and A, carotenoids may be important in this defense. Carotenoids are present in human milk; however, they are not added to parenteral nutrition, the main food source of preterm infants in the first week of life. AIM: To evaluate prospectively the role of carotenoids in BPD in a cohort of preterm infants. METHODS: The plasma concentrations of F(2alpha)-isoprostane, alpha- and beta-carotene, lycopene, lutein, vitamin A, and the vitamin E/cholesterol ratio were studied at days 1, 3, and 7 in a cohort of 109 preterm infants, of whom 19 had BPD. RESULTS: When comparing the BPD and control group, infants in the BPD group were younger (p<0.001) and beta-carotene (day 7, p<0.01) and vitamin A concentrations were lower (days 3 and 7, p<0.001). Lycopene, lutein, alpha-carotene, vitamin E, and F(2alpha)-isoprostane concentrations did not differ between groups. CONCLUSIONS: Plasma beta-carotene and vitamin A concentrations are lower in BPD infants which may result in a reduction of their antioxidant protection.

Prognostic value of troponin after elective percutaneous coronary intervention: A meta-analysis.

BACKGROUND: Although the prognostic importance of troponin in patients with anacute coronary syndrome is clear, the significance of troponin elevation after elective percutaneous coronary intervention (PCI) is a subject of debate. However, most studies up to now had a small sample size and insufficient events during follow-up. METHODS: Electronic and manual searches were performed of studies reporting on prognosis of troponin after elective PCI. A meta-analysis was done of all suitable studies, with death in follow-up as primary endpoint and the combination of death or nonfatal myocardial infarction in follow-up as secondary endpoint. RESULTS: 20 studies involving 15,581 patients were included. These studies were published between 1998 and 2007. Overall, troponin was elevated after elective PCI in 32.9% of patients. The follow-up period varied between 3 and 67 months (mean 16.3). Increased mortality was significantly associated with troponin elevation after PCI (4.4% vs. 3.3%, P = 0.001; OR 1.35). Furthermore, the combined endpoint of mortality or nonfatal myocardial infarction also occurred more often in patients with post-procedural troponin elevation (8.1% vs. 5.2%, P < 0.001; OR 1.59). CONCLUSIONS: According to this meta-analysis, troponin elevation after elective PCI provides important prognostic information.

Alterations in plasma lecithin:cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: implications for cardiac outcome.

BACKGROUND: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE). METHODS: Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13-1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay. RESULTS: Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r = -0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age- and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31-0.68), p < 0.001 and 7.58 (95% CI, 3.34-17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15-2.19), p = 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65-1.19), p = 0.39), predicted newly manifest MACE. CONCLUSION: In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome.

Plasma lipoprotein-associated phospholipase A2 mass is elevated in STEMI compared to non-STEMI patients but does not discriminate between myocardial infarction and non-cardiac chest pain.

BACKGROUND: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass predicts future cardiovascular events in the non-acute setting. We tested the extent to which Lp-PLA2 is elevated in patients with acute coronary syndrome. METHODS: A total of 231 consecutive patients referred for acute chest pain participated. Of this number, 144 were diagnosed with myocardial infarction (MI; 100 were classified as MI with ST-elevation (STEMI) and 44 as MI without ST-elevation (non-STEMI)). Eighty-seven patients had non-cardiac chest pain. Plasma Lp-PLA2 mass was measured using turbidimetric immunoassay. RESULTS: Lp-PLA2 mass was not different between MI patients and patients with non-cardiac chest pain (231±72 µg/l vs.243±88 µg/l, p=0.29), and did not relate to MI in age- and sex-adjusted logistic regression analysis (odds ratio per SD increment, 0.92 (95% CI, 0.69-1.23), p=0.58). However, Lp-PLA2 mass was elevated in STEMI compared to non-STEMI patients (246±73 vs. 198±58 ng/ml, p<0.001), and independently predicted STEMI (odds ratio, 2.35 (95% CI, 1.46-3.79), p<0.001). Among MI patients maximal creatine kinase was correlated positively with Lp-PLA2 (r=0.183, p=0.034). CONCLUSIONS: In the acute setting, plasma Lp-PLA2 mass is not elevated in MI patients, although Lp-PLA2 mass appears to relate to the severity of myocardial damage.

Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: relationship with lipoprotein response to antiproteinuric treatment.

OBJECTIVE: LDL-receptor deficiency may provide a mechanism which contributes to atherogenic lipoprotein abnormalities in experimental nephrosis and in humans with glomerular proteinuria. The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation. We tested whether plasma PCSK9 is elevated in proteinuric states, and determined relationships of PCSK9 with lipoprotein responses to proteinuria reduction. METHODS: Thirty-nine kidney patients (e-GFR 61 ± 29 mL/min/1.73 m(2), proteinuria 1.9 [0.9-3.3] g/day; 19 on statin treatment) were studied during 2 randomized double-blind 6-week periods on either lisinopril (40 mg/day) and a regular sodium diet (194 ± 49 mmol Na+/day; baseline treatment) or lisinopril plus valsartan (320 mg/day) and a low sodium diet (102 ± 52 mmol Na(+)/day; maximal treatment), and compared to age- and sex-matched controls. Maximal treatment decreased proteinuria to 0.5 [0.3-1.1] g/day (P < 0.001). RESULTS: Plasma PCSK9 was increased at baseline in proteinuric subjects (213 [161-314] vs. 143 [113-190] ug/L in controls, P ≤ 0.001), irrespective of statin use, e-GFR and BMI. PCSK9 correlated with proteinuria at baseline (R = 0.399, P = 0.018) and at maximal antiproteinuric treatment (R = 0.525, P = 0.001), but did not decrease during proteinuria reduction (P = 0.84). Individual changes in total cholesterol (R = 0.365, P = 0.024), non-HDL cholesterol (R = 0.333, P = 0.041), and LDL cholesterol (R = 0.346, P = 0.033) were correlated positively with individual PCSK9 responses. PCSK9 at baseline independently predicted the total/HDL cholesterol ratio response to treatment (P = 0.04). CONCLUSION: Plasma PCSK9 was elevated in proteinuria, predicted lipoprotein responses to proteinuria reduction but remained unchanged after proteinuria reduction. Inhibition of the PCSK9 pathway may provide a novel treatment strategy in proteinuric subjects.

Metabolic effects of high altitude trekking in patients with type 2 diabetes.

OBJECTIVE: Limited information is available regarding the metabolic effects of high altitude trekking in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirteen individuals with type 2 diabetes took part in a 12-day expedition to the summit of Mount Toubkal (altitude, 4,167 m), Morocco, after 6 months of exercise training. Energy expenditure, body weight, blood glucose, fasting insulin, lipids, and HbA(1c) were assessed. RESULTS: Training reduced fasting glucose (-0.7 ± 0.9 mmol/L, P = 0.026) and increased exercise capacity (+0.3 ± 0.3 W/kg, P = 0.005). High altitude trekking decreased fasting insulin concentrations (-3.8 ± 3.2 µU/L, P = 0.04), total cholesterol (-0.7 ± 0.8 mmol/L, P = 0.008), and LDL cholesterol (-0.5 ± 0.6 mmol/L, P = 0.007). CONCLUSIONS: High altitude trekking preceded by exercise training is feasible for patients with type 2 diabetes. It improves blood glucose, lipids, and fasting insulin concentrations, while glucose control is maintained.

Accuracy of handheld blood glucose meters at high altitude.

BACKGROUND: Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs. METHODOLOGY/PRINCIPAL FINDINGS: Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude. CONCLUSION: At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.

Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus.

PURPOSE: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by statin or fibrate administration in patients with diabetes mellitus. METHODS: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination. RESULTS: ApoM was decreased by 7% in response to simvastatin (P<0.05 from baseline and placebo), and remained unchanged during bezafibrate and combined simvastatin+bezafibrate administration. Plasma apoM concentrations correlated positively with apoB-containing lipoprotein measures at baseline and during placebo (P<0.02 to P<0.001), but these relationships were lost during all lipid lowering treatment periods. CONCLUSIONS: This study suggests that, even though plasma apoM is lowered by statins, apoM metabolism is to a considerable extent independent of statin- and fibrate-affected pathways involved in cholesterol homeostasis.