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. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Plasma Lp-PLA2 mass and apoB-lipoproteins that carry Lp-PLA2 decrease after sodium

Eur J Clin Invest 2012; 42 (11): 12351243 Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2 mass, as well as the levels of apoB-containing lipoprotein particles carrying Lp-PLA2 (apoB-Lp-PLA2), employing a newly developed enzyme-linked immunosorbent assay. Materials and methods In 45 women and 31 men (mean age 44 +/- 14 years), plasma Lp-PLA2 mass (turbidimetric immunoassay), the level of apoB-Lp-PLA2, 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-PLA2 mass decreased from 618 (493719) to 588 (465698) mu g/L (P <0.001), and apoB-Lp-PLA2 decreased from 0.276 (0.2000.351) to 0.256 (0.1890.328) 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-PLA2 mass were correlated positively with changes in total cholesterol, LDL cholesterol and non-HDL cholesterol (r = 0.2600.276, P <0.05 to P <0.02), whereas changes in apoB-Lp-PLA2 were correlated positively with changes in non-HDL cholesterol and in the total cholesterol/HDL cholesterol ratio (r = 0.2320.385, P <0.050.01). Conclusion Both plasma Lp-PLA2 mass levels and apoB-Lp-PLA2 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 0.20). 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. (Chin. Lab. 2012;58:1231-1239. DOI: 10.7754/Clin.Lab.2012.120323

Plasma lipoprotein-associated phospholipase A(2) mass is elevated in STEMI compared to non-STEMI patients but does not discriminate between myocardial infarction and non-cardiac chest pain

<p>Background: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) mass predicts future cardiovascular events in the non-acute setting. We tested the extent to which Lp-PLA(2) is elevated in patients with acute coronary syndrome.</p><p>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-PLA(2) mass was measured using turbidimetric immunoassay.</p><p>Results: Lp-PLA(2) mass was not different between MI patients and patients with non-cardiac chest pain (231 +/- 72 mu g/l vs.243 +/- 88 mu g/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, 0.69-123), p = 0.58). However, Lp-PLA(2) 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-PLA(2) (r = 0.183, p = 0.034).</p><p>Conclusions: In the acute setting, plasma Lp-PLA(2) mass is not elevated in MI patients, although Lp-PLA(2) mass appears to relate to the severity of myocardial damage. (c) 2013 Elsevier B.V. All rights reserved.</p>

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

<p>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.</p><p>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).</p><p>Results: Plasma PCSK9 was increased at baseline in proteinuric subjects (213 [161-314] vs. 143 [113-190] ug/L in controls, P</p><p>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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.</p>

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 6.5 mmol/L) and 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

Metabolic Effects of High Altitude Trekking in Patients With Type 2 Diabetes

Item does not contain fulltextOBJECTIVE 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 muU/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

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. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Relative bias (%) of GOX based BGMs compared to the Hexokinase laboratory reference method at different simulated altitudes (10 mmol/L glucose sample).

<p>Note: normobaric BGMs stay at sea level. (normo =  bias under normobaric conditions (sea level); hypo =  bias under hypobaric conditions (simulated altitude),</p><p>* =  reference method).</p