Objective-High-density lipoprotein (HDL) is a heterogeneous lipoprotein class and there is no consensus on the value of HDL subspecies in coronary heart disease (CHD) risk assessment. We tested the hypothesis whether specific HDL subpopulations are significantly associated with CHD-prevalence. Methods and Results-ApoA-I concentrations (mg/dL) in HDL subpopulations were quantitatively determined by native 2d gel electrophoresis, immunoblotting, and image analysis in male participants in the Framingham Offspring Study (FOS). CHD cases (nϭ169) had higher pre␤-1 and ␣-3 particle and lower ␣-1, pre␣-3, and pre␣-1 particle levels than either all (nϭ1277) or HDL cholesterol-matched (nϭ358) controls. ␣-1 and pre␣-3 levels had an inverse association, whereas ␣-3 and pre␣-1 particle levels had a positive association with CHD prevalence after adjusting the data for established CHD risk factors. Standardized logit coefficients indicated that ␣-1 HDL was most significantly associated with CHD prevalence. Moreover, each mg/dL increase in ␣-1 particle level decreased odds of CHD by 26% (PϽ0.0001), whereas each mg/dL increase in HDL cholesterol decreased odds of CHD by 2% in a model including all established CHD risk factors. Conclusions-Specific HDL subpopulations were positively correlated, whereas others were inversely correlated with CHD prevalence in male subject in the FOS, indicating that the various HDL particles might have different roles in the cause of CHD. [1][2][3][4] Traditionally, HDL has been separated into major subclasses by polyanion precipitation, ultracentrifugation (HDL2 and HDL3), or by the apolipoprotein content, distinguishing particles containing only apoA-I (LpA-I), the major apolipoprotein of HDL, from particles containing both apoA-I and apoA-II (LpA-I:A-II). None of these techniques has provided any convincing evidence that 1 kind of HDL subfraction has any greater cardioprotective function than another. [5][6][7][8][9][10] The lack of agreement among these studies is probably related to the fact that all of these HDL subfractions are themselves heterogeneous, containing a variety of different HDL subspecies with possibly different physiological functions.Our laboratory uses native 2-dimensional gel electrophoresis, immunoblotting, and image analysis to separate HDL subpopulations quantitatively from plasma with highresolution based on electrophoretic charge and particle size. 11 We determine apoA-I content, not cholesterol, in these particles. This method has been useful in studies of HDL metabolism and cholesterol transport from cells because it separates intermediates in these processes. 12 A small casecontrol study indicated that coronary heart disease (CHD) patients not only had HDL deficiency but also had a major rearrangement in the apoA-I-containing HDL subpopulations with significantly lower levels of the large ␣-1 and pre␣-1 (Ϸ11 nm), and higher levels of the small ␣-3 (Ϸ8.4 nm) and pre␤-1 (Ϸ5.6 nm) HDL particles than controls. 13 Among these particles, ␣-3 contains both apoA-I and apoA-...

Objective-We examined the effects of simvastatin-niacin and antioxidant vitamins on changes in high-density lipoprotein (HDL) subpopulations and alterations in coronary artery stenosis, as assessed by angiography. Methods and Results-Lipids, lipoproteins, and HDL particles were measured on and off treatment in 123 subjects of the HDL-Atherosclerosis Treatment Study. Patients were assigned to 4 treatment groups, simvastatin-niacin, simvastatinniacin-antioxidant vitamins, antioxidant vitamins, and placebo. Subjects were followed for 3 years on treatment and then for 2 months off treatment. Simvastatin-niacin significantly increased the 2 large apoA-I-containing HDL subpopulations, ␣ 1 and pre␣ 1 , and significantly decreased the 2 smallest particles, pre␤ 1 and ␣ 3 , compared with values obtained from the same patients off treatment. Adding antioxidant vitamins to the lipid-modifying agents blunted these effects (not significant). A significant negative correlation (rϭϪ0.235; PϽ0.01) between the changes in ␣ 1 HDL particle concentration and coronary artery stenosis was noted. Subjects in the third tertile (157% increase in ␣ 1 ) had no progression of stenosis in the 3-year follow-up period, whereas subjects in the first tertile (15% decrease in ␣ 1 ) had an average of 2.1% increase in stenosis. Conclusions-Simvastatin-niacin therapy significantly increased the large apoA-I-containing ␣ 1 HDL particles. This increase was significantly associated with less progression of coronary stenosis even after adjusting for traditional risk factors.

Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had ‫ف‬ 50% lower pre ␤ -1 and more than 2-fold higher levels of ␣ -1 and pre ␣ -1 particles than controls. Three of the five heterozygotes' ␣ -1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre ␤ -1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of ␣ -1 containing apoA-I but no apoA-II, represent an improved antiatherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles. -Asztalos, B. F., K. V. Horvath, K. Kajinami, C. Nartsupha, C. E. Cox, M. Batista, E. J. (1, 2). The major role of CETP is a net transfer of CE from HDL to TG-rich lipoprotein (TRL) and of LDL and TG from TRL to LDL and HDL. CETP mRNA is expressed in several tissues, but the majority of circulating CETP originates from the liver (3).CETP plays a key role in HDL metabolism (4). It regulates total plasma HDL-cholesterol (HDL-C) level and also facilitates the remodeling of HDL particles (5). A high CETP concentration correlates with a low HDL-C level, a strong risk factor for coronary artery disease (6). On the other hand, Asian subjects with CETP deficiency have markedly increased HDL-C (3-to 6-fold) and apoA-I concentrations (7-9). CETP deficiency-induced increase in HDL-C level is mainly found in the large HDL2 subclass. Moreover, the average HDL size of CETP-deficient subjects is significantly increased and enriched in cholesterol (10). These large HDL particles have been reported to be less effective in promoting cholesterol efflux from lipidloaded macrophages than HDL particles of control subjects (11).Several mutations of the CETP gene have been identified as causes of CETP deficiency and increased HDL-C levels. These include a G-to-A substitution within intron 14 at the donor splice site (Int14A), a mutation that is present in up to 2% of the total Japanese population and in as many as 27% of people in the Omagari area of Japan, as well as a missense mutation in exon 15 (D422G) present in up to 7% of the Japanese...

Hyperuricemia is a prevalent finding in patients presenting metabolic syndrome, although its clinical meaning is still controversial and often underestimated. Men and women have different serum urate levels at all ages, and the impact of hyperuricemia in cardiovascular and renal outcomes is generally associated with a worse prognosis in women. Recent studies also have called attention to another perspective on hyperuricemia, indicating that it may be not only a consequence of insulin resistance states but also a significant predictor of the development of metabolic syndrome. This review discusses recent evidence related to the clinical significance of hyperuricemia in both sexes and the potential benefits of lowering serum uric acid levels.

Besides a trend toward higher mortality rate observed in the group with liver failure, we found that citrate-based continuous venovenous hemodiafiltration allowed an effective dialysis dose and reasonable filter patency.

No abstract

<b><i>Background:</i></b> Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients. <b><i>Methods:</i></b> We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission. <b><i>Results:</i></b> 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33–4.69], <i>p</i> = 0.005), diuretic use (OR 4.14 [1.27–13.49], <i>p</i> = 0.019), and IMV (OR 7.60 [1.37–42.05], <i>p</i> = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16–4.33], <i>p</i> = 0.023). Overall 60-day mortality was 14.4% {23.8% (<i>n</i> = 24) in the AKI group versus 5% (<i>n</i> = 5) in the non-AKI group (HR 2.79 [1.04–7.49], <i>p</i> = 0.040); and 35.3% (<i>n</i> = 12) in the RRT group versus 10.2% (<i>n</i> = 17) in the non-RRT group, respectively (HR 2.21 [1.01–4.85], <i>p</i> = 0.047)}. <b><i>Conclusions:</i></b> AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients.

Our findings suggest that the combined use of apoptosis and necroptosis inhibitors can provide additional cytoprotection in AKI. Furthermore, this is the first study to demonstrate that Nec-1 inhibits tubular kidney cell death and restores cell viability via a nonapoptotic mechanism.