Sodium status and kidney involvement during COVID-19 infection

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.</p

Serum paraoxonase-1 activity and risk of incident cardiovascular disease:The PREVEND study and meta-analysis of prospective population studies

Background: Paraoxonase-1 (PON-1) has been suggested to be associated with cardiovascular disease (CVD) risk, however, aspects of the association, such as shape and independence from conventional risk factors are still uncertain. We aimed to assess the association of PON-1 with CVD risk and determine its potential utility for CVD risk prediction. Methods: PON-1 was measured as its arylesterase activity at baseline in the PREVEND prospective study of 6902 participants. Results: During a mean follow-up of 9.3 years, 730 CVD events were recorded. Serum PON-1 was weakly correlated with several cardiovascular risk markers including high-density lipoprotein cholesterol (HDLC) (r = 0.18; P <0.001) and was approximately log-linearly associated with CVD risk. In analyses adjusted for conventional risk factors, the hazard ratio (95% CI) for CVD per 1 standard deviation (SD) increase in loge PON-1 was 0.92 (0.85-0.99; P = 0.020), which remained persistent after additional adjustment for potential confounders 0.93 (0.86-0.99; P = 0.037). The association was attenuated on further adjustment for HDL-C 0.95 (0.88-1.02; P = 0.153). In a meta-analysis of 6 population-based prospective studies involving 15 064 participants and 2958 incident CVD outcomes, the pooled multivariable adjusted (including HDL-C) relative risk (95% CI) for CVD was 0.95 (0.90-1.02; P = 0.138) per 1 SD increase in PON-1 values. Adding PON-1 to a CVD risk prediction model containing conventional risk factors did not improve the C-index or net reclassification. Conclusions: There is an approximately log-linear inverse association between PON-1 activity and CVD risk, which is partly dependent on HDL-C levels. In addition, serum PON-1 activity provides no significant improvement in CVD risk assessment beyond conventional CVD risk factors. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Adiposity Blunts the Positive Relationship of Thyrotropin with Proprotein Convertase Subtilisin-Kexin Type 9 Levels in Euthyroid Subjects

BACKGROUND: Effects of thyroid function status on lipoprotein metabolism may extend into the euthyroid range. Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C). Here, we tested whether plasma PCSK9 correlates with thyroid function in nonobese and obese euthyroid subjects. METHODS: We assessed the extent to which plasma PCSK9 is determined by thyrotropin (TSH) in 74 euthyroid subjects (31 women; TSH between 0.5 and 4.0 mU/L and free thyroxine [FT4] between 11.0 and 19.5 pM) with varying degrees of obesity (body mass index [BMI] ranging from 20.2 to 40.4 kg/m(2)). RESULTS: TSH, FT4, PCSK9, non–high-density lipoprotein cholesterol (non-HDL-C), LDL-C, and apolipoprotein B (apoB) levels were not different between 64 nonobese subjects (BMI<30 kg/m(2)) and 10 obese subjects (BMI≥30 kg/m(2); p>0.20 for each). PCSK9 correlated positively with TSH in nonobese subjects (r=0.285, p=0.023). In contrast, PCSK9 was not associated positively with TSH in obese subjects (r=−0.249, p=0.49). The relationship of PCSK9 with TSH was different between nonobese and obese subjects when taking age, sex, FT4, and the presence of anti-thyroid antibodies into account (multiple linear regression analysis: β=−0.320, p=0.012 for the interaction term between the presence of obesity and TSH on PCSK9), and was also modified by BMI as a continuous trait (β=−0.241, p=0.062 for the interaction term between BMI and TSH on PCSK9). Non-HDL-C, LDL-C, and apoB levels were dependent on PCSK9 in nonobese subjects (p≤0.01 for each), but not in obese subjects (p>0.50), Accordingly, BMI interacted negatively with PCSK9 on non-HDL-C (p=0.028) and apoB (p=0.071). CONCLUSIONS: This study suggests that circulating PCSK9 levels correlate with thyroid function even in the normal range. This relationship appears to be blunted by obesity. Thyroid functional status may influence cholesterol metabolism through the PCSK9 pathway

Advanced glycation end products:An emerging biomarker for adverse outcome in patients with peripheral artery disease

AbstractPatients with peripheral artery disease (PAD) suffer from widespread atherosclerosis. Partly due to the growing awareness of cardiovascular disease, the incidence of PAD has increased considerably during the past decade. It is anticipated that algorithms to identify high risk patients for cardiovascular events require being updated, making use of novel biomarkers. Advanced glycation end products (AGEs) are moieties formed non-enzymatically on long-lived proteins under influence of glycemic and oxidative stress reactions. We elaborate about the formation and effects of AGEs, and the methods to measure AGEs. Several studies have been performed with AGEs in PAD. In this review, we evaluate the emerging evidence of AGEs as a clinical biomarker for patients with PAD

Alcohol Consumption, High-Density Lipoprotein Particles and Subspecies, and Risk of Cardiovascular Disease:Findings from the PREVEND Prospective Study

The associations of HDL particle (HDL-P) and subspecies concentrations with alcohol consumption are unclear. We aimed to evaluate the interplay between alcohol consumption, HDL parameters and cardiovascular disease (CVD) risk. In the PREVEND study of 5151 participants (mean age, 53 years; 47.5% males), self-reported alcohol consumption and HDL-P and subspecies (small, medium, and large) by nuclear magnetic resonance spectroscopy were assessed. Hazard ratios (HRs) with 95% CIs for first CVD events were estimated. In multivariable linear regression analyses, increasing alcohol consumption increased HDL-C, HDL-P, large and medium HDL, HDL size, and HDL subspecies (H3P, H4P, H6 and H7) in a dose-dependent manner. During a median follow-up of 8.3 years, 323 first CVD events were recorded. Compared with abstainers, the multivariable adjusted HRs (95% CIs) of CVD for occasional to light, moderate, and heavy alcohol consumers were 0.72 (0.55-0.94), 0.74 (0.54-1.02), and 0.65 (0.38-1.09), respectively. These associations remained consistent on additional adjustment for each HDL parameter. For CVD, only HDL-C was associated with a statistically significant decreased risk of CVD in a fully adjusted analysis (HR 0.84, 95% CI 0.72-0.97 per 1 SD increment). For coronary heart disease, HDL-C, HDL-P, medium HDL, HDL size, and H4P showed inverse associations, whereas HDL-C and HDL size modestly increased stroke risk. Except for H6P, alcohol consumption did not modify the associations between HDL parameters and CVD risk. The addition of HDL-C, HDL size, or H4P to a CVD risk prediction model containing established risk factors improved risk discrimination. Increasing alcohol consumption is associated with increased HDL-C, HDL-P, large and medium HDL, HDL size, and some HDL subspecies. Associations of alcohol consumption with CVD are largely independent of HDL parameters. The associations of HDL parameters with incident CVD are generally not attenuated or modified by alcohol consumption.</p

Plasma ApoE elevations are associated with NAFLD:The PREVEND Study

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) >= 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI >= 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: beta = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE epsilon 3 epsilon 3 homozygotes, ApoE epsilon 2 carriers, and ApoE epsilon 3 epsilon 4 and epsilon 4 epsilon 4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE geno-types. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD

The predictive value of the antioxidative function of HDL for cardiovascular disease and graft failure in renal transplant recipients

AbstractBackgroundProtection of low-density lipoproteins (LDL) against oxidative modification is a key anti-atherosclerotic property of high-density lipoproteins (HDL). This study evaluated the predictive value of the HDL antioxidative function for cardiovascular mortality, all-cause mortality and chronic graft failure in renal transplant recipients (RTR).MethodsThe capacity of HDL to inhibit native LDL oxidation was determined in vitro in a prospective cohort of renal transplant recipients (RTR, n = 495, median follow-up 7.0 years).ResultsThe HDL antioxidative functionality was significantly higher in patients experiencing graft failure (57.4 ± 9.7%) than in those without (54.2 ± 11.3%; P = 0.039), while there were no differences for cardiovascular and all-cause mortality. Specifically glomerular filtration rate (P = 0.001) and C-reactive protein levels (P = 0.006) associated independently with antioxidative functionality in multivariate linear regression analyses. Cox regression analysis demonstrated a significant relationship between antioxidative functionality of HDL and graft failure in age-adjusted analyses, but significance was lost following adjustment for baseline kidney function and inflammatory load. No significant association was found between HDL antioxidative functionality and cardiovascular and all-cause mortality.ConclusionThis study demonstrates that the antioxidative function of HDL (i) does not predict cardiovascular or all-cause mortality in RTR, but (ii) conceivably contributes to the development of graft failure, however, not independent of baseline kidney function and inflammatory load

Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes:the PREVEND study

Abstract Background Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population. Methods We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function. Results In subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D. Conclusions Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR

Higher Sodium Intake Assessed by 24 Hour Urinary Sodium Excretion Is Associated with Non-Alcoholic Fatty Liver Disease:The PREVEND Cohort Study

A higher sodium intake is conceivably associated with insulin resistant conditions like obesity, but associations of non-alcoholic fatty liver disease (NAFLD) with a higher sodium intake determined by 24 hours (24 h) urine collections are still unclear. Dietary sodium intake was measured by sodium excretion in two complete consecutive 24 h urine collections in 6132 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Fatty Liver Index (FLI) >= 60 and Hepatic Steatosis Index (HSI) >36 were used as proxies of suspected NAFLD. 1936 (31.6%) participants had an FLI >= 60, coinciding with the increased prevalence of type 2 diabetes (T2D), metabolic syndrome, hypertension and history of cardiovascular disease. Sodium intake was higher in participants with an FLI >= 60 (163.63 +/- 61.81 mmol/24 h vs. 136.76 +/- 50.90 mmol/24 h, p = 60 was positively associated with a higher sodium intake when taking account for T2D, a positive cardiovascular history, hypertension, alcohol intake, smoking and medication use (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.44-1.64, p 36 showed similar results. Associations remained essentially unaltered after adjustment for body surface area or waist/hip ratio. In conclusion, suspected NAFLD is a feature of higher sodium intake. Insulin resistance-related processes may contribute to the association of NAFLD with sodium intake