SARS-CoV-2-Associated Nephropathy: Direct Renal Infection and Damage

Acute kidney injury is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), principally because of hypotension and decreased kidney perfusion secondary to haemodynamic or haemostatic factors, drug-induced nephrotoxicity, and cytokine storm syndrome related to sepsis. Additionally, several factors support the existence of SARS-CoV-2-associated nephropathy, such as early, new-onset proteinuria and haematuria in many patients, the identification of SARS-CoV-2 viral load in precisely defined kidney compartments, ultrastructural and immunohistochemical evidence of direct viral infection of the kidneys, and, most importantly, morphological alterations associated with cytopathic action induced by the virus. In addition, collapsing glomerulopathy that has been reported in patients of African American descent with underlying apolipoprotein L1 (APOL1) kidney risk alleles and SARS-CoV-2 infection is evidence of a distinct form of SARS-CoV-2-associated nephropathy, the APOL1-SARS-CoV2-associated nephropathy.

The association of alcohol with circulating total fibrinogen and plasma clot density is mediated by fibrinogen and FXIII genotypes

Background Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F) XIII single nucleotide polymorphisms (SNPs). Methods Total fibrinogen, γ’ fibrinogen and clot properties of 2010 healthy Africans residing in South Africa were measured in relation to alcohol intake as well as its markers – gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence. Results Alcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage γ’ fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between γ’ fibrinogen and both %CDT and GGT–CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p < 0.004). Conclusion/s We show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and the gene variants observed here.

The association of alcohol with circulating total fibrinogen and plasma clot density is mediated by fibrinogen and FXIII genotypes

Background: Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and g’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F)XIII single nucleotide polymorphisms (SNPs).Methods: Total fibrinogen, g’ fibrinogen and clot properties of 2010 healthy Africans residing in South Africa were measured in relation to alcohol intake as well as its markers – gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence.Results: Alcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage g’ fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between g’ fibrinogen and both %CDT and GGT–CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p <0.004).Conclusion/s: We show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and gene variants observed here.

The association of alcohol with circulating total fibrinogen and plasma clot density is mediated by fibrinogen and FXIII genotypes

Background Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F)XIII single nucleotide polymorphisms (SNPs). Methods Total fibrinogen, γ’ fibrinogen and clot properties of 2010 healthy black South Africans were measured in relation to alcohol intake as well as its markers – gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence. Results Alcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage γ’ fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between γ’ fibrinogen and both %CDT and GGT–CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p <0.004). Conclusion/s We show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and gene variants observed here.

P6141Associations between atmospheric parameters and haemostatic factors: a case control study

Background One of the biggest health challenges in the 21st century is global climate change. The health effect of climate change is partly mediated through atmospheric parameters. There is a growing concern that atmospheric parameters might increase cardiovascular (CV) morbidity. Increased levels of haemostatic factors are predictors of CV events. The associations between CV diseases and atmospheric parameters have been widely reported, however there are few studies of atmospheric parameters' effects on markers of haemostasis. Purpose We examined the possible association between atmospheric parameters and several haemostatic markers. Methods The study consisted of 3800 hospitalized patients with acute CV diseases (ACVDs) and 260 healthy blood donors. We examined the relationship of haemoglobin (Hgb), white blood cells (WBC), thrombocytes (THR) and local atmospheric parameter conditions (temperature, atmospheric pressure, humidity, wind speed, atmospheric front) on a day-to-day basis in a 5-year period (2009–2013) using a General Additive Model with cubic splines of covariates, regularized by a ridge penalty, and employing generalized cross validation. Atmospheric parameters were allowed to have a lagged effect by up to 21 days. Results Among blood donors, the average of daily temperature lagged by 8–14 days had a significant effect on Hgb, exhibiting a U-shaped relationship, where higher Hgb values were associated with extremities of the observed temperature interval. For ACVD patients, all examined blood test variables has a significant association with at least some of the atmospheric parameters. Hgb was shown to have a negative linear relationship with mean daily humidity, and the average of daily temperature lagged by 15–21 days, while the average of daily temperature variation lagged by 2–7 days had highly non-linear effect. The relative strength of the association with Hgb was largest for daily temperature variation. WBC values had a slightly non-linear positive relationship with atmospheric pressure lagged by 1 day, with WBC being significantly increased above 1030 hPa. THR values decreased linearly with an increase in mean daily temperature averaged for days lagged 15–21. Atmospheric pressure lagged by 1 day also had a significant effect on THR, with a positive linear effect under 1010 and over 1020 hPa but no effect between. The relative effect of atmospheric pressure on THR was twice as large compared to temperature. Conclusions Our study showed that exposure to certain atmospheric parameters is associated with significant changes in haemostatic marker levels. In the context of global climate change, the importance of focusing on atmospheric parameters as minor CV risk factor is substantially growing. A better understanding of the fluctuation of the examined markers, in light of atmospheric parameters, appears to be of particular importance for future studies and could help establish new CV prevention strategies.

Low Self-rated Health Is Related to Blood Hypercoagulability in Patients Admitted with Acute Myocardial Infarction

Self-rated health (SRH) is independently associated with all-cause mortality and adverse cardiovascular outcomes in individuals with and without cardiovascular disease. We examined whether SRH relates to haemostatic factors of a hypercoagulable state with prognostic impact in patients admitted with acute myocardial infarction (MI). We assessed 190 patients (median age: 59 years; all Caucasian; 83% men) within 48 hours of an acute coronary intervention in terms of demographic factors, medical and psychiatric comorbidity, health behaviours, cardiac-related variables and psychosocial characteristics. Patients rated their health state before MI retrospectively with the EuroQol Visual Analogue Scale ranging from 0 (‘worst imaginable health state’) to 100 (‘best imaginable health state’). Circulating levels of fibrinogen, fibrin D-dimer and von Willebrand factor (VWF) antigen were measured the morning after hospital referral. The median score of SRH was 75 (range: 20–100). SRH was inversely associated with fibrinogen (r = − 0.25, p = 0.001) and D-dimer (r = − 0.17, p = 0.021) levels in the bivariate analysis. Stronger relationships emerged for fibrinogen (r = − 0.33, p < 0.001), D-dimer (r = − 0.25, p = 0.001) and also VWF (r = − 0.19, p = 0.015) levels in fully adjusted linear regression models. As for SRH, the Global Registry of Acute Coronary Events (GRACE) risk score was the only covariate showing an independent association with all haemostatic factors (fibrinogen: r = 0.31, D-dimer: r = 0.29, VWF: r = 0.30; all p-values < 0.001). Lower SRH was associated with greater coagulability in patients with acute MI, independent of covariates and comparable with the GRACE risk score. The findings provide a novel psychobiological mechanism that may potentially link SRH with cardiovascular outcome in patients with an acute coronary syndrome.