Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease

Hydrogen sulfide (H2S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adap- tation, and mitochondrial respiration. However, bioavailable levels of H2S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H2S. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfur levels were significantly reduced in Caucasian males with CVD compared with those without the disease. Surprisingly, gender differences of H2S bioavailability were not observed in African Americans, although H2S bioavailability was significantly lower overall in this ethnic group compared to Caucasians. We also performed SNP analysis of H2S synthesizing enzymes and found a significant increase in cystathionine gamma-lyase (CTH) 1364 G-T allele frequency in patients with CVD compared to controls. Lastly, plasma H2S bioavailability was found to be predictive for cardiovascular disease in Caucasian subjects as de- termined by receiver operator characteristic analysis. These findings reveal that plasma H2S bioavailability could be considered a biomarker for CVD in an ethnic and gender manner. Cystathionine gamma-lyase 1346 G-T SNP might also contribute to the risk of cardiovascular disease development

Lipid monitoring after initiation of lipid-lowering therapies: Return of performance measures?

Purpose of review: The 2015 American College of Cardiology (ACC)/American Heart Association (AHA) Focused Update of Secondary Prevention Lipid Performance Measures removed low-density lipoprotein cholesterol (LDL-C) assessment as a performance measure. This review discusses the evidence supporting the importance of lipid monitoring in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD).Recent findings: The 2018 AHA/ACC Multisociety cholesterol guideline (as did the 2013 guideline) recommends a lipid panel after initiating lipid-lowering therapy to monitor adherence and medication efficacy. The 2018 guideline also recommends adding nonstatin therapy in very-high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated statin therapy. The removal of LDL-C monitoring as a performance measure is not consistent with the 2018 cholesterol guidelines. Given the importance of monitoring lipid-lowering medication efficacy and adherence and optimally reducing LDL-C in very-high-risk patients with additional evidence-based nonstatin therapy, LDL-C assessment after initiating lipid-lowering therapy should be reinstated as a performance measure for patients with ASCVD

Temporal trends in lipoprotein(a) concentrations: The atherosclerosis risk in communities study

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person\u27s life is sufficient for cardiovascular risk assessment in all adults. Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline (visit 4) Lp(a) concentrations as normal (\u3c30 mg/dL), borderline-high (30-49 mg/dL), or high (≥50 mg/dL). We compared adults with Lp(a) change ≥20 mg/dL between visits and those with Lp(a) change \u3c20 mg/dL. Multivariable logistic regression analysis was used to identify covariates associated with change in Lp(a) over time. At visit 5, 58.1% of participants with borderline-high Lp(a) concentrations of 30 to 49 mg/dL at visit 4 had high Lp(a) concentrations ≥50 mg/dL. Participants with low Lp(a) (\u3c30 mg/dL) or high Lp(a) (≥50 mg/dL) at visit 4 tended to stay in these respective categories. Black race, female sex, diabetes, hypertension, total cholesterol, and albuminuria were associated with significantly greater probability for Lp(a) change ≥20 mg/dL over time. Conclusions: Our results suggest that adults with borderline-high Lp(a) concentrations may be considered for repeat monitoring of Lp(a) over time, particularly if they are Black, women, or have diabetes, hypertension, and/or elevated albuminuria

Genetic testing for hypertriglyceridemia in academic lipid clinics: Implications for precision medicine-brief report

Background: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown.Methods: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight\u27s Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL).Results: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [P=0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. Conclusions: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies

Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease

Hydrogen sulfide (H2S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of H2S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H2S. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfur levels were significantly reduced in Caucasian males with CVD compared with those without the disease. Surprisingly, gender differences of H2S bioavailability were not observed in African Americans, although H2S bioavailability was significantly lower overall in this ethnic group compared to Caucasians. We also performed SNP analysis of H2S synthesizing enzymes and found a significant increase in cystathionine gamma-lyase (CTH) 1364 G-T allele frequency in patients with CVD compared to controls. Lastly, plasma H2S bioavailability was found to be predictive for cardiovascular disease in Caucasian subjects as determined by receiver operator characteristic analysis. These findings reveal that plasma H2S bioavailability could be considered a biomarker for CVD in an ethnic and gender manner. Cystathionine gamma-lyase 1346 G-T SNP might also contribute to the risk of cardiovascular disease development