Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen. Both of these treatments reduce total cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases of HoFH.

Relation between proprotein convertase subtilisin/kexin type 9 and directly measured low-density lipoprotein cholesterol.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of low-density lipoprotein cholesterol (LDL-C) receptor (LDL-R) recycling and, thus, is a determinant of plasma LDL-C concentration. We sought to determine the relation between serum concentrations of PCSK9 and LDL-C while considering a variety of influential variables, including treatment for dyslipidemia. Using a prospective lipid clinic registry, we evaluated clinical variables, the results of advanced lipid testing, and PCSK9 concentrations determined by immunoassay. We evaluated the relationship between directly measured LDL-C and PCSK9 in serum by performing a simple linear regression. Correlation analyses were performed to examine the relationships of PCSK9 to other clinical and laboratory values and to test for differences in median PCSK9 across patient groups. Factors identified as potential predictors were considered jointly in a multivariate model. For the 26 patients in the analyses, a relationship was not detected between LDL-C and PCSK9 (r = 0.009, P = 0.97); however, PCSK9 was correlated with C-peptide (r = 0.48; P = 0.01) and heart rate (r = 0.52; P = 0.006). Median PCSK9 values differed between statin users (284.0 ng/mL [quartile 1 = 241.0, quartile 3 = 468.0]) and nonusers (219.0 ng/mL [quartile 1 = 151.0, quartile 3 = 228.0]; P = 0.02). More investigation is needed to evaluate the relationship between LDL and PCSK9, as well as the determinants of PCSK9, a major factor regulating cholesterol concentrations.

Urinary metabolites in patients undergoing coronary catheterization via the radial versus femoral artery approach.

The transradial approach (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower rates of vascular complications and acute kidney injury when compared to the transfemoral approach (TFA). Urine metabolites and proteins may be useful in identifying the dynamic changes at the vascular endothelial cell level. We attempted to explore the changes in the measurable signals of endothelial and nephron injury within 60 to 90 minutes after catheterization among those with the TRA and TFA approaches. Consecutive patients of a single interventionist who underwent coronary angiography between June 2015 and May 2016 were included. Of the 60 patients included in the analysis, the baseline characteristics were similar between those with a TRA (n = 30) and TFA (n = 30) approach. The values of the biomarkers were natural log transformed for the analysis. We found that the mean values of heat shock protein 27, taurine, and sulfuric acid did not significantly change after the procedure. However, the median value of thioredoxin decreased (P = 0.002) and that of talose increased (P = 0.01) after the procedure. None of the patients in our cohort experienced vascular complications or acute kidney injury. No differences in the values of urinary metabolites (pre, post, and delta) were found between TRA and TFA except for postprocedural thioredoxin. In conclusion, this exploratory study showed no difference in the patterns of acute vascular/renal injury metabolic markers before and after catheterization irrespective of the arterial access site.

Personalized treatment of heart failure with biomarker guidance using a novel disease severity score.

We propose a novel Myocardial Injury Summary Score (MISS) integrating the 4 biomarkers suggested by the 2013 American College of Cardiology/American Heart Association guidelines for management of heart failure. In this case series, we examined 4 heart failure patients who received treatment guided by the biomarker results and 4 patients who received routine clinical management with no information about the biomarkers. Most of the patients receiving biomarker-guided management had medications adjusted based on the biomarker values, while no changes were recommended for patients in the biomarker-blinded category. This case series suggests that biomarker-guided therapy with serial biomarker values leads to timely therapeutic adjustment and that biomarker values as a composite score can be used effectively to measure the severity of heart failure.

Comparative Efficacy of Transradial Versus Transfemoral Approach for Coronary Angiography and Percutaneous Coronary Intervention.

Transradial artery (TRA) approach is associated with fewer vascular complications and reduced mortality in patients at high risk compared with transfemoral approach (TFA). The objective of our study was to compare the characteristics and outcomes of patients who had coronary angiography by TRA and TFA over the course of hospital implementation of this approach. We included 12,928 patients from Baylor University Medical Center and Baylor Heart and Vascular Hospital, Dallas, Texas, who underwent a coronary angiography from January 2008 to March 2015. To control for selection bias and the learning curve, a nested matched study design was used for patients with percutaneous coronary intervention (PCI) with TRA patients matched with TFA by age (±2 years) and calendar year of the procedure in a ratio of 1:3. TRA for PCI increased from nearly 0% in 2008 to 9% in 2014. Including patients from 2011 to 2015 for the analysis, patients with TFA were older (65 ± 12 vs 64 ± 11) and had lower mean body mass index (30 ± 7 vs 33 ± 9 kg/m(2)) than patients with TRA. Patients with TRA had less bleeding, dialysis, pseudoaneurysm, and access site hematomas than the patients with TRA (0.7% vs 0%; p = 0.02). By a conditional logistic regression, we observed fewer complications, readmissions, and in-hospital deaths among TRA patients than the matched TFA patients. In conclusion, patients undergoing angiography with/without PCI through TRA had fewer complications, readmissions, and a shorter length of hospital stay after procedure versus TFA at our hospital.