Lipid-lowering Therapies in Myositis.

PURPOSE OF REVIEW: The use of lipid-lowering therapies in patients with idiopathic inflammatory myopathies (IIM) is complicated and there are no guidelines for diagnosing, monitoring, or treating atherosclerotic cardiovascular disease (ASCVD) in this group of patients. RECENT FINDINGS: The use of lipid-lowering therapies, especially statins, is recommended in patients with increased risk for ASCVD, which includes patients with inflammatory diseases, based on recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for ASCVD management. There is accumulating evidence that patients with IIM are at increased risk for ASCVD, similar to other inflammatory diseases. Lipid-lowering therapies have side effects that may be pronounced or confounding in myositis patients, potentially limiting their use. Statins are specifically contraindicated in patients with anti 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be safe and potentially beneficial in patients with IIM. Here, we propose a framework for (1) ASCVD risk assessment and treatment based on ACC/AHA ASCVD primary prevention guidelines; (2) myositis disease monitoring while undergoing lipid-lowering therapy; and (3) management of statin intolerance, including, indications for the use of PCSK9 inhibitors.

Brain-Type Natriuretic Peptide and Amino-Terminal Pro-Brain-Type Natriuretic Peptide Discharge Thresholds for Acute Decompensated Heart Failure: A Systematic Review.

BACKGROUND: Acute decompensated heart failure (ADHF) requiring hospitalization is associated with high postdischarge mortality and readmission rates. PURPOSE: To examine the association between achieving predischarge natriuretic peptide (NP) thresholds and mortality and readmission rates in adults hospitalized for ADHF. DATA SOURCES: Multiple databases from 1947 to October 2016 (English-language studies only). STUDY SELECTION: Trials and observational studies that compared mortality and readmission outcomes between patients with ADHF achieving a specific predischarge NP goal and those not achieving the goal. DATA EXTRACTION: Two investigators independently extracted study characteristics and assessed study risk of bias. One author graded the overall strength of evidence, with review by a second author. DATA SYNTHESIS: One randomized trial, 3 quasi-experimental studies, and 40 observational studies were identified. The most commonly used thresholds were a brain-type NP (BNP) level of 250 pg/mL or less or an amino-terminal pro-brain-type NP (NT-proBNP) decrease of at least 30%. Achievement of absolute BNP thresholds reduced postdischarge all-cause mortality (7 of 8 studies) and the composite outcome of mortality and readmission (12 of 14 studies). Achievement of percentage-change BNP thresholds reduced the composite outcome (5 of 6 studies), and achievement of percentage-change NT-proBNP thresholds reduced all-cause and cardiovascular mortality (2 of 4 studies) and the composite outcome (9 of 9 studies). All findings were low-strength. The randomized trial, assessed as having high risk of bias, suggested that a predischarge decrease in NT-proBNP level was associated with lower risk for the composite outcome. Two quasi-experimental studies and 5 observational studies had low risk of bias. Low-risk-of-bias studies had outcome estimates similar in magnitude and direction to estimates from high-risk-of-bias studies. LIMITATION: Most studies failed to adjust for critical confounders and had inadequate definition or assessment of exposures and outcomes. CONCLUSION: Low-strength evidence suggests an association between achieving NP predischarge thresholds and reduced ADHF mortality and readmission. PRIMARY FUNDING SOURCE: None.

Autoantibody clustering of lupus-associated pulmonary hypertension.

OBJECTIVE: To define the SLE phenotype associated with pulmonary hypertension using multiple autoantibodies. METHODS: 207 (8%) patients with SLE with pulmonary hypertension, defined as a right ventricular systolic pressure greater than 40 mm Hg on transthoracic echocardiogram or as pulmonary artery dilatation on CT of the chest, were identified from the Hopkins Lupus Cohort (94.2% female; 56.5% African-American, 39% Caucasian; mean age 45.6 years). 53 patients were excluded from the clustering analysis due to incomplete autoantibody profiles. Agglomerative hierarchical clustering algorithm with Ward's method was used to cluster the patients with pulmonary hypertension, based on their autoantibodies. Autoantibodies used in the clustering analysis included lupus anticoagulant, anticardiolipin, anti-beta 2 glycoprotein I, antidouble-stranded DNA, anti-Sm (anti-Smith), antiribonucleoprotein, false positive-rapid plasma reagin, anti-Ro, anti-La and hypocomplementaemia (C3 ever low or C4 ever low). The Dunn index was used to internally validate the clusters. Bootstrap resampling derived the mean Jaccard coefficient for each cluster. All analyses were performed in R V.3.6.1 using the packages cluster, fpc and gplots. RESULTS: A significantly higher prevalence of pulmonary hypertension in African-American patients with SLE, compared with Caucasian patients with SLE (11.5% vs 5.9%, p<0.0001), was found. Based on equivalent Dunn indices, the 154 patients with SLE-associated pulmonary hypertension with complete autoantibody data were divided into five clusters, three of which had mean Jaccard coefficients greater than 0.6. Hypocomplementaemia, renal disorder and age at diagnosis significantly differed across clusters. One cluster was defined by antiphospholipid antibodies. One cluster was defined by anti-Ro and anti-La. One cluster had low frequencies of all antibodies. CONCLUSION: SLE-associated pulmonary hypertension disproportionately affects African-American patients. Pulmonary hypertension in SLE is defined by five autoantibody clusters. Antiphospholipid antibodies, anti-Ro and anti-La positivity, serological activity, and age at pulmonary hypertension diagnosis significantly differed across clusters, possibly indicating different pathophysiological mechanisms.