Characteristics of REPRIEVE Trial Participants Identifying Across the Transgender Spectrum.

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.

The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data.

Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).

Background: Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk.

Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers.

Background: People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown.

Methods: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs.

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

Background And Aims: Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored.

Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease.

In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium.

Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH.

Background: Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina.

Objectives: This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD.

Methods: We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy.

Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects.

Background: Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity.

Methods: We performed a clinical study of 19 healthy volunteers.

Clinical characteristics and outcomes of patients with and without diabetes in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.

Aims: Hypothesis 1 of the Surgical Treatment for Ischemic Heart Failure (STICH) trial enrolled 1212 patients with an LVEF of ≤35% and CAD amenable to coronary artery bypass grafting (CABG). Patients were randomized to CABG and optimal medical therapy (MED) or MED alone. The objective was to assess whether or not patients with diabetes mellitus (DM) enrolled in the STICH trial would have greater benefit from CABG than patients without DM.

Immunologic effects of hydroxyurea in sickle cell anemia.

Background And Objective: Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.

Hydroxyurea and growth in young children with sickle cell disease.

Background: Growth impairment is a known complication of sickle cell disease. Effects of hydroxyurea (HU) on growth in very young children are not known.

Methods: Height, weight, BMI, and head circumference (HC) were compared with World Health Organization (WHO) standards in BABY HUG, a multicenter, randomized, double-blinded, placebo-controlled 2-year clinical trial of HU in 193 children 9 to 18 months of age.

Weight Loss Programs May Have Beneficial or Adverse Effects on Fat Mass and Insulin Sensitivity in Overweight and Obese Black Women.

Objective: Weight loss interventions have produced little change in insulin sensitivity in black women, but mean data may obscure metabolic benefit to some and adverse effects for others. Accordingly, we analyzed insulin sensitivity relative to fat mass change following a weight loss program.

Design And Methods: Fifty-four black women (BMI range 25.

Insulin and extremity muscle mass in overweight and obese women.

Background: Obesity disproportionately affects women, especially those of African descent, and is associated with increases in both fat and muscle masses.

Objective: Although increased extremity muscle mass may be compensatory to fat mass load, we propose that elevated insulin levels resulting from diminished insulin sensitivity may additionally contribute to extremity muscle mass in overweight or obese women.

Methods: The following measurements were performed in 197 non-diabetic women (57% black, 35% white; age 46±11 years (mean±s.

NHLBI clinical trials workshop: an executive summary.

On September 13-14, 2010, the National Heart, Lung and Blood Institute (NHLBI) organized a workshop: 'Clinical Trials: Past, Present and Future'. The workshop covered many areas in clinical trials, including the history of clinical trials at NHLBI, Bayesian clinical trials, surrogate endpoints, reporting clinical trials, handling missing data, flexible designs and adaptive trials, personalized medicine and genomic clinical trials, and comparative effectiveness research. In this report, we summarize the main discussions and conclusions based on the presentations of the invited speakers at the workshop.

Changes in exercise capacity in subjects with cardiac asymptomatic hereditary hemochromatosis during a follow-up after 5 yrs.

Objective: A long-term effect of hereditary hemochromatosis (HH) on aerobic exercise capacity (AEC) has not been well described.

Design: Forty-three HH and 21 volunteer control subjects who were asymptomatic underwent cardiopulmonary exercise testing using the Bruce protocol. AEC was assessed with minute ventilation (V(E)), oxygen uptake (V(O)(2)), and carbon dioxide production (V(CO)(2)) at baseline and at a follow-up assessment after 5 yrs.

Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis.

High-density lipoprotein cholesterol efflux, nitration of apolipoprotein A-I, and endothelial function in obese women.

Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.

Changes in left ventricular diastolic function of asymptomatic hereditary hemochromatosis subjects during five years of follow-up.

We have previously reported that left ventricular (LV) diastolic function in those with cardiac asymptomatic hereditary hemochromatosis (HH) is similar to that of volunteer control (VC) subjects, despite a presence of augmented left atrial contractile function. However, concern still exists that those with HH might gradually develop LV diastolic dysfunction despite receiving conventional phlebotomy treatment. To address this concern, we prospectively monitored the LV diastolic function of those with HH and VCs during a 5-year period.

Stroke With Transfusions Changing to Hydroxyurea (SWiTCH): a phase III randomized clinical trial for treatment of children with sickle cell anemia, stroke, and iron overload.

Background: Stroke occurs in 5-10% of children with sickle cell anemia (SCA) and has a high (>50%) risk of recurrence without therapy. Chronic monthly erythrocyte transfusions effectively prevent recurrent stroke, but their long-term use is limited by serious side effects, including iron overload. An alternative to transfusion for secondary stroke prevention in SCA is needed, especially one that also improves the management of iron overload.

Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).

Background: Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects.

Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity.

In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity.