Hemoglobin levels and coronary heart disease risk by age, race, and sex in the reasons for geographic and racial differences in stroke study (REGARDS).

Higher and lower hemoglobin concentrations are associated with coronary heart disease (CHD), but whether this risk is consistent across age, sex, and race is unclear. The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study is an observational cohort study of 30 239 black, and white, adults aged 45 and older recruited 2003-7. Participants were included if they had hemoglobin measures, were CHD-free at baseline, and had all baseline variables. The primary outcome was incident CHD. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD by hemoglobin concentration. This was expressed as a continuous variable and divided into age-, sex-, and race-specific quintiles. The 16 332 participants were included, contributing 114 362 person-years of follow-up and 915 incident CHD events. The mean age was 63 years, 35% were male, 41% were black, and the mean baseline hemoglobin was 13.6 g/dL (SD 1.4). A significant non-linear association between hemoglobin and CHD was identified (P < .001). This association differed significantly by race (P = .025) but not by sex or age. In whites, the risk for incident CHD was higher in the lowest (HR 2.28, 95% CI 1.61, 3.33) and highest (HR 1.94, 95% CI 1.35, 2.79) hemoglobin quintiles relative to the third quintile. For blacks, only those in the lowest hemoglobin quintile had an increased risk for incident CHD events (HR 1.70, 95% CI 1.20, 2.41). Hemoglobin is an independent risk factor for CHD in whites and blacks but with different hemoglobin concentrations conferring different risks.

Risk factors for cancer-associated venous thromboembolism: The venous thromboembolism prevention in the ambulatory cancer clinic (VTE-PACC) study.

BACKGROUND: The Khorana Score is a validated risk score for predicting 6-month incidence of cancer-associated venous thromboembolism (CAT) among patients starting chemotherapy. Venous thromboembolism (VTE) risk factors important in the general population, including age, sex, prior VTE, and hospitalization, are not included in this score, their association with VTE in cancer patients is unknown. OBJECTIVE: To examine risk factors for CAT and the impact of incorporating longitudinal hospitalization into risk assessment. METHODS: Risk factors were recorded among patients starting chemotherapy at a single institution from 2012-14. Hospitalization and time-periods after hospitalization were assessed as time-varying covariates. Logistic regression was used to determine factors related to 6-month CAT risk (the Khorana Score endpoint). Proportional hazard models were used for risk factor identification throughout the 3-year observation period. RESULTS: Among 1,583 patients starting chemotherapy (mean age 60, 48% male), 187 developed CAT (11.8%) with 129 (69%) cases occurring within 6 months of starting chemotherapy. In the 6-month analysis, no additional risk factors were associated with CAT. In the 3-year analysis, male sex (HR 1.57, 95%CI 1.21, 2.07), prior VTE (HR 2.12, 95%CI 1.41, 3.18), and hospitalization (HR 2.69, 95%CI 1.92, 3.75) were associated with increased hazard of CAT, adjusting for risk factors in the Khorana score. CONCLUSIONS: When time-to-event data were incorporated into CAT risk assessment, male sex, prior VTE, and hospitalization were important risk factors. These data highlight the need to consider dynamic methods for assessing VTE risk in cancer patients, with particular attention to the period around hospitalizations.

Association of sickle cell trait with atrial fibrillation: The REGARDS cohort.

BACKGROUND: Sickle cell trait (SCT), sickle cell disease's (SCD) carrier status, has been recently associated with worse cardiovascular and renal outcomes. An increased prevalence of atrial fibrillation (AF) is documented in SCD patients; however, studies in individuals with SCT are lacking. OBJECTIVES: To determine the association of SCT with AF. METHODS: Among African-American participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study we assessed the association of SCT (by ECG or medical history) with prevalent AF using logistic regression adjusting for age, sex, income, education, history of stroke, myocardial infarction, diabetes, hypertension, and chronic kidney disease. A second evaluation was performed a mean of 9.2 years later among available participants, and the same model was used to test the association of SCT with incident AF. RESULTS: In 10,409 participants with baseline ECG data and genotyping, 778 (7.5%) had SCT and 811 (7.8%) had prevalent AF. After adjusting for age, sex, education and income, SCT was associated with AF, OR 1.32 (95% CI 1.03-1.70). The association with incident AF assessed at the second in-home visit with the same adjustments was similar; OR 1.25 (95% CI 0.77-2.03). CONCLUSIONS: SCT was associated with a higher prevalence of AF and a non-significantly higher incident AF over a 9.2 year period independent of AF risk factors. SCT remained associated with prevalent AF after adjusting for potential factors on the causal pathway such as hypertension and chronic kidney disease suggesting alternate mechanisms for the increased risk.

Thrombotic Thrombocytopenic Purpura Associated with Pazopanib.

A 76-year-old male with metastatic renal carcinoma on day 24 of pazopanib was admitted with complaints of emesis, confusion, and hematuria. Laboratory testing showed acute kidney injury, hyperbilirubinemia, and thrombocytopenia. Scattered schistocytes were seen on peripheral smear, and he was diagnosed with thrombotic microangiopathy (TMA). He was started on daily, one-volume plasma exchange with rapid improvement in thrombocytopenia. ADAMTS13 activity returned as undetectably low with no inhibitor detected. After cessation of plasmapheresis, repeat ADAMTS13 activity returned as normal. Unfortunately, his platelet count started to downtrend within four days after developing septicemia thought to be due to a catheter-associated infection. He was placed on comfort care measures after discussion with his family. An autopsy listed the major cause of death as metastatic renal cell carcinoma. According to two separate systematic reviews, there have been no cases of proven drug-induced TMA where decreased ADAMTS13 activity was the identified mechanism. While pazopanib is also associated with TMA, this unique case suggests a novel potential mechanism for TMA associated with pazopanib and brings forth "drug-induced thrombotic thrombocytopenic purpura" that quickly responds to plasmapheresis as a possible new diagnostic entity requiring prompt recognition and treatment.