Assessing Glycosylated Hemoglobin Thresholds for Development of Cardiovascular Disease by Racial and Ethnic Groups.

BACKGROUND: Diabetes is the strongest risk factor for cardiovascular disease, and although glycosylated hemoglobin (HbA1c) levels are known to vary by race, no racial and ethnic-specific diagnostic thresholds exist for diabetes in prediction of cardiovascular disease events. The purpose of this study is to determine whether HbA1c thresholds for predicting major adverse cardiovascular events (MACEs) differ among racial and ethnic groups. METHODS AND RESULTS: This is a retrospective cohort study of Kaiser Permanente Northern California adult members (n=309 636) with no history of cardiovascular disease who had HbA1c values and race and ethnicity data available between 2014 and 2019. Multivariable logistic regression was used to evaluate the odds of MACEs by the following racial and ethnic groups: Filipino, South Asian, East Asian, Black, White, and Hispanic. A Youden index was used to calculate HbA1c thresholds for MACE prediction by each racial and ethnic group, stratified by sex. Among studied racial and ethnic groups, South Asian race was associated with the greatest odds of MACEs (1.641 [95% CI, 1.456-1.843]; P<0.0001). HbA1c was a positive predictor for MACEs, with an odds ratio of 1.024 (95% CI, 1.022-1.025) for each 0.1% increment increase in HbA1c. HbA1c values varied between 6.0% and 7.6% in MACE prediction by race and ethnicity and sex. White individuals, South Asian individuals, East Asian women, and Black men had HbA1c thresholds for MACE prediction in the prediabetic range, between 6.0% and 6.2%. Black women, Hispanic men, and East Asian men had HbA1c thresholds of 6.2% to 6.6%, less than the typical threshold of 7.0% that is used as a treatment goal. CONCLUSIONS: Findings suggest that the use of race and ethnic- and sex-specific HbA1c thresholds may need to be considered in treatment goals and cardiovascular disease risk estimation.

Significance of Coronary Artery Calcium Found on Non-Electrocardiogram-Gated Computed Tomography During Preoperative Evaluation for Liver Transplant.

Guidelines to evaluate patients for coronary artery disease (CAD) during preoperative evaluation for orthotopic liver transplantation (OLT) are conflicting. Cardiac catheterization is not without risk in patients with end-stage liver disease. No study to date has looked at the utility of non-electrocardiogram-gated chest computed tomography (CT) in the preliver transplant population. Our hypothesis was that coronary artery calcium scores (CACSs) from chest CT scans ordered during the liver transplant workup can identify patients who would benefit from invasive angiography. Nine hundred and fifty-three patients who underwent coronary angiography as part of their OLT workup were considered. Charts were randomly selected and reviewed for the presence of a chest CT performed before coronary angiography during the OLT workup. Agatston and Weston scores were calculated. CACS results were compared with coronary angiography findings. Nine of 54 patients were found to have obstructive CAD by angiography. Receiver-operating characteristic analysis demonstrated that an Agatston score of 251 and a Weston score of 6 maximized sensitivity and specificity for detection of obstructive coronary disease. An Agatston score <4 or Weston score <2 excluded the presence of obstructive CAD; using these thresholds, 13 patients (24%) or 15 patients (28%), respectively, could have theoretically avoided catheterization without missing significant CAD. In conclusion, our data identify the strength of CACS in ruling out coronary disease in patients being evaluated for OLT. Calcium scoring from non-electrocardiogram-gated CT studies may be integrated into preoperative algorithms to rule out obstructive CAD and help avoid invasive angiography in this high-risk population.

Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke.

BACKGROUND AND PURPOSE: Individuals with migraine are at higher risk for stroke, but the mechanism has not been established. On the basis of the association between migraine and intracardiac right-to-left shunt, it has been proposed that stroke in migraineurs could be caused by a paradoxical embolus passing through a patent foramen ovale (PFO) or pulmonary arteriovenous malformation. The aim of this study was to determine the prevalence of PFO with right-to-left shunt in patients who presented with cryptogenic stroke and had a history of migraine. METHODS: Patients between 18 and 60 years old who presented with an ischemic stroke were characterized based on ASCOD phenotyping (atherosclerosis; small-vessel disease; cardiac pathology; other causes; dissection). A migraine diagnosis was identified by reviewing physician notes, and frequent aura was defined if present in at least 50% of attacks. A PFO with right-to-left shunt diagnosis was identified by the presence of a positive bubble contrast study with either transcranial Doppler, transthoracic, or transesophageal echocardiography. RESULTS: Of the 712 patients who presented with ischemic stroke, 127 (18%) were diagnosed as cryptogenic; 68 patients had adequate testing for PFO and a documented migraine history. The prevalence of PFO in patients with cryptogenic stroke without migraine was elevated (59%) compared with the general population (18%). Patients with both cryptogenic stroke and migraine had a higher prevalence of PFO (79%). In patients with cryptogenic stroke who had migraine with frequent aura, the prevalence of PFO was 93%. Only 5 patients (4%) had a history compatible with migrainous infarction. CONCLUSIONS: In patients with cryptogenic stroke who have migraine, there is a high prevalence (79%) of PFO with right-to-left shunt. The timing of the stroke in migraineurs is usually not related to a migraine attack. These observations are consistent with the hypothesis that the mechanism of stroke in migraineurs is most likely because of a paradoxical embolus. Future cryptogenic stroke classification schemes should consider including PFO as a separate etiologic category.

BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells.

BACKGROUND: BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which is thought to protect a variety of cancer cells from apoptosis. The main objective of the present study was to investigate whether BIRC6 plays a role in prostate cancer and could be useful as a novel therapeutic target. METHODS: BIRC6 expression in cell lines was assessed using Western blot analysis and in clinical samples using immunohistochemistry of tissue microarrays. The biological significance of BIRC6 was determined by siRNA-induced reduction of BIRC6 expression in LNCaP cells followed by functional assays. RESULTS: Elevated BIRC6 protein expression was found in prostate cancer cell lines and clinical specimens as distinct from their benign counterparts. Increased BIRC6 expression was associated with Gleason 6-8 cancers and castration resistance. Reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation which was associated with an increase in apoptosis and a decrease in autophagosome formation. Doxorubicin-induced apoptosis was found to be coupled to a reduction in BIRC6 protein expression. CONCLUSION: The data suggest a role for BIRC6 in prostate cancer progression and treatment resistance, and indicate for the first time that the BIRC6 gene and its product are potentially valuable targets for treatment of prostate cancers.