Clinical and neurohormonal characteristics in African Americans with neurogenic orthostatic hypotension.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is the hallmark of neurodegenerative forms of autonomic failure, including pure autonomic failure, multiple system atrophy, and Parkinson's disease. Studies have shown autonomic physiological differences in Africans Americans (AA) such as lower heart rate variability, enhanced blood pressure reactivity, and blunted sympathetic neural response compared to non-Hispanic whites. However, the clinical characteristics and neurohormonal profile of autonomic failure in AA is unknown. METHODS: A total of 65 patients with nOH participated in this study (9 AA and 56 non-Hispanic whites). Both groups were of similar age and comorbidity status, and they underwent standardized autonomic testing and assessment of neurohormonal levels and renin activity and aldosterone in supine and upright positions. RESULTS: There were no significant differences in baseline autonomic clinical characteristics between non-Hispanic whites and AA with nOH. Non-Hispanic whites demonstrated a significant increase in upright renin activity compared to AA (295 ± 88% vs. 13 ± 13%, respectively). AA showed a blunted increase in aldosterone compared to non-Hispanic whites (188 ± 27% vs. 59 ± 38%, respectively). These results indicated persistent suppression of the renin-angiotensin system in AA, particularly during upright posture. CONCLUSION: Our findings demonstrate that AA with nOH have similar clinical characteristics and hemodynamic autonomic profiles, but lower upright renin activity and aldosterone levels, compared to non-Hispanic whites. Renin suppression persists in AA with severe autonomic failure and can potentially contribute to postural changes and supine hypertension.

Race and sex differences in cardiovascular autonomic regulation.

Racial and ethnic differences in cardiovascular morbidity and mortality persist despite advances in risk factor identification and implementation of evidence-based treatment strategies. African American men and women are disproportionately affected by cardiovascular risk factors, particularly hypertension. In this context, previous studies have identified sex and racial differences in autonomic cardiovascular regulation which may contribute to the development of hypertension and its high morbidity burden among African Americans. In this review, we provide a comprehensive evaluation of the potential pathophysiological mechanisms of blood pressure control and their differences based on sex and race. These mechanisms include obesity-induced sympathetic activation, sympatho-vascular transduction, baroreflex sensitivity and adrenoreceptor vascular sensitivity, which have been the subjects of prior investigation in this field. Understanding the racial differences in the pathophysiology of hypertension and its co-morbid conditions would allow us to implement better treatment strategies tailored to African Americans, with the ultimate goal of reducing cardiovascular mortality in this population.

Suboptimal Performance of Microscopic Colitis Diagnosis Codes: A Bottleneck for Epidemiologic Insights.

INTRODUCTION: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated. METHODS: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts. RESULTS: The PPV was 0.790 and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively. CONCLUSION: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

Investigating the WNT and TGF-beta pathways alterations and tumor mutant burden in young-onset colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the United States. Recent epidemiological evidence demonstrates an increasing incidence of young-onset CRC cases, defined as CRC cases in individuals 50 years old or younger. Studies have established that alterations in both the WNT and TGF-Beta signaling pathways have contributed to CRC development. While this is well understood, the comprehensive analysis of WNT and TGF-Beta pathway alterations in young-onset CRC cases has yet to be investigated. Here, we conducted a comprehensive bioinformatics analysis of mutations associated with each of the WNT and TGF-Beta signaling pathways according to age (≤ 50 years old versus > 50 years old) utilizing published genomic data from the cBioPortal. Chi-square results demonstrated no significant difference in WNT alterations between young-onset CRC and those > 50 years old. However, across all age groups, WNT alterations were frequently found in rectal cancers. We also found that WNT alterations were associated with better outcomes. The mutations associated with TGF-beta were observed at a higher rate in older CRC patients when compared to those ≤ 50 years old. Additionally, these mutations were found more frequently in colon primaries.