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Abstract: SA-OR048

Genomic Characterization of Monogenic Hypertension in a Multiethnic Cohort

Session Information

Category: Hypertension and CVD

  • 1401 Hypertension and CVD: Epidemiology, Risk Factors, and Prevention

Authors

  • Johnson, Kipp W., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Do, Ron, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Hypertension is a major risk factor for adverse outcomes, but secondary hypertension may not be not appropriately diagnosed. We sought to ascertain prevalence of monogenic hypertension mutations, and their associations with blood pressure and clinical outcomes.

Methods

In 10,782 individuals of predominantly African (n=4,502) or Hispanic/Latino (n=4,621) ancestry, we examined Clinvar mutations pathogenic for secondary hypertension with systolic, diastolic, and mean arterial blood pressures; hypertension-associated composite clinical outcome; acute systolic blood pressure elevation rates, and appropriate diagnosis.

Results

536 individuals (4.9%) possessed pathogenic mutations. Individuals with pathogenic mutations had 11% increased risk for adverse outcomes (95% CI 1.01-1.20) and had elevated mean arterial (2±0.36 mmHg; p<0.01), systolic (3.22±0.55 mmHg, p<0.001), and diastolic (1.19±0.34) blood pressures. Individuals with a pheochromocytoma and paraganglioma-associated mutation had 2.5-fold higher rates (95% CI 1.8-3.4) for acute SBP elevations above 200 mmHg. Only 4.5% of individuals with pathogenic mutation had appropriate diagnoses of secondary hypertension and 5.4% received appropriate biochemical evaluations. The majority were diagnosed with essential hypertension (65.9%). (Figure 1)

Conclusion

Pathogenic mutations were more frequent in Hispanic Americans. Individuals with pathogenic monogenic mutations for secondary hypertension have higher blood pressures, increased rates of acute blood pressure elevation, and elevated risk for adverse clinical outcomes. The majority of individuals with pathogenic mutations were not appropriately evaluated or diagnosed. These results suggest a need for diversity in the study of rare genetic diseases, and that a genotypic approach for diagnosis of hypertension may be beneficial.

Funding

  • NIDDK Support