APOL1 Testing Can Spur Improved Blood Pressure Control in African Americans with Hypertension


A randomized trial comparing the effects of immediate testing and disclosure versus delayed testing, results suggest disclosing results of APOL1 testing led to reductions in blood pressure and meaningful lifestyle changes among patients with hypertension.

Girish Nadkarni, MD

Girish Nadkarni, MD

Disclosure of genetic testing results for risk variants in the apolipoprotein L1 (APOL1) gene for patients with African ancestry contributed to reductions in blood pressure, increased screening for kidney disease, and positive behavior changes, according to results of a recent randomized trial.

A pragmatic randomized clinical trial of 2050 adults of African ancestry with hypertension and without existing chronic kidney disease (CKD), results of the study provide evidence detailing the benefits of testing and disclosing APOL1 genetic results and how these benefits differ among patients with high-risk APOL1 genotypes compared to low-risk APOL1 genotypes.

"While race is a social construct, and this disparity is multifactorial and structural, ancestry has genetic components,” said lead investigator Girish N. Nadkarni, MD, MPH, the Irene and Dr. Arthur M. Fishberg Professor of Medicine at Icahn Mount Sinai, in a statement. “For many years, researchers have wondered whether reporting APOL1 genetic test results would help improve clinical management. This is the first pragmatic randomized clinical trial to test this out.”

With risk variants in the APOL1 gene common among those of African ancestry and associated with increased risk of kidney failure and hypertension among these patients, some hypothesize genetic testing and disclosure of results could significantly improve hypertension management. With this in mind, the GUARDD trial was designed as a randomized clinical trial and conducted across 15 medical centers in 2 health systems in New York City.

For inclusion in the trial, patients needed to be of self-identified African ancestry, be 18-70 years of age, have hypertension, and be receiving primary care at a participating site in the past year. For the purpose of analysis, hypertension diagnosis was defined as an EHR diagnosis, taking antihypertensive medications, or having 2 systolic blood pressure readings greater than 140 mmHg at least 6 months apart. Exclusion analysis for the trial included having diabetes, CKD, pregnancy, or cognitive impairment.

As part of study protocol, patients were randomized in a 7:1 ratio to receive immediate or delayed APOL1 genetic testing results from trained staff. Those randomized to delayed testing results received their results at the conclusion of the 12-month follow-up visit. Patients with high-risk genotypes were informed of results in person and those with low-risk genotypes were informed over the phone. All patients received a scripted message conveying talking points surrounding the importance of blood pressure control, asked if they wish to consult with the study’s genetic counselor, and received a low literacy educational booklet with their results.

Investigators compared the change in 3-month systolic blood pressure and 12-month urine albumin screening for kidney disease among high-risk genotypes versus those with low-risk genotypes as the primary outcomes for the trial. Secondary outcomes of interest included differences in systolic blood pressure and urine testing among those in the intervention group versus the control group as well as changes in lifestyle habits, which was a subjective measurement that included dietary and exercise habits.

A total of 2050 patients underwent randomization in the study, with 1795 randomized to testing and 255 in the control group. The overall study cohort had a mean age of 53 (SD, 10) years and 66% were women. Of the 1795 patients in the intervention group, 1561 had a low-risk APOL1 genotype and 234 had a high-risk genotype. At baseline, the mean systolic blood pressure was significantly greater among those with high-risk APOL1 genotypes compared to those with low-risk APOL1 genotypes and controls (137 [SD, 21] vs 134 [SD, 19] vs 133 [SD, 19] mmHg; P=.003 for high-risk vs low-risk APOL1 genotypes; P = .001 for high-risk APOL1 genotypes vs controls).

At 3 months, a greater change in mean systolic blood pressure was observed among those with high-risk genotypes compared to those with low-risk genotypes (6 [SD, 18] vs 3 [SD, 18]; P=.004) and controls (6 [SD, 18] vs 3 [SD, 19] mmHg; P=.01). At 12 months, a 12% increase in urine albumin testing was observed among those with high-risk genotypes compared to a 6% increase in those with low-risk genotypes (P=.10) and a 7% increase among controls (P=.01). Additionally, further analysis indicated patients with high-risk genotypes reported more changes in lifestyle (59% vs 37%; P <.001) and increased blood pressure medication (10% vs 5%; P=.005) use compared to those with low-risk genotypes.

This study, “Effects of Testing and Disclosing Ancestry-Specific Genetic Risk for Kidney Failure on Patients and Health Care Professionals,” was published in JAMA Network Open.

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