Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program

Elvis A Akwo^{1

2

3}, Cassianne Robinson-Cohen^{1

2

3}, Cecilia P Chung^{4

3

5}, Shailja C Shah^{6

3}, Nancy J Brown^{7

8}, T Alp Ikizler^{1

2

3}, Otis D Wilson^{1

3}, Bryce X Rowan⁹, Megan M Shuey¹⁰, Edward D Siew^{1

2

3}, James M Luther⁷, Ayush Giri^{11

5}, Jacklyn N Hellwege¹⁰, Digna R Velez Edwards^{11

12

13}, Christianne L Roumie¹⁴, Ran Tao^{9

5}, Phil S Tsao^{15

16

17}, J Michael Gaziano^{18

19}, Peter W F Wilson^{20

21}, Christopher J O'Donnell^{19

22}, Todd L Edwards^{13

23}, Csaba P Kovesdy^{24

25}, Adriana M Hung^{1

26

2

3}; VA Million Veteran Program

Affiliations

¹ Division of Nephrology and Hypertension, Department of Medicine (E.A.A., C.R.-C., T.A.I., O.D.W., E.D.S., A.M.H.).
² Vanderbilt Center for Kidney Disease (E.A.A., C.R.-C., T.A.I., E.D.S., A.M.H.).
³ Tennessee Valley Healthcare System, Nashville, VA (E.A.A., C.R.-C., C.P.C., S.C.S., T.A.I., O.D.W., E.D.S., A.M.H.).
⁴ Division of Rheumatology, Department of Medicine (C.P.C.), Vanderbilt University Medical Center, Nashville, TN.
⁵ Vanderbilt Genetics Institute (C.P.C., A.G., R.T.).
⁶ Division of Gastroenterology, Hepatology and Nutrition (S.C.S.), Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Medicine (N.J.B., J.M.L.), Vanderbilt University Medical Center, Nashville, TN.
⁸ Yale School of Medicine, New Haven, CT (N.J.B.).
⁹ Department of Biostatistics, Vanderbilt School of Medicine (B.X.R, R.T.).
¹⁰ Division of Genetic Medicine, Department of Medicine (M.M.S., J.N.H.), Vanderbilt University Medical Center, Nashville, TN.
¹¹ Division of Quantitative Sciences, Department of Obstetrics and Gynecology (D.R.V.E., A.G.), Vanderbilt University Medical Center, Nashville, TN.
¹² Department of Biomedical Informatics (D.R.V.E.), Vanderbilt University Medical Center, Nashville, TN.
¹³ Institute of Medicine and Public Health (D.R.V.E., T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
¹⁴ Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Nashville (C.L.R.).
¹⁵ VA Palo Alto Health Care System (P.S.T.).
¹⁶ Department of Medicine, Stanford University School of Medicine, CA (P.S.T.).
¹⁷ Stanford Cardiovascular Institute (P.S.T.).
¹⁸ VA Boston Healthcare System, MA (J.M.G.).
¹⁹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.M.G., C.J.O.).
²⁰ Epidemiology and Genomic Medicine, Atlanta VAMC, Decatur, GA (P.W.F.W.).
²¹ Cardiology Division, Emory School of Medicine, Atlanta, GA (P.W.F.W.).
²² VA Boston Healthcare System, Section of Cardiology (C.J.O.).
²³ Division of Epidemiology, Department of Medicine (T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
²⁴ Memphis VA Medical Center, TN (C.P.K.).
²⁵ University of Tennessee Health Science Center, Memphis (C.P.K.).
²⁶ Vanderbilt Precision Nephrology Program (A.M.H.), Vanderbilt University Medical Center, Nashville, TN.

PMID: 34148359
PMCID: PMC8364328
DOI: 10.1161/HYPERTENSIONAHA.120.16181

Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program

Elvis A Akwo et al. Hypertension. 2021 Aug.

. 2021 Aug;78(2):376-386.

doi: 10.1161/HYPERTENSIONAHA.120.16181. Epub 2021 Jun 21.

Authors

Affiliations

¹ Division of Nephrology and Hypertension, Department of Medicine (E.A.A., C.R.-C., T.A.I., O.D.W., E.D.S., A.M.H.).
² Vanderbilt Center for Kidney Disease (E.A.A., C.R.-C., T.A.I., E.D.S., A.M.H.).
³ Tennessee Valley Healthcare System, Nashville, VA (E.A.A., C.R.-C., C.P.C., S.C.S., T.A.I., O.D.W., E.D.S., A.M.H.).
⁴ Division of Rheumatology, Department of Medicine (C.P.C.), Vanderbilt University Medical Center, Nashville, TN.
⁵ Vanderbilt Genetics Institute (C.P.C., A.G., R.T.).
⁶ Division of Gastroenterology, Hepatology and Nutrition (S.C.S.), Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Medicine (N.J.B., J.M.L.), Vanderbilt University Medical Center, Nashville, TN.
⁸ Yale School of Medicine, New Haven, CT (N.J.B.).
⁹ Department of Biostatistics, Vanderbilt School of Medicine (B.X.R, R.T.).
¹⁰ Division of Genetic Medicine, Department of Medicine (M.M.S., J.N.H.), Vanderbilt University Medical Center, Nashville, TN.
¹¹ Division of Quantitative Sciences, Department of Obstetrics and Gynecology (D.R.V.E., A.G.), Vanderbilt University Medical Center, Nashville, TN.
¹² Department of Biomedical Informatics (D.R.V.E.), Vanderbilt University Medical Center, Nashville, TN.
¹³ Institute of Medicine and Public Health (D.R.V.E., T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
¹⁴ Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Nashville (C.L.R.).
¹⁵ VA Palo Alto Health Care System (P.S.T.).
¹⁶ Department of Medicine, Stanford University School of Medicine, CA (P.S.T.).
¹⁷ Stanford Cardiovascular Institute (P.S.T.).
¹⁸ VA Boston Healthcare System, MA (J.M.G.).
¹⁹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.M.G., C.J.O.).
²⁰ Epidemiology and Genomic Medicine, Atlanta VAMC, Decatur, GA (P.W.F.W.).
²¹ Cardiology Division, Emory School of Medicine, Atlanta, GA (P.W.F.W.).
²² VA Boston Healthcare System, Section of Cardiology (C.J.O.).
²³ Division of Epidemiology, Department of Medicine (T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
²⁴ Memphis VA Medical Center, TN (C.P.K.).
²⁵ University of Tennessee Health Science Center, Memphis (C.P.K.).
²⁶ Vanderbilt Precision Nephrology Program (A.M.H.), Vanderbilt University Medical Center, Nashville, TN.

PMID: 34148359
PMCID: PMC8364328
DOI: 10.1161/HYPERTENSIONAHA.120.16181

Abstract

[Figure: see text].

Keywords: Treatment-resistant hypertension; apolipoprotein L1 variants; end-stage kidney disease; myocardial infarction; race; stroke.

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Figures

**Figure 1:**
Effect of apparent treatment resistant hypertension (ATRH) on the risk of incident ESKD, MI and stroke among hypertensive Veterans in the Million Veteran Program. After full adjustment for baseline covariates, compared to NRH, ATRH was associated with an 85%, 65% and 81% higher risk of incident ESKD, MI and stroke respectively. Abbreviations: ATRH, apparent treatment resistant hypertension; ESKD, end-stage kidney disease; MI, myocardial infarction; NRH, non-resistant hypertension.

**Figure 2**
A. Excess incidence of incident ESKD due to interaction between ATRH and race. In the absence of interaction, the expected incidence rate (per 1000PY) among blacks with ATRH would be the sum of the background incidence (0.63), incidence due to ATRH alone (1.27) and incidence related to black race (1.90). However, the observed incidence (5.69) was greater than the expected (3.80); which is suggestive of synergistic additive interaction between ATRH and black race for the association with incident ESKD. The excess incidence due to interaction (dark orange bar) represents an excess of 189 incident ESKD cases per 100, 000PY among blacks with ATRH. Abbreviations: ATRH, apparent treatment resistant hypertension; ESKD, end-stage kidney disease; NRH, non-resistant hypertension; PY, person-years. B. Relative excess risk of incident ESKD due to interaction between ATRH and race. The Y-axis represents the incidence rate ratio (IRR) for ESKD comparing whites with ATRH, blacks with NRH, blacks with ATRH to the referent group (whites with NRH). The relative excess risk due to interaction (RERI) between ATRH and race = IRR₁₁ - IRR₁₀ - IRR₀₁ + 1 = 3.00 (95%CI: 1.79, 4.21); and is represented by the dark orange bar as in Figure 2A. The attributable proportion (AP) = RERI/IRR₁₁ = 33.2 (95%CI: 23.6, 42.7) suggesting that 33.2% of the risk of incident ESKD among blacks with ATRH is due to the synergistic interaction between ATRH and race. Abbreviations: ATRH, apparent treatment resistant hypertension; ESKD, end-stage kidney disease; NRH, non-resistant hypertension.

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References

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Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program

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Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program

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