The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease (CKD). We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in non-dialysis CKD patients. ATRH was defined as blood pressure (BP) ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with BP at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male gender, black race, diabetes, and higher BMI were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events compared to participants without ATRH - composite of myocardial infarction (MI), stroke, peripheral arterial disease (PAD), congestive heart failure (CHF), and all-cause mortality HR [95% CI]: (1.38 [1.22,1.56]); renal events (1.28 [1.11, 1.46]); CHF (1.66 [1.38, 2.00]); and all-cause mortality (1.24 [1.06,1.45]). The subset of participants with ATRH and BP at goal on ≥ 4 medications also had higher risk for composite of MI, stroke, PAD, CHF, and all-cause mortality HR [95% CI] (1.30 [1.12, 1.51]) and CHF (1.59 [1.28, 1.99]) compared to those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with eGFR ≥30 ml/min/1.73 m2. Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with CKD. This underscores the need for early identification and management of patients with ATRH and CKD.

Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD). We analyzed the association of inflammatory biomarkers with ATRH and its complications in CKD patients. ATRH was defined as blood pressure (BP) ≥140/90 mm Hg while taking ≥3 antihypertensive medications or BP <140/90 mm Hg while taking ≥4 medications. Analyses included 1,359 Chronic Renal Insufficiency Cohort (CRIC) Study participants with ATRH and 2,008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite CVD and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% confidence intervals [CI]) of ATRH for the highest tertile vs. lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for interleukin-6 (IL-6), 1.49 (95% CI, 1.20-1.85) for tumor necrosis factor-α (TNF-α) and 0.77 (95% CI, 0.63-0.95) for transforming growth factor-β (TGF-β). High-sensitivity C-reactive protein, fibrinogen, interleukin-1β, and interleukin-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with CVD and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-β were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve BP control in CKD patients.