Predicting the risk of apparent treatment-resistant hypertension: a longitudinal, cohort study in an urban hypertension referral clinic.

Apparent treatment-resistant hypertension (aTRH) is associated with higher prevalence of secondary hypertension, greater risk for adverse pressure-related clinical outcomes, and influences diagnostic and therapeutic decision-making. We previously showed that cross-sectional prevalence estimates of aTRH are lower than its true prevalence as patients with uncontrolled hypertension undergoing intensification/optimization of therapy will, over time, increasingly satisfy diagnostic criteria for aTRH. aTRH was assessed in an urban referral hypertension clinic using a 140/90 mm Hg goal blood pressure target in 745 patients with uncontrolled blood pressure, who were predominately African-American (86%) and female (65%). Analyses were stratified according to existing prescription of diuretic at initial visit. Risk for aTRH was estimated using logistic regression with patient characteristics at index visit as predictors. Among those prescribed diuretics, 84/363 developed aTRH; the risk score discriminated well (area under the receiver operating curve = 0.77, bootstrapped 95% CI [0.71, 0.81]). In patients not prescribed a diuretic, 44/382 developed aTRH, and the risk score showed a significantly better discriminative ability (area under the receiver operating curve = 0.82 [0.76, 0.87]; P < .001). In the diuretic and nondiuretic cohorts, 145/363 and 290/382 of patients had estimated risks for development of aTRH <15%. Of these low-risk patients, 139/145 and 278/290 did not develop aTRH (negative predictive value, diuretics - 0.94 [0.91, 0.98], no diuretics - 0.95 [0.93, 0.97]). We created a novel clinical score that discriminates well between those who will and will not develop aTRH, especially among those without existing diuretic prescriptions. Irrespective of baseline diuretic treatment status, a low-risk score had very high negative predictive value.

Influence of albuminuria and glomerular filtration rate on blood pressure response to antihypertensive drug therapy.

BACKGROUND: Albuminuria and glomerular filtration rate (GFR), two factors linked to kidney and vascular function, may influence longitudinal blood pressure (BP) responses to complex antihypertensive drug regimens. METHODS: We reviewed the clinic records of 459 patients with hypertension in an urban, academic practice. RESULTS: Mean patient age was 57-years, 89% of patients were African American, and 69% were women. Mean patient systolic/diastolic BP (SBP/DBP) at baseline was 171/98 mmHg while taking an average of 3.3 antihypertensive medications. At baseline, 27% of patients had estimated (e)GFR <60 ml/min/1.73(2), 28% had micro-albuminuria (30-300 mg/g) and 16% had macro-albuminuria (>300 mg/g). The average longitudinal BP decline over the observation period (mean 7.2 visits) was 25/12 mmHg. In adjusted regression models, macro-albuminuria predicted a 10.3 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 7.9 mmHg lesser longitudinal DBP reduction (p < 0.001); similarly eGFR <60 ml/min/1.73(2) predicted an 8.4 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 4.5 lesser longitudinal DBP reduction (p < 0.001). Presence of either micro- or macro-albuminuria, or lower eGFR, also significantly delayed the time to attainment of goal BP. CONCLUSIONS: These data suggest that an attenuated decline in BP in drug-treated hypertensives, resulting in higher average BP levels over the long-term, may mediate a portion of the increased risk of cardiovascular-renal disease linked to elevated urinary albumin excretion and reduced eGFR.

New salt-sensitivity metrics: variability-adjusted blood pressure change and the urinary sodium-to-creatinine ratio.

DESIGN: We report the results of a 24-week, placebo-controlled, two-period, crossover trial of sodium supplementation in 112 normotensive African Americans, aged 25 to 64 years, with average blood pressure (BP) of 105/70 mm Hg. Estimated 24-hour urinary sodium excretion was 133.6 mmol; the average urinary sodium-to-creatinine ratio was 0.74. METHODS: Variability-adjusted BP change was the difference in BP level after the respective treatment periods, divided by the intra-person standard deviation of the average BP obtained at 3 consecutive screening visits during a 4-week period. RESULTS: The urinary sodium-to-creatinine ratio and the total urine sodium content were 37.8% and 26.5% higher, respectively, at the end of the sodium treatment period. Twenty-four hour ambulatory BP change (mm Hg) (95% CI) was systolic 1.2 (0, 2.4), and diastolic 0.7 (-0.3, 1.8); cuff BP change was systolic 0.9 (-1, 2.9), and diastolic 1.4 (0.1, 2.7). Variability-adjusted BP change was systolic 0.2 (-0.4, 0.8) and diastolic 0.4 (-0.1, 0.9). Though variability-adjusted and unadjusted SBP change correlated highly (r = 0.941, P<.001), only the former correlated with body mass index (r = 0.224, P<.05), a known correlate of salt sensitivity. While total urinary sodium content in timed urine collections and urinary sodium-to-creatinine ratio correlated (r = 0.727, P<.001), neither correlated with cuff BP changes. Change in urinary sodium-to-creatinine ratios of 3 consecutive pooled overnight 8-hour urine collections correlated with changes in 24-hour ambulatory SBP (r = 0.294, P<.001) and DBP (r = 0.193, P<.05); however, change in total urinary sodium content was uncorrelated. Total urinary sodium content of these pooled collections (P = .001), but not the urinary sodium-to-creatinine ratio, was positively related to urinary creatinine excretion per kilogram of body weight, the latter being an indicator of urine collection duration. CONCLUSIONS: The lack of effect of the duration of urine collection on the urinary sodium-to-creatinine ratio is advantageous in individuals who may report inaccurately the duration of their urine collection. Sequential regression analyses demonstrated that the urinary sodium-to-creatinine ratio conveyed all of the changes in urinary sodium excretion information contained in aggregate urinary sodium excretion-and more. Variability-adjusted BP change was the more sensitive metric of BP response to dietary sodium manipulations, than unadjusted BP change. Thus, variability-adjusted BP change and the urinary sodium-to-creatinine ratio appear to be incrementally better metrics of salt sensitivity than those traditionally used.

Relationship of resistant hypertension and treatment outcomes with total arterial compliance in a predominantly African American hypertensive cohort.

Resistant hypertension (RH) affects 8% to 30% of hypertensive patients. Blood pressure (BP) reflects the interaction between vascular compliance, resistance to flow, intravascular volume, and cardiac contractility. The relationship of RH with total arterial compliance index (TACI) has not been adequately explored. The RH period prevalence (RH at baseline or follow-up) was determined in a hypertensive cohort (N=156) and compared across quartiles of TACI. Age- and sex-adjusted systolic BP, diastolic BP, and antihypertensive therapeutic intensity score (TIS) were also determined at the time of first BP control. The cohort was 85.3% African American and 67.3% female. Median follow-up was 7 months. The prevalence of RH at baseline was 14.7% while the period prevalence was 43.6%. The period prevalence of RH by ascending quartile for TACI was 66%, 36.8%, 40%, and 30.8% (P=.008). The average BP and antihypertensive TIS at first BP control across TACI quartiles was 122.3/73.4 mm Hg (2.26), 120.7/72.5 mm Hg (1.88), 122.4/75.3 mm Hg (1.71), and 120.0/79.4 mm Hg (1.64) (P=.62, P=.03, P=.13). Low TACI was linked to higher RH prevalence and antihypertensive TIS at first attainment of goal BP according to the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. TACI provides prognostic information that is clinically and perhaps pathophysiologically relevant in RH.