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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Circulation. Author manuscript; available in PMC 2012 August 30.
Published in final edited form as:
PMCID: PMC3210066
NIHMSID: NIHMS317181

Uncontrolled and Apparent Treatment Resistant Hypertension in the U.S. 1988–2008

Abstract

Background

Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure (BP) control.

Methods and Results

Subjects included 13,375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANES) subdivided into 1988–1994, 1999–2004, 2005–2008. Uncontrolled hypertension was defined as BP ≥140/≥90 mmHg and apparent treatment resistant (aTRH) when subjects reported taking ≥3 antihypertensive medications. Framingham 10-year coronary risk (FCR) was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1–2 BP medications, and aTRH across all three survey periods. More than half of uncontrolled hypertensives were untreated across surveys including 52.5% in 2005–2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthcare visits (0–1/yr), body mass index <25 kg/m2, absence of chronic kidney disease (CKD), and FCR <10% (p<0.01). Most treated, uncontrolled patients reported taking 1–2 BP medications, a proxy for therapeutic inertia. This group was older, had higher FCR than patients controlled on 1–2 medications (p<0.01), and comprised 34.4% of all uncontrolled and 72.0% of treated uncontrolled patients in 2005–2008. Apparent TRH increased from 15.9% (1998–2004) to 28.0% (2005–2008) of treated patients, p<0.001. Clinical characteristics associated with aTRH included ≥4 visits/yr, obesity, CKD and FCR >20% (p<0.01).

Conclusions

Untreated, under-treated, and aTRH patients have consistent characteristics that could inform strategies to improve BP control by decreasing untreated hypertension, reducing therapeutic inertia in under-treated patients, and enhancing therapeutic efficiency in aTRH.

Keywords: Hypertension, high blood pressure, hypertension control, antihypertensive medications, treatment resistant hypertension, demographic differences

Introduction

Blood pressure control to <140/<90 mmHg among a representative sample of hypertensive patients participating in National Health and Nutrition Examination Surveys improved from 27.3% in 1988–1994 to 50.1% in 2007–2008.1,2 Based on NHANES 2007–2008 hypertension prevalence data and estimates of the U.S. population ≥18 years old in 2008, there are approximately 67.5 million hypertensive adults in the U.S., with over 33 million uncontrolled.2,3 Approximately 13 of the 33 million uncontrolled hypertensive patients are unaware and 20 million aware of their hypertension.

Data from NHANES 1988–2008 documents that the majority of uncontrolled hypertensive patients remain untreated.2 Other evidence suggests that therapeutic inertia, i.e., the failure to up-titrate or add antihypertensive medications when blood pressure is uncontrolled, is a significant contributor to uncontrolled hypertension.4-6 Moreover, the prevalence of treatment resistant hypertension, i.e., blood pressure uncontrolled on a rational regimen including ≥3 or controlled on ≥4 antihypertensive medications, appears to be increasing. This may reflect the effects of an aging population with more obesity and related comorbidities, e.g., diabetes mellitus and chronic kidney disease.7

Defining the clinical characteristics of hypertensive patients with untreated, inadequately treated, and treatment resistant hypertension could inform strategies and interventions for improving blood pressure management. Therefore, the National Health and Nutrition Examination Survey (NHANES) 1988–2008 were analyzed. While medication dose and adherence as well as blood pressure measurement artifacts are also significant factors in defining inadequately treated and treatment resistant hypertension,7 NHANES does not capture these variables. Thus, the term apparent treatment resistance hypertension (aTRH) is applied.

Methods

As described previously,2 NHANES 1988–1994 and 1999–2008 were conducted by the Centers for Disease Control and Prevention National Center for Health Statistics (NCHS). NHANES volunteers were selected using stratified, multistage probability sampling of the non-institutionalized U.S. population. All adults provided written informed consent approved by the NCHS Institutional/Ethics Review Board.8,9

Definitions

Race/ethnicity was determined by self report and separated into non-Hispanic white (white), non-Hispanic black (black), and Hispanic ethnicity of any race as described.1,2,10 While other race data were obtained (American Indian, Alaskan Native, Asian or Pacific Islander and other race not specified), the number of individuals was insufficient for meaningful analyses.2

Blood pressure (BP) measurement methods were consistent across 1988–1994 and 1999–2008.2 In brief, BP was measured by trained physicians using a mercury sphygmomanometer and appropriately sized arm cuff on subjects after five minutes seated rest. Individuals without recorded BP were excluded. In determining mean systolic and diastolic BP for individuals, the first BP value was used if only one measurement was obtained. The second BP was used if two readings were taken; the second and third values were averaged when available. More than 90% of subjects had ≥2 BP measurements in all survey periods.2

Defining hypertension

Hypertension was defined as mean systolic BP ≥140 and/or mean diastolic BP ≥90 mmHg and/or a positive response to the question “Are you currently taking medication to lower your BP?”1,2,10 Awareness of hypertension was determined by hypertensive patients responding affirmatively to the question, “Have you ever been told by a doctor or other healthcare professional that you had hypertension, also called high BP?”1,2,10 Treatment of hypertension was established by participants responding “Yes” to the question, “Because of your hypertension/high BP are you now taking prescribed medicine?”1,2,10

Control of hypertension was defined as BP <140/<90 mmHg across all survey periods, although the BP goals for high risk subgroups including diabetics was lower for 1999–2008. 1994.11-14 Recent evidence does not clearly support a goal systolic BP <140 for diabetic patients or those with non-proteinuric hypertensive renal disease.15,16 For these reasons and to facilitate comparisons across study, this report focuses exclusively on goal BP <140/<90.

Concomitant risk factors including diabetes and cigarette smoking were defined as described.2 Definitions for cardiovascular disease (CVD) including stroke and coronary heart disease (CHD) were described.2 Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/m2/min and/or urine albumin:creatinine ≥300 mg/g.17,18 Serum creatinine values were adjusted to facilitate comparisons of eGFR across surveys.19

Diabetes mellitus

Diabetes was defined by a positive response to the questions, “Have you ever been told by a doctor that you have diabetes?”, and/or “Are you now taking insulin?”, and/or “Are you now taking diabetes pills to lower your blood sugar?” The definition did not include patients with only fasting plasma glucose ≥126 mg/dL, i.e. “undiagnosed diabetes”.20,21

Low-density lipoprotein cholesterol (LDL-C)

LDL-C, calculated using the Friedewald equation,22 was obtained from the NHANES dataset for the three time periods.

Framingham 10-year CHD risk was calculated.22

Number of medical visits in the past year was assessed by the question, “how many times did you receive healthcare over the last year”? The responses were grouped in three categories including 0–1, 2–3, and ≥4 healthcare visits/year.

Insurance status

Insurance status is determined by a Yes/No answer to the question “Are you covered by health insurance or some other kind of health care plan?”

Therapeutic inertia (TI) was calculated for uncontrolled patients that reported ≥2 healthcare visits/yr. Uncontrolled patients reporting 0–1 visits annually were excluded as infrequent care provides little opportunity to intensify treatment. TI was arbitrarily defined as high, moderate, low, and none based on the number of antihypertensive medications reported, BP, and 10-year Framingham CHD risk.

High level therapeutic inertia included patients on 0–1 antihypertensive medications with BP (i) ≥160/≥100 irrespective of 10-yr CHD risk (ii) ≥150/≥95 and <160/<100 with 10-year CHD risk 10–20% and >20% (iii) ≥140/≥90 and <150/<95 with 10-year CHD risk ≥20%.

Moderate level therapeutic inertia included patients on 2 medications with BP (i) ≥160/≥100 irrespective of 10-yr CHD risk (ii) ≥150/≥95 and <160/<100 with 10-year CHD risk 10–20% and >20% (iii) ≥140/≥90 and <150/<95 with 10-year CHD risk ≥20% as well as (c) patients on 0–1 meds with BP (i) ≥150/≥95 and <160/<100 with 10-yr CHD risk <10% (ii) ≥140/≥90 and <150/<95 with 10-year CHD risk 10–20%.

Low level therapeutic inertia included patients on 2 meds with BP (i) ≥150/≥95 and <160/<100 with 10-yr CHD risk <10% (ii) ≥140/≥90 and <150/<95 with 10-year CHD risk 10–20% as well as patients with BP ≥140/≥90 and <150/<95 on 0–1 medications and 10-yr risk <10%. No therapeutic inertia included patients with BP ≥140/≥90 and <150/<95 on 2 medications and 10-yr risk <10% and all uncontrolled patients on ≥3 BP medications.

Antihypertensive medications

Participants were asked if they had taken any prescription medications in the past month. During the household surveys in 1999–2004 and 2005–2008, participants were requested to provide prescription containers and 88.8% and 88.3%, respectively, did so. Each medication identified from medications provided or described was recorded and matched to a prescription drug database. Each medication identified was assigned its generic equivalent. Antihypertensive medications were classified to a single category according to the Seventh Report of the Joint National Committee on Hypertension with addition of proprietary medications not marketed when the document was published.14 Single-pill combinations were separated into their generic components. Each medication was classified to only one category. The sum of BP medication categories defined the number of antihypertensive medications taken by each patient.

Data analysis

The NHANES Analytic and Reporting Guidelines were followed.23 SAS callable SUDAAN version 9.0.1 (Cary, NC) was used for all analyses to account for the complex NHANES sampling design. Standard errors were estimated using Taylor series linearization. All NHANES periods were age-adjusted to the U.S. 2000 census data as described.2

To test for significant differences in variables between/among groups within each survey, the Chi-Square test in the CROSSTAB procedure was used for categorical variables; WALD F test in the REGRESS was used for continuous variables, and LOGLINK was used for medications. When more than two groups were compared within an NHANES survey period, analysis was limited to assessing differences across the groups and not between pairs. Pair-wise comparisons between the three NHANES periods were conducted using t-tests of weighted means1 between pairs of the three groups matched for medication number. The effects of time were not assessed before pair-wise comparisons as SUDAAN would not allow this function when only three time periods were analyzed. Since multiple statistical comparisons were performed within and between the three NHANES time periods, two-sided p-values <0.01 were accepted as statistically significant.

Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship of selected independent clinical covariables to three dependent variables including untreated, uncontrolled hypertension, uncontrolled hypertension treated with 1–2 BP medications and uncontrolled aTRH treated with ≥3 BP medications. Univariable and fully adjusted multivariable logistic regressions were performed using RLOGIST.

Results

Uncontrolled and controlled hypertensive patients (Table 1)

The proportion of patients with uncontrolled hypertension declined from 73.2% in 1988–1994 to 52.5% in 2005–2008. Men were more likely than women to have uncontrolled hypertension in 1988–1994 and 2005–2008. Across surveys, a lower proportion of Whites and a higher proportion of Blacks and Hispanics of any race were represented among uncontrolled patients. As expected, systolic and diastolic BP values were lower in controlled than uncontrolled patients. Systolic BP did not change over time in either group, whereas diastolic BP declined in both.

The number of BP medications increased over time in both treated uncontrolled and controlled patients but did not differ between groups. Uncontrolled patients were more likely to report 0–1 healthcare visits annually, whereas controlled patients were more likely to report ≥4. The proportion of uninsured patients did not change in controlled hypertensives but increased in uncontrolled patients over time. Body mass index rose over time in both groups and was higher in controlled patients. LDL-cholesterol declined over time in both groups and was lower in controlled patients in 1999–2004 and 2005–2008. The prevalence of diabetes mellitus increased over time and was more common in controlled than uncontrolled patients. The percentage of current cigarette smokers did not differ between controlled and uncontrolled hypertensives but was lower among uncontrolled patients in 1999–2004 than the other two time periods.

The percentage of hypertensive patients with CKD did not change significantly with time and was not different in uncontrolled than controlled patients. Prevalent clinical CVD was more common in controlled than uncontrolled patients in 1988–1994 and 1999–2004 but did not change with time. Framingham ten-year CHD risk was higher in controlled than uncontrolled patients in 1988–1994 and 1999–2004.

Table 1
Characteristics of uncontrolled and controlled individuals with hypertension in three NHANES time periods.

Antihypertensive medication number

The percentage of all hypertensive individuals that were untreated declined, while the percentage on two and ≥3 BP medications increased over time (Figure 1[A]). Among all uncontrolled patients, the percentage of untreated subjects declined with time but the mean remained >50% in 2005–2008 (52.2%, 95% confidence interval [CI] 48.1–56.3% [Figure 1[B]). The percentage of treated uncontrolled patients on 1 medication fell, whereas those on ≥3 medications rose with time (Figure 1[C]). Among treated uncontrolled [1C] and treated controlled hypertensive patients [1D], the number of BP medications reported and changes over time were similar. The proportion on one BP medication fell, and those on ≥3 BP medications rose. All controlled hypertensives reported taking BP medications. However, ~4–5% of them did not bring any antihypertensive medications to the examination, nor did they identify any BP medications during the interview including ‘unspecified’ (Figure 1[D]).

Figure 1
The percentages are depicted of hypertensive patients that reported taking 0, 1, 2, and ≥3 antihypertensive medications for (A) all (B) all uncontrolled (C) treated uncontrolled (D) treated controlled patients in the different NHANES. Symbols ...

Uncontrolled hypertensive patients grouped by number of antihypertensive medications (Table 2)

The proportion of untreated patients fell between 1988–1994 and 2005–2008, whereas the percentage on 1–2 medications did not change and the percentage on ≥3 medications rose. The proportion of uncontrolled hypertensive patients who were uninsured increased with time. Systolic BP was lower and diastolic BP higher in untreated than treated patients. Untreated hypertensive patients were younger and more likely to be men, infrequent healthcare users, uninsured and to have 10-yr CHD risk <10% than treated patients. Conversely, untreated patients were less likely to have ≥4 healthcare visits annually, Stage 2 hypertension, diabetes mellitus, CKD and 10-yr CHD risk >20% than treated patients, especially those on ≥3 BP medications, i.e., apparent treatment resistant hypertension (aTRH).

Table 2
Characteristics of uncontrolled hypertensive patients grouped by number of antihypertensive medications reportedly taken.

Controlled hypertensive patients grouped by number of antihypertensive medications (Table 3)

In general, there were more differences by number of medications within uncontrolled than within controlled hypertensive patients. While all controlled hypertensive patients reported taking BP medication, 4–5% across all survey periods did not verbally identify or physically bring any of them during their assessment. Untreated hypertensive patients were younger than those on ≥3 medications. Framingham 10-yr CHD risk generally increased with the number of medications with significant differences in 1999–2004 and 2005–2008. The percentage of controlled hypertensive patients on ≥4 medications was 2.3% [1.3%–3.3%] in 1988–1994, 5.2% [3.6%–6.8%] in 1999–2004, and 7.3% [5.1%–9.4%] in 2005–2008

Table 3
Characteristics of controlled hypertensive patients grouped by number of antihypertensive medications reportedly taken.

Therapeutic inertia in uncontrolled hypertensive patients with ≥2 healthcare visits annually (Table 4)

Using the definition provided in Methods, the percentage of patients with no therapeutic inertia rose with time over the three NHANES periods, whereas the percentage of patients with high level therapeutic inertia declined. Nevertheless, more than half of uncontrolled hypertensive patients in all time periods had a moderate or high level of therapeutic inertia.

Table 4
Therapeutic inertia among uncontrolled hypertensive patients in three NHANES survey periods.

Classes of antihypertensive medications (Table 5)

The class of antihypertensive medications reported by controlled and uncontrolled hypertensive patients taking 1, 2 and ≥3 such medications is provided for each of the three NHANES periods. The NHANES databases do not indicate the order antihypertensive agents were added for patients that reported taking 2 and ≥3 BP medications. In all time periods, ACE inhibitors, beta-blockers and CCBs were the agents most often reported by controlled and uncontrolled hypertensive patients reportedly taking a single antihypertensive medication. Diuretics, especially thiazide-type diuretics, showed the largest increase in percentage utilization as BP medication number rose from one to three or more. There were a limited number of differences significant at p<0.01 level between uncontrolled and controlled hypertensive patients that reported taking each class of medication in the three NHANES time periods. Non-dihydropyridine calcium antagonists were the class of antihypertensive medication class with the largest number of significant differences between controlled and uncontrolled patients and were taken more often by those who were uncontrolled.

Table 5
Antihypertensive medication classes prescribed to controlled and uncontrolled hypertensive patients by medication number.

Untreated hypertension (Figure 2)

By multivariable logistic regression, the clinical variables consistently and independently associated with untreated hypertension across the three NHANES periods included male sex, patients with 0–1 healthcare visits/yr, BMI <25 kg/m2, Stage <3 CKD, and 10-year FCR 10–19% and <10% compared to the reference groups.

Figure 2
The independent relationship between selected clinical variables and the dependent variable untreated hypertension are shown as multivariable odds ratios and 95% confidence intervals for each of the three NHANES periods. The reference group for comparison ...

Uncontrolled hypertension on 1–2 BP medications (Figures 3)

All of the independent variables shown in Figures 3 and and44 were examined simultaneously in multivariables logistic regression analysis. The clinical variables independently associated with uncontrolled hypertension on 1–2 BP medications included male sex (1999–2004, 2005–2008), black race (1988–1994, 1999–2004), age and 10-year CHD risk >20% (all time periods). Patients on thiazide-type diuretics (1988–1994, 1999–2004) and angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (1999–2004, 2005–2008) were less likely to have hypertension uncontrolled on 1–2 BP medications. In contrast, patients reportedly taking non-dihyrdropyridine calcium channel blockers (CCBs) were more likely to have treated, uncontrolled hypertension (1988–1994, 2005–2008).

Figure 4
The independent relationship between selected clinical variables and the dependent variable apparent treatement resistant hypertension (aTRH, [uncontrolled on ≥3 BP medications]) are shown as multivariable odds ratios and 95% confidence intervals ...
Figure 3Figure 3
The independent relationship between selected clinical variables including class of antihypertensive medications and the dependent variable uncontrolled hypertension on 1–2 antihypertensive medications are shown as multivariable odds ratios and ...

Clinical factors independently associated with aTRH among all uncontrolled patients (Figure 4)

In all time periods, patients reporting ≥4 healthcare visits annually were more likely to have aTRH, i.e.,uncontrolled on ≥3 BP medications. Other clinical factors consistently and independently associated with aTRH in multivariable logistic regression included obesity, CKD and 10-year CHD risk >20%. Increasing age and black race were independently linked with aTRH in 2005–2008, and patients with 10-yr CHD risk 10–20% were more likely to have TRH in 1988–1994 and 1999–2004.

No significant differences were seen in the percentages of controlled and uncontrolled hypertensive patients taking various classes of antihypertensive medications in 2005–2008 with one exception (Figure 5). Non-dihyrdropyridine calcium channel blockers were taken more often by uncontrolled than controlled hypertensive patients.

Figure 5
The percentage of controlled and uncontrolled hypertensive patients taking various classes of antihypertensive medications are depicted for NHANES 2005–2008 only. The percentages of patients within each bar are further subdivided by those who ...

Discussion

The proportion of hypertensive patients with blood pressure ≥140 systolic and/or ≥90 diastolic declined from 73.2% in 1988–1994 to 52.5% in 2005–2008, p<0.001 (Table 1, Figure 1).1,2 Despite progress, more than 30 million hypertensive patients remain uncontrolled in the U.S. The primary objective of this study was to identify consistent characteristics and trends that distinguished uncontrolled from controlled hypertensive patients. The study focused on pursuing this objective in three groups of uncontrolled patients; namely, those that are untreated and those reportedly taking 1–2 and ≥3 blood pressure medications.

Untreated hypertension

Hypertension treatment increased steadily from 1988–2008,1,2,10 yet more than half of uncontrolled patients were untreated in the three NHANES periods. While hypertension awareness improved over the same time period, roughly 2/3 of untreated patients in all surveys were unaware (Table 2). Patient characteristics independently associated with untreated hypertension, including both unaware and aware patients, across the three NHANES periods included male sex, infrequent healthcare, lean body mass indices, absence of CKD and 10-yr Framingham CHD risk (FCR) <10% and 10–20% (Figure 2), i.e., better cardiovascular and renal health. Infrequent healthcare emerged as a major issue, since a mean of 40% or more of untreated hypertensive patients in all survey periods had 0–1 healthcare visits annually. Lack of insurance is a factor limiting healthcare use, irrespective of income.24 Uninsured status is rising with time among uncontrolled patients (Table 1) and was independently linked with untreated hypertension in two of three NHANES periods (Figure 2), an association noted previously.25

The findings among untreated hypertensive patients suggest that increasing healthcare utilization in traditional or non-traditional settings, e.g., worksites,26 is critical in reducing the burden of untreated hypertension. Raising the perceived value of regular preventive healthcare services among those without clinically overt disease emerges as an important complementary educational strategy. Screening efforts to raise hypertension awareness, especially among medically underserved groups and individuals at lower risk, should include inquiries on regular use of a medical home and plans to engage infrequent and non-users in ongoing primary care. Initiatives to reduce the growing number of uninsured adults also emerge as important in addressing the substantial burden untreated, uncontrolled hypertension.

Focus on uncontrolled hypertension treated with 1–2 BP medications

Approximately one-third of all uncontrolled patients reported taking 1–2 antihypertensive medications in all three NHANES periods. However, among treated uncontrolled patients the proportion on 1–2 medications fell (Table 3). One logical option for improving BP control in this comparatively large group of uncontrolled patients is an additional antihypertensive medication. Clinical variables independently linked to uncontrolled hypertension on 1–2 BP medications included increasing (older) age and 10-yr FCR >20% in all three time periods and male sex, Hispanic ethnicity and infrequent healthcare in two NHANES periods (Figure 3).

The comparatively higher risk among uncontrolled than controlled hypertensive patients on 1–2 medications provides further justification for adding a second or third antihypertensive medication to improve BP control. Their mean systolic BP was >150 mmHg across surveys with many having Stage 2 hypertension, which should also prompt treatment intensification. While infrequent healthcare was a distinguishing characteristic of treated, uncontrolled hypertension on 1–2 BP medications, roughly 85–90% of this group had two or more healthcare visits annually. Thus, the majority appear to be seen sufficiently frequently to allow treatment intensification.

Our previous work identified therapeutic inertia as a significant contributor to uncontrolled hypertension, accounting for ~19% of the total variance in BP control.5 While the NHANES database does not include information required to calculate therapeutic inertia,4,5 it was arbitrarily defined based on BP, number of antihypertensive medications, and 10-year CHD risk. While high level therapeutic inertia declined with time (Table 1), therapeutic inertia was high or moderate in more than half of uncontrolled hypertensives who reported two or more healthcare visits annually in all three NHANES periods (Table 4). Therapeutic inertia is not a provider only trait but appears to reflect a patient-provider interaction.5 In addition to provider interventions to reduce therapeutic inertia, educating patients, especially those at higher risk, on the importance of BP control may facilitate efforts to overcome therapeutic inertia.

The data also suggest medication selection affects control. Patients uncontrolled, as compared to controlled, on 1–2 BP medications were less likely to report taking a diuretic in (1988–1994, 2005–2008) and less likely to report an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (1999–2004, 2005–2008). The findings align with the efficacy of diuretics and renin-angiotensin system blockers, especially in combination, for BP control.27 While significant only in 2005–2008, non-dihydropryidine calcium channel blockers (CCBs) may also improve BP control, consistent with the antihypertensive efficacy of non-dihydropyridine CCB as monotherapy and in combination with ACE inhibitor combinations.14,28

Focus on apparent treatment resistant hypertension (aTRH)

The proportion of treated uncontrolled hypertensive patients reportedly taking ≥3 BP medications increased from 15.9% in 1988–1994 to 28.0% in 2005–2008 (Table 3, Figure 1C). These patients appear to have treatment resistant hypertension, although 30–50% may have pseudo-hypertension, which includes non-adherence, inaccurate measurements and artifacts, e.g., office or white-coat effect.7,29 While our report focused on uncontrolled aTRH, the American Heart Association Position Statement also identified patients with controlled hypertension taking ≥4 medications as treatment resistant.7 Using this definition and data presented in Tables and Results, 11.8% of all hypertensive patients in 2005–2008 have aTRH, an increase from 5.5% in 1988–1994 and 8.5% in 1999–2004.

In multivariable analysis, clinical factors independently linked with uncontrolled aTRH across surveys included frequent healthcare use (≥4 healthcare visits annually), which indicates the medical community has numerous opportunities to improve their BP control. The patients with aTRH are further characterized by obesity, CKD, and 10-year FCR >20% (Figure 4). In 2005–2008, older age and black race and in 1999–2004 female sex emerged as independent clinical correlates of aTRH. The clinical factors independently associated with aTRH identified are consistent with characteristics previously cited.7 Patients with aTRH are generally at significant risk for cardiovascular disease and likely to benefit from better BP control.

Limited effectiveness of current antihypertensive medications and strategies for combining them constitute a barrier to better hypertension control. Of particular note was the infrequent use of aldosterone antagonists among patients with aTRH (Table 5, Figure 5). Several trials indicate that addition of an aldosterone antagonist lowers BP 20–25/10–15 mmHg in patients with treatment refractory and resistant hypertension.30,31 More effective antihypertensive medications or strategies for combining them are urgently needed as the burden of treatment resistant hypertension is likely to grow given an aging population with more obesity and related complications including diabetes as CKD. Personalized medicine including hemodynamic and renin-guided therapeutics32,33 as well as genetic testing34 offer alternative or complementary approaches to constructing more effective medication regimens for treatment resistant patients.

This study has limitations. While NHANES represents the non-institutionalized civilian U.S. population, the sample size is relatively small. Thus, not all clinically and epidemiologically important differences may be detected. Second, medications were determined by self report, which may be inaccurate, although >85% of hypertensive patients brought their medications to the 1999–2004 and 2005–2008 examinations. Adherence was not assessed and medication dose and frequency were not recorded. Third, hypertension was defined by blood pressure on a single visit. Thus, hypertension status may have been incorrectly assigned to some patients, especially the unaware, untreated subset, which had lower blood pressures than uncontrolled treated patients. Fourth, while lifestyle change is also important to blood pressure control, our analysis focused on treatment. Fifth, sample size, while substantial, is comparatively small for subgroup analyses, which increases the potential for falsely accepting the null hypothesis, i.e., no differences between groups. Although appropriate for the large number of statistical comparisons performed in the analysis, the concern of limited power is exacerbated by recognizing statistical significance only when p-values were <0.01.

Despite limitations, our analyses of a nationally representative hypertensive patient sample from three NHANES periods suggest that national efforts to increase healthcare insurance and use of a primary care medical home could further improve hypertension awareness and treatment leading to higher control rates. These efforts are important for untreated, uncontrolled hypertensive patients who are more often men, non-obese, and without overt cardiovascular and renal diseases. Uncontrolled hypertensive patients on 1–2 BP medications could benefit from an additional antihypertensive medication. These patients are generally seen sufficiently frequently to have therapy intensified. They are older and have greater risk for coronary heart disease than their controlled counterparts taking 1–2 BP medications, i.e., there appear to be compelling reasons to intensify therapy. This group is also more likely to include men, blacks and Hispanics and to have Stage 2 hypertension, although these characteristics were not significant in all time periods. Interventions to reduce therapeutic inertia, which should include efforts directed at both providers and patients, could be useful for improving their BP control and reducing risk.

A growing proportion of hypertensive patients appear treatment resistant. Strategies to enhance therapeutic efficacy and to promote therapeutic adherence and lifestyle change are especially important for this group. Trends toward an older and more obese population with a higher prevalence of diabetes and CKD could lead to a growing burden of treatment resistant hypertension.7 To counter these potentially adverse trends and improve overall hypertension control, integrated healthcare research, policy and delivery initiatives are needed to reverse growth in unhealthy lifestyles and obesity,35,36 enhance regular use of a medical home, reduce therapeutic inertia, develop more efficacious antihypertensive agents, and improve methods for selecting effective antihypertensive combinations for individual patients.

Acknowledgments

None.

Funding Sources: This work was supported in part by the State of South Carolina (Hypertension Initiative), NIH R01 National Heart, Lung and Blood Institute HL07080684, NIH R01 National Institute of Diabetes and Digestive and Kidney Diseases DK067615, NIH R01 National Institute of Neurological Disorders and Stroke NS058728 and United States Army, W81XWH-10-2-0057. The funding agencies were not involved in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review or approval of the manuscript.

Footnotes

Conflict of Interest Disclosures: Brent M. Egan. Grant support: Daiichi-Sankyo (>$50,000), Novartis (>$50,000), Takeda (>$50,000); Lecturer with honoraria on CME-accredited programs: American Society of Hypertension Carolinas-Georgia-Florida Chapter (>$10,000), International Society of Hypertension in Blacks (<$10,000); Consultant: NicOx (<$10,000).

Yumin Zhao. None

R. Neal Axon. None

Walter A. Brzezinski: None

Keith C. Ferdinand: Speakers’ Bureau at AstraZeneca (<$10,000), Novartis (<$10,000), Forest (<$10,000), and Daiichi-Sankyo (<$10,000); honoraria from AstraZeneca (>$10,000), Novartis (>$10,000), Forest (>$10,000); Consultant/Advisory Board AstraZeneca (<$10,000), Novartis (<$10,000), and Forest (<$10,000).

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