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J Clin Hypertens (Greenwich). 2012;00:000–000. ©2012 Wiley Periodicals, Inc.
The aim of this study was to test the association of self-reported sleep symptoms to those identified with severe hypertension in a nationally representative sample of adults. Self-reported and study-measured health and sleep characteristics were collected by the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Of 10,526 individuals with completed sleep surveys participating in the study, the authors identified 379 patients with severe hypertension defined as those treated with ≥3 antihypertensive medications including a diuretic; 110 of these had resistant hypertension (RHTN) despite therapy, while 269 were controlled for severe hypertension (CSHTN). Patients with RHTN were more likely to be married, less educated, smoke, and self-report unsatisfactory health and diabetes when compared with patients with CSHTN. Multivariate analyses showed that poorly controlled diabetes (glycated hemoglobin >7%) was the strongest predictor of RHTN (odds ratio, 3.0; 95% confidence interval, 1.2–7.9). Unsatisfactory health (odds ratio, 1.7; 95% confidence interval, 1.7–2.7) was also associated with RHTN. Poorly controlled diabetes and self-reported unsatisfactory heath showed significant association with RHTN. Contrary to expectations, there was no significant association between self-reported snoring/snorting and RHTN, when other factors were examined. The association between poorly controlled diabetes and RHTN warrants further emphasis on strict control of diabetes in these individuals.
Hypertension (HTN) is a highly prevalent chronic condition (29%–31%) in the United States and is reported as insufficiently controlled in up to two thirds of individuals.1,2 Resistant HTN (RHTN) is defined as blood pressure (BP) values in excess of 140/90 mm Hg or 130/80 mm Hg in the presence of diabetes or chronic kidney disease despite treatment with ≥3 antihypertensive medications including a diuretic.3 The prevalence of RHTN in the US adult hypertensive clinic population is estimated to be as high as 15% to 20%.4 Known risk factors associated with RHTN include low socioeconomic status and behavioral factors including a potentially complex medical regimen.5 Obesity, a high-salt diet, physical inactivity, and heavy alcohol intake may alone or in combination contribute to poorly controlled high BPs. In one study that switched from a high- to a low-salt diet was associated with an average reduction in office BP of 23/9 mm Hg in patients with RHTN.6 Hence, identifying and addressing not only nonphysiologic as well as clinically modifiable factors may be important.
The role of sleep symptoms including snoring, snorting, and poor or insufficient sleep in the etiology of RHTN is of interest for a number of reasons. First, obstructive sleep apnea (OSA) or insufficient sleep both commonly present in the population and can be a predictor of future HTN in normotensive individuals.7–9 Second, both OSA and its clinical marker of chronic, frequent snoring have been shown to be associated with RHTN in hospital-based case series; both of these entities are readily treatable.10–12
The National Health and Nutritional Examination Survey (NHANES) was designed as a public health survey tool to detect and monitor disease and illness over time. Questions have been recently added to assess the potential relationships among sleep disorders, sleep duration, sleep quality, and prevalent conditions such as HTN and diabetes. Prior overview surveys found increased risk in hypertensive vs nonhypertensive adults having concurrent sleep disorders with poor or short sleep.13 The current study looks more closely at this database in regard to hypertension control with the aim of assessing whether these same self-reported sleep symptoms predict RHTN in those identified with severe hypertension.
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Of 3306 patients with HTN, there were 379 with severe HTN: 269 with CSHTN and 110 with RHTN. Among RHTN patients, 94 had diabetes or CKD. The descriptive characteristics for the final cohorts are described in Table I. Age, sex, ethnic distribution, PIR, sedentary leisure time, illicit drug usage, obesity, and alcohol use and depression scores did not differ significantly between the two groups. Patients with RHTN were more likely to be married, have a lower education level, be current smokers, have unsatisfactory health, and have poorly controlled diabetes as compared with controls. In addition, they were more likely to have diabetes and poorly controlled diabetes.
Table I. General Characteristics of Severe Hypertension Patientsa According to Hypertension Control Statusb (N=379)
| ||Resistant Hypertensionc (n=110)||Controlled Severe Hypertension (n=269)|
|Mean age, y||67.6±1.2||66.4±1.2|
|Male sex, %||48.5±7.4||42.9±3.5|
|Race (Caucasian), %||75.7±4.0||74.4±4.2|
|Mean poverty income ratio (family income/poverty threshold), %||2.2±0.2||2.5±0.1|
|Low education (<high school graduation), %||39.7±4.2d||27.7±3.5|
|No health insurance, %||2.4±1.4||4.3±1.8|
|Marital status (married or living with partner), %||56.3±6.2d||55.5±4.7|
|Current smoker (serum nicotine >10 ng/mL), %||12.9±4.3d||12.1±2.2|
|Alcohol consumption (alcohol ≥1 time per mo), %||43.9±6.3||50.9±3.8|
|Illegal drugs use (current or former use of marijuana, hashish, cocaine, and/or heroin), %||1.8±1.3||4.8±1.3|
|Mean sedentary leisure time (h per d of TV and computer use for entertainment), %||4.1±0.4||3.8±0.1|
|Unsatisfactory health (self-reported fair or poor health), %||69.6±4.1d||56.0±5.0|
|Overweight/obesity (body mass index ≥25 kg/m2), %||83.6±5.0||75.0±3.4|
|Central obesity (waist circumference >88 cm in women or >102 in men), %||75.6±4.7||66.8±3.9|
|Mean direct high-density lipoprotein, mg/dL||49.8±1.4||50.8±1.2|
|Physician-diagnosed diabetes, %||86.4±4.5d||21.6±3.0|
|Poorly controlled diabetes, % (hemoglobin A1c≥7%)||23.8±5.4d||9.2±1.9|
|Depression (PHQ-9 score≥10), %||15.1±3.1||14.3±2.1|
In relation to sleep characteristics (Table II), there was no difference in any of the surrogate symptom measures of sleep apnea, sleep duration, or insomnia between RHTN and CSHTN groups. History of physician-diagnosed OSA was marginally greater in the RHTN group as compared with the CSHTN group.
Table II. Sleep Characteristicsa of Severe Hypertensionb in Patients According to Hypertension Control Status (N=379)c
| ||Resistant Hypertensiond (n=110)||Controlled Severe Hypertension (n=269)|
|Physician-diagnosed obstructive sleep apnea, %||17.5±2.9e||17.4±3.4|
|Snoring (≥3 times per wk in the past 12 mo), %||45.5±5.3||58.3±4.8|
|Snorting (≥3 times per wk in the past 12 mo), %||15.3±3.1||22.1±3.4|
|Combined symptoms of sleep apnea (snoring or snorting ≥3 times per wk in the past 12 mo), %||49.8±4.9||59.3±4.7|
|Severe symptoms of sleep apnea (snoring or snorting ≥5 times per wk in the past 12 mo), %||36.7±6.9||39.0±4.0|
|Severe combined symptoms of sleep apnea (snoring and snorting ≥5 times per wk in the past 12 mo), %||9.4±3.3||9.9±3.0|
|SHST <7 h per weeknight, %||39.8±4.1||42.0±3.2|
|SHST <6 h per weeknight, %||17.5±4.7||16.1±2.3|
|Mild/moderate insomnia (≥1 sleep disturbance 5–15 times per mo and ≥1 daytime functional impairment), %||37.3±4.4||32.7±4.0|
|Severe insomnia (≥1 sleep disturbance ≥15 times per mo and ≥1 daytime functional impairment), %||10.2±2.8||12.3±3.0|
|Insomnia with SHST <7 h per weeknight (≥1 sleep disturbance ≥5 times per mo and ≥1 daytime functional impairment and with SHST <7 h per weeknight), %||21.7±3.3||21.9±2.9|
Univariate analysis (Table III and Table IV) for the RHTN group revealed that people not completing high school had about 1.7 higher odds (95% confidence interval [CI], 1.1–2.7) of having RHTN. Also, diabetes was associated with 12.8 higher odds (95% CI, 7.4–21.9) and poorly controlled diabetes was associated with 3.1 higher odds (95% CI, 1.3–7.2) of having RHTN compared with CSHTN. The patients who reported poor health had 1.8 times higher odds (95% CI, 1.1–2.8) of having RHTN. The patients who reported snoring more than 3 times per week in the past 12 months trended towards a reduced odds of RHTN (that was marginally significant, odds ratio [OR], 0.6; 95% CI, 0.3–1.0). No other sleep symptoms were found to be significantly associated with RHTN in this cohort.
Table III. Univariate ORs for RHTNa in Patients With Severe Hypertensionb
|Risk Factors||Unadjusted OR (95% CI)||P Value|
|Mean age, y||1.04 (0.9–1.2)||.523|
|Male sex||0.8 (0.4–1.6)||.512|
|Race (Caucasian)||1.1 (0.6–1.9)||.802|
|Mean poverty income ratio (family income/poverty threshold)||1.4 (0.7–2.9)||.3986|
|Low education (<high school graduation)||1.7 (1.1–2.7)c||.019|
|No health insurance||0.5 (0.1–2.3)||.404|
|Marital status (married or living with partner)||1.0 (0.5–1.7)||.9111|
|Current smoker (serum nicotine >10 ng/mL)||1.0 (0.5–2./2)||.993|
|Alcohol consumption (alcohol ≥1 time per mo)||0.8 (0.4–1.5)||.423|
|Illegal drug use (current or former use of marijuana, hashish, cocaine, and/or heroin)||0.3 (0.1–1.4)||.126|
|Mean sedentary leisure time (h per d of TV and computer use for entertainment)||1.1 (0.5–2.1)||.830|
|Unsatisfactory health (self-reported fair or poor health)||1.8 (1.1–2.8)c||.010|
|Overweight/obesity (body mass index ≥25 kg/m2)||1.7 (0.8–3.6)||.167|
|Central obesity (waist circumference >88 cm in women or >102 in men)||1.5 (0.9–2.7)||.131|
|Mean direct high-density lipoprotein, mg/dL||0.9 (0.6–1.4)||.635|
|Physician diagnosed diabetes||12.8 (7.4–21.9)c||<.0001|
|Poorly controlled diabetes (hemoglobin A1c≥7%)||3.1 (1.3–7.2)c||.008|
|Depression (PHQ-9 score≥10)||1.1 (0.7–1.7)||.786|
Table IV. Univariate ORs of Sleep Symptoms for Resistant Hypertensiona in Patients With Severe Hypertensionb
|Risk Factors||Unadjusted OR (95% CI)||P Value|
|Physician-diagnosed obstructive sleep apnea||1.0 (0.5–2.0)||.9687|
|Snoring (≥3 times per wk in the past 12 mo)||0.6 (0.3–1.0)||.0657|
|Snorting (≥3 times per wk in the past 12 mo)||0.6 (0.3–01.3)||.1905|
|Combined symptoms of sleep apnea (snoring or snorting ≥3 times per wk in the past 12 mo)||0.7 (0.5–1.1)||.0918|
|Severe symptoms of sleep apnea (snoring or snorting ≥5 times per wk in the past 12 mo)||0.9 (0.5–1.8)||.7744|
|Severe combined symptoms of sleep apnea (snoring and snorting ≥5 times per wk in the past 12 mo)||1.0 (0.3–3.0)||.9304|
|SHST <7 h per weeknight||0.9 (0.6–1.3)||.6045|
|SHST <6 h per weeknight||1.1 (0.5–2.5)||.8060|
|Mild/moderate insomnia (≥1 sleep disturbance 5–15 times mo and ≥1 daytime functional impairment)||1.2 (0.8–1.8)||.3249|
|Severe insomnia (≥1 sleep disturbance ≥15 times mo and ≥1 daytime functional impairment)||0.8 (0.3–1.9)||.6239|
|Insomnia with SHST <7 h per weeknight (≥1 sleep disturbance ≥5 times per mo and ≥1 daytime functional impairment and with SHST<7 h per weeknight)||1.0 (0.6–1.6)||.9565|
Multivariate analyses showed consistent association between poorly controlled diabetes and RHTN (OR, 3.0; 95% CI, 1.2–7.9) (Table V). Self-reporting fair or poor health was also a significant predictor of RHTN (OR, 1.7; 95% CI, 1.1–2.7). Snoring at least 3 times per week trended towards a reduced risk of RHTN (OR, 0.5; 95% CI, 0.3–1.1).
Table V. Multivariate ORs for Resistant Hypertensiona in Patients With Severe Hypertensionb
|Predictors in Final Model||Adjusted OR (95% CI)||P Value|
|Low education (< high school graduation)||1.5 (0.9–2.4)||.8122|
|Illegal drugs use (current or former use of marijuana, hashish, cocaine, and/or heroin)||0.3 (0.1–1.4)||.1093|
|Unsatisfactory health (self-reported fair or poor health)||1.7 (1.1–2.7)||.0289|
|Overweight/obesity (body mass index ≥25 kg/m2)||1.7 (0.8–3.8)||.1964|
|Poorly controlled diabetes (hemoglobin A1c≥7%)||3.0 (1.2–7.9)||.0245|
|Snoringc (≥3 times per night in the past 12 mo)||0.5 (0.3–1.1)||.0742|
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To the best of our knowledge, this is the first study that assessed the role of self-reported sleep complaints in severe hypertension as it exists in the community and distinguishing RHTN from medically matched patients with CSHTN. From this analysis, sleep symptoms did not predict RHTN, but other common health problems did. This analysis has the advantage of sampling from a nonclinic sample in a nationally representative US population cohort.
Poorly controlled diabetes and self-reported fair or poor health were significant, and probably more important, predictors for RHTN. The general association of diabetes and HTN is well-known. For instance, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), diabetes predicted lack of BP control during the course of the study.24 Conversely, clinical trials have indicated that in order to achieve the lower BP goal recommended for patients with diabetes, an average of 2.8 to 4.2 antihypertensive medications are required.25 The degree to which insulin resistance directly contributes to the development of HTN vs simply being associated with HTN because of common underlying causes (ie, obesity) remains to be determined. Pathophysiologic effects of insulin resistance per se may also contribute to HTN; these include increased sympathetic nervous activity, vascular smooth muscle cell proliferation, and increased sodium retention. Therefore, diabetic control could be proposed as an important health priority to help control RHTN. There has been a thought that patient’s overall level of well-being and perception of functional capacity may be more sensitive to the pharmacotherapy of antihypertensive drugs. Also, compliance, which is frequently related to a patient’s sense of deterioration in quality of life secondary to medical treatment, may well be the determinate of success with any antihypertensive regimen.26 One possibility is that the RHTN cohort, with greater unsatisfactory health, may not be as compliant to the pharmacologic therapy. While all of these factors can be indirectly attributed to poor sleep, chronic snoring, or untreated sleep apnea, self-reports of such conditions appear to take a backseat when RHTN is detected in the community.
It was contrary to our expectations that self-reported sleep symptoms did not relate to RHTN. In fact, there was a trend towards a protective effect of frequent snoring in terms of RHTN. Past studies including small hospital case series have shown that among cohorts with RHTN, OSA was highly prevalent.10 Our findings of a lack of association among RHTN, sleep symptoms, and sleep apnea could have resulted from a relative insensitivity or nonspecificity of these symptoms to detect OSA, whereas past studies used the “gold standard” polysomnography to diagnose OSA using values of apnea-hypopnea index. The use of polysomnography is cost prohibitive and thus was not done in the NHANES study. Further mechanistic and interventional studies are needed to address the role of sleep apnea in RHTN to understand what features of clinical studies have led to the belief that OSA is a risk factor of RHTN.3,27,28
While many studies have shown a significantly higher prevalence of HTN in habitual snorers than among nonsnorers,12,29 other studies have reported no association after the adjustment of confounding factors such as smoking, alcohol usage, age, and obesity.30,31 These observations are based on clinic cohorts where attributes of the presenting population in both medical and social domains could differ and offer different associations. The cause of the marginally significant protective role of snoring is unknown but could result from artifact secondary to screening and treatment decisions of OSA in RHTN vs CSHTN.
Strengths and Limitations
The strengths of the study include the national community-based sample of hypertensive patients. Limitations of the NHANES data include a cross-sectional design, self-reported data on sleep, and data paucity in respect to OSA treatment for patients already diagnosed with OSA in the cohort. The prevalence of severe HTN was found to be lower compared with previous published clinical studies. Since NHANES does not include recently hospitalized or institutionalized adults, some of the members of the population might be excluded from NHANES.