This study adds important information to the existing literature on aTRH. First, among participants taking antihypertensive medications from three or more classes, the prevalence of unhealthy lifestyle factors, particularly obesity, physical inactivity, low DASH diet score and high Na/K intake was high regardless of whether or not participants had aTRH. Second, none of the lifestyle factors was significantly associated with aTRH. There was a significant association between obesity and aTRH in an analysis that defined uncontrolled hypertension using lower cutpoints for participants with diabetes or chronic kidney disease. However, the magnitude of this association was small. Third, the clustering of unhealthy lifestyle factors was common in both aTRH and in those whose blood pressure was controlled on three antihypertensive medications; and the clustering of unhealthy lifestyle factors was not associated with aTRH.
Unhealthy lifestyle factors such as obesity, physical inactivity, smoking, heavy alcohol use, and a high salt diet have been identified as factors underlying difficult-to-control blood pressure [6
]. Obesity is associated with hypertension, higher blood pressure levels and a greater use of multiple antihypertensive medications [1
]. Similar associations have been reported for physical inactivity, smoking, heavy alcohol use, and a high salt diet.[28
] Thus, our finding that unhealthy lifestyle factors are common among participants taking antihypertensive medications from three or more classes is consistent with this prior literature.
It is unknown why unhealthy lifestyle factors was not associated with aTRH in our study. One explanation is that the prevalence of unhealthy lifestyle factors was also relatively high in participants whose blood pressure was controlled with antihypertensive medications from three classes, making it difficult to ascertain differences in unhealthy lifestyle factors between these participants and those with aTRH. For example, in our study, the prevalence of obesity was high not only in participants with aTRH but also in participants whose blood pressure was controlled on three antihypertensive medication classes. Similarly, in NHANES [2
], among participants on 3 or more antihypertensive medication classes, BMI was only modestly higher in participants with uncontrolled hypertension compared to participants with controlled hypertension in 2005–2008 (mean BMI was 32.3 kg/m2
and 31.8 kg/m2
respectively). Although obesity was higher among patients with aTRH compared to patients who had controlled hypertension while taking antihypertensive medications from 3 classes or less in a recent analysis of the Spanish Ambulatory Blood Pressure Monitoring Registry which included hypertensive clinic patients [29
], the difference in BMI between the two groups was modest (mean BMI was 30.8 kg/m2
and 29.3 kg/m2
Another explanation why unhealthy lifestyle factors did not have strong associations with aTRH is the relative contributions of other determinants of aTRH. We observed substantial differences in race, sex, and prevalence of comorbidities, particularly measures of chronic kidney disease and diabetes, between participants with aTRH and those with controlled hypertension. These factors may have played an important role in the development of aTRH, thereby diminishing the association between unhealthy lifestyle factors and aTRH. Unhealthy lifestyle factors could also have contributed indirectly to aTRH through the development of these comorbidities.
JNC 7 [15
] recommends that hypertensive patients undertake lifestyle modifications such as weight reduction, increasing physical activity, moderation of alcohol consumption, adoption of the DASH diet, dietary salt reduction, and the cessation of smoking. Most of these interventions have been demonstrated to lower blood pressure in unselected patients with hypertension or in those with mild to moderate hypertension [7
]. In contrast, the efficacy of lifestyle modification interventions for the treatment of aTRH has been largely untested [7
]. Pimenta et al. [30
] showed in a small crossover study of 12 participants with aTRH that a low salt diet reduced systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Therefore, salt restriction may improve blood pressure control for aTRH participants. Future randomized controlled trials should examine whether individual or multi-faceted lifestyle interventions can facilitate blood pressure control for patients with aTRH, particularly those with comorbidities such as chronic kidney disease and diabetes.
This study has a number of important strengths. The REGARDS study is one of the largest population-based cohort studies conducted in the United States. Black and white study participants were recruited from across the continental United States, and therefore, the findings are likely highly generalizable. Blood pressure was measured by trained technicians following a standardized protocol and medications being taken were recorded through direct inspection. Finally, since available data on the contribution of unhealthy lifestyle factors to aTRH are very limited, the current study provides new data on the etiology and pathogenesis of difficult-to-control blood pressure.
The current study also has several limitations. Many participants with aTRH may have been on suboptimal medication doses [8
]. However, medication dosing is not available in the REGARDS study database. In addition, blood pressure levels and control were defined by readings on a single visit. Ambulatory blood pressure monitoring was also not performed. Therefore, it is unknown how many participants had white coat and masked resistant hypertension. Finally, dietary measures (DASH diet and Na/K ratio) were obtained by the FFQ, and a limitation of dietary assessment instruments is measurement error.
In conclusion, in a bi-racial, population-based sample, unhealthy lifestyle factors did not demonstrate a strong association with aTRH among participants taking antihypertensive medications from three or more classes. The prevalence of unhealthy lifestyle factors, particularly obesity, physical inactivity, low DASH diet score and high Na/K intake were high regardless of whether participants had aTRH or not. Given the increasing prevalence of aTRH among US adults, studies are needed to assess whether lifestyle modification interventions are effective in facilitating blood pressure control in patients with aTRH.