This observational and cross-sectional study surveyed demographic findings, clinical characteristics, and antihypertensive medication classes in hypertensive patients at 230 primary care clinics in Korea. The purpose of our study was to evaluate the prevalence of the patients who corresponded to the criteria of RH, and to determine the demographic and clinical features that distinguish high-risk individuals who develop RH from all hypertensive patients.
In this study, the prevalence of RH was 7.9 % (N = 244), which is lower than the prevalence reported in some studies. This phenomenon may be explained by the different conditions of our study, as compared with other studies. In the Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) trial and the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the prevalence of RH was 18 and 15 %, respectively. Those data were examined from patients who were 55 years or older who had one or more additional cardiovascular risk factors [13, 14]. In another study, target blood pressure was defined as less than 130/80 mmHg if the patients had diabetes mellitus or kidney disease, which led to 9.1 % of patients defined as having RH [6]. In our study, however, patients were 18 years or older and did not require any cardiovascular risk factor for enrollment. We used the new Joint National Committee 8 guideline that define target blood pressure (<140/90 mmHg) to be the same for patients with and without diabetes mellitus and kidney disease [8]. Another hypothesis, which may help explain the lower prevalence of RH in our study, is that those patients with uncontrolled hypertension may have already been referred to the hospital for further evaluation and clinical management. According to the 2013 Report of Assessment for quality of hypertension treatment in Korea, about 30 % of hypertensive patients receive medications from hospitals, rather than primary clinics [15]. Thus, the prevalence of RH at primary clinics may be lower than that of RH at hospitals.
Moreover, the prevalence of RH may be overestimated at primary clinics. In the present study, the prevalence of uncontrolled hypertension was 31.4 %, much higher than that reported in other studies (13–17 %) [5]. Forced titration of antihypertensive medications by the physician may also contribute to the improved control rate of hypertension. If patients had uncontrolled RH and were taking three medications, including a diuretic, they would be reallocated from the RH group to the controlled non-RH group; thus, the prevalence of RH would be decreased.
We showed several predictors to be associated with RH: electrocardiographic LVH, renal impairment, current smoker, abdominal obesity, and cardiovascular disease. In particular, hypertensive patients with electrocardiographic LVH were 2.3 odds (1.39–3.80, 95 % confidence interval) more likely to have RH compared to those without electrocardiographic LVH. LVH is not only one of the most important subclinical cardiac alterations that result from continuous high blood pressure but also represents a target organ damage [16]. In addition to a chronic pressure overload, overexpression of humoral and hormonal factors are also attributed to the development of cardiac hypertrophy in patients with RH and obstructive sleep apnea, hyperaldosteronism, or both [17]. Although it has yet to be established whether LVH aggravates hypertension, if patients with uncontrolled hypertension have electrocardiographic LVH, further evaluation for the attributed causes of LVH may be needed to improve the clinical management of hypertension.
The prevalence of RH in the subgroup with renal impairment (N = 698) was 11.0 %, in our study. Previous studies have reported the prevalence of RH to be 50 % or more [18]. Chronic renal parenchymal disease has been ascertained as the most common identifiable secondary cause of RH. Possible mechanisms, by which decreased renal function leads to development of RH, include the retention of sodium and fluid and the up-regulation of the renin-angiotensin system [19, 20]. Thus, the use of diuretics and ACE inhibitors or ARBs should be considered in patients with increased serum creatinine or estimated GFR.
Lifestyle modifications, such as weight reduction and smoking cessation, may also help improve hypertension management. Although the exact mechanism by which obesity increases blood pressure is not well understood, excess weight gain has been reported as the best predictor for the development of hypertension [21]. Obesity can lead to increased renal sodium reabsorption and renal injury through the activation of the renin-angiotensin system and increased sympathetic tone [22].
Identifying individuals at high risk of developing RH, who have electrocardiographic LVH, renal impairment, abdominal obesity, current smoking, or cardiovascular disease, is important for the selection of appropriate antihypertensive medications. Difficulty in controlling blood pressure in patients with the aforementioned predictors should prompt earlier consideration of forced titration of medications and evaluation for secondary hypertension.
This study has some limitations. First, drug adherence was not measured accurately. Poor adherence to antihypertensive medications is a well-known, major cause of failure to reach target blood pressure [23]. However, pill count and patient education were performed at each visit to the clinic. Second, although we excluded patients with a history of secondary or white-coat hypertension from the initial recruiting, estimation of the prevalence of pure RH was not perfect. It was difficult to perform sophisticated examinations for all patients with uncontrolled hypertension in the primary care setting. The final objective of this study was to manage hypertension effectively by identifying patients who corresponded with the criteria of RH. If secondary or white-coat hypertension is in doubt, referral to a hospital or hypertension-specialized institution may be indicated. However, the results of our study are valuable because they represent the first investigation of RH at primary clinics in Korea, and are robust, in that they are derived from 3088 patients and 247 primary physicians.