Relationship between Socioeconomic Level, and the Prevalence of Masked Hypertension and Asymptomatic Organ Damage

Background

The term masked hypertension (MHT) was first used by Pickering in 1992 [1,2]. MHT occurs when the mean 24-h ambulatory blood pressure measurement (ABPM) ≥130/80 mm Hg or mean non-clinical (home or a pharmacy) periodic blood pressure measurement is ≥135/85 mm Hg despite normal (<140/90 mm Hg) polyclinic blood pressure [3]. The prevalence of MHT was observed to be 10–17% in general population-based studies [3]. MHT can lead to severe target organ damage if not diagnosed or treated in a timely fashion. A few recent studies have suggested that although MHT patients appear to be normotensive upon presentation to polyclinics, they are similar to patients with sustained hypertension (SHT) [4–6] in terms of asymptomatic organ damage (AOD) [left ventricular mass index (LVMI) >95 g/m2 for females and >115 g m2 for males, carotid intima media thickness (CIMT) >0.9 mm, microalbuminuria (urinary albumin [U-Alb] level 30–300 mg/dl, and grade 3 or 4 retinopathy] [3]. Another study on hypertensive patients receiving treatment reported that AOD was more common in the MHT group than in the SHT group [7].

Because MHT often remains undetected and is difficult to diagnose – even when patients are examined by a doctor – the prevalence of both MHT and AOD may be high among individuals of low socioeconomic status. To the best of our knowledge, the literature does not include any studies on MHT-associated AOD in a low socioeconomic population. As such, the present study aimed to determine the prevalence of MHT and its association with AOD in a low socioeconomic district of Ankara, Turkey.

Material and Methods

AMBULATORY BLOOD PRESSURE MONITORING:

The WatchBP 03 device (Microlife WatchBP AG, Switzerland) was used for 24-h ABPM. Patients were provided information about how to use the device. They were instructed to perform their normal daily activities, but to remain motionless during measurement recording. The devices were programmed to take SBP and DBP measurements for 24 h as follows: every 15 min between 07:00 and 23:00 (daytime) and every 20 min between 23:00 and 07:00 (night time). The method was considered reliable if >70% of measurements were valid.

ECHOCARDIOGRAPHIC EXAMINATION:

Echocardiography was performed by an technician blinded to the patients’ clinical data, using a commercially available echocardiography machine (Vivid 7, GE-Vingmed Ultrasound AS, Horten, Norway) equipped with a 2.5-MHz phased array transducer. Complete 2D, color, pulsed, and continuous-wave Doppler examinations were performed, according to standard techniques. Left ventricular mass (LVM) was calculated from 2D echocardiographic measurements using the Devereux formula:

The obtained LVM values were indexed to body surface area and are presented as the LVM index (LVMI) [11].

CAROTID INTIMA-MEDIA THICKNESS MEASUREMENT:

Carotid intima-media thickness was measured by a radiologist blinded to the patients’ clinical status while the patients were in the supine position with their hand bent backwards, using a high-resolution B-mode ultrasound device (Logic 7, GE Med. Inc., USA), a linear probe on the right and left common carotid artery, and an automated system. Measurements were performed at 3 different points: the right and left common carotid artery, bifurcation, and the first 2 cm of the internal carotid artery. Longitudinal measurements were obtained from the distances defined as vessel lumen echogenicity and media-adventitia echogenicity [12]. Mean CIMT was calculated based on the average of 3 measurements from each carotid artery [13].

FUNDUSCOPIC EXAMINATION:

For funduscopic examination, 1 drop of tropicamide 1% solution was dripped into each eye 15 min prior to examination using a biomicroscopy device (Topcon SL-3C, Topcon Corp., Japan). Retinopathy staging was in accordance with 2013 European Society of Hypertension and European Society of Cardiology Hypertension guidelines, as follows: Grade I: arteriolar narrowing – either focal or general in nature; grade II: arteriovenous nicking; grade III: retinal hemorrhages, microaneurysms, hard exudates, and cotton wool spots; grade IV: grade III signs plus papilledema and/or macular edema [3].

BIOCHEMICAL PARAMETERS:

The patients were provided written and verbal instructions on how to collect and store 24-h urine samples. The turbidimetric method was used to measure 24-h urinary protein and microalbumin; albumin was measured using the bromocresol green method; fasting blood sugar, creatinine, uric acid, total protein, total cholesterol, and triglyceride were measured via the colorimetric enzymatic method; and high-density lipoprotein (HDL) cholesterol was measured via the homogenous colorimetric enzymatic method using an Hitachi Modular P800 (Roche Diagnostics Corp. Indiana, USA) analyzer. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald method. The glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation:

STATISTICAL ANALYSIS:

All statistical analyses were performed using SPSS v.20.0 for Windows (IBM Corp., Armonk, NY). The Kolmogorov-Smirnov test was used for data with normal distribution. Numeric parameters with normal distribution are shown as mean ±SD, and those not normally distributed are shown as median (range). Categorical variables are expressed as number and percentage. Correlations between numeric parameters were analyzed using Pearson’s and Spearman’s correlation analyses. Categorical variables were compared via the chi-square test and Fisher’s exact chi-square test. Differences between groups in numeric parameters with normal distribution were analyzed using the t test for independent samples, and differences between groups in numeric parameters not normally distributed were analyzed using the Mann-Whitney U test. Stepwise multivariate robust regression analysis was used to identify factors that increase the risk of target AOD. The level of statistical significance was set at P<0.05.

Results

The data set included records for 712 patients (288 males and 424 females) with a mean age of 57.1±9.6 years. In all, 206 (28.9%) patients were considered hypertensive based on blood pressure >140/90 mmHg; among the remaining 506 patients (164 males and 342 females) with a mean age of 57.1±9.6 years, 73 (10.2%) were diagnosed as MHT based on mean polyclinic measured SBP <140 mmHg and DBP <90 mmHg, and mean home-measured SBP >135 mmHg and DBP >85 mmHg. In total, 433 (60.8%) patients were considered normotensive based on mean polyclinic-measured blood pressure <140/90 mmHg and mean home-measured blood pressure <135/85 mmHg.

Of the 73 patients diagnosed with MHT, 30 were not examined for AOD (Figure 1). Demographic characteristics of the remaining 43 (23 males and 20 females, mean age of 52.6±9.4 years) MHT patients and the EHT group (86 patients, 46 males and 40 females, mean age of 49.9±10.7 years), and the indicators for AOD are presented in Table 1. The MHT and EHT groups were similar in terms of age, sex, BMI, and mean 24-h blood pressure, whereas the duration of hypertension was significantly longer in the EHT group than in the MHT group (3.3±0.9 years vs. 2.0±0.6 years, P<0.001). The AOD indicators CIMT (0.91±0.2 mm vs. 0.70±0.1 mm) and LVMI (95.7±18.2 g/m2vs. 84.6±20.9 g/m2), and the mean microalbuminuria level (22 mg/d vs. 10.25 mg/d) and retinopathy stage were significantly higher (P<0.05) in the MHT group than in the EHT (Figure 2).

There was a positive correlation between the mean 24-h SBP and LVMI level in the MHT and EHT groups. Mean 24-h SBP was positively correlated with CIMT and the microalbuminuria level in the EHT group but there was no correlation in the MHT group. There was a positive correlation between retinopathy stage and mean 24-h SBP in the MHT group, but there was no correlation in the EHT group. There was no significant relationship between mean 24-h DBP and LVMI in the MHT group or EHT group. In the EHT group, mean 24-h DBP was positively correlated with CIMT and the microalbuminuria level, but in the MHT group there was a positive correlation only between 24-h DBP and the microalbuminuria level. Retinopathy stage was positively correlated with mean 24-h DBP in the MHT group, but not in the EHT group (Table 2).

In the EHT group, LVMI was positively correlated with age and mean 24-h SBP, and was negatively correlated with the creatinine level, but was not significantly correlated with any of the other parameters. In the MHT group, only LVMI was positively correlated with mean 24-h SBP. In the EHT group, CIMT was positively correlated with age, mean 24-h SBP, and mean 24-h DBP, and was negatively correlated with the albumin level, but was not significantly correlated with the other parameters. In the MHT group, age was positively correlated with the fasting blood sugar level and was negatively correlated with GFR, total cholesterol, and LDL levels. In the EHT group, the microalbuminuria level was positively correlated with mean 24-h SBP and the uric acid level, but was not significantly correlated with the other parameters. In the MHT group, there was a positive correlation between the microalbuminuria level and mean 24-h DBP (Table 3).

Based on a stepwise regression model used for analyzing risk factors (age, sex, BMI, duration of hypertension, current smoking, habitual drinking, 24-h SBP, 24-h DBP, MHT, fasting blood sugar, GFR, total protein, albumin, uric acid, cholesterol, triglyceride, LDL, and HDL), we found that age, MHT, and mean 24-h SBP were predictors of LVMI. Age, MHT, mean 24-h SBP, fasting blood sugar level, and albumin level were observed to be predictors of CIMT. MHT, mean 24-h SBP, and uric acid level were predictors of microalbuminuria level (Table 4).

Discussion

The prevalence of MHT in the present study was 10.2%. Mean LVMI, CIMT, 24-h urinary microalbuminuria level, and retinopathy stage were significantly higher in the MHT group than those in the EHT group. To the best of our knowledge, the present study is the first to examine the relationship between MHT and AOD in Turkey. Although the prevalence of MHT in the present study is similar to that reported by other studies [5,15,16], we think that the prevalence was higher as compared to other districts of Ankara because this review was performed in a district where socioeconomic status was low, the workload was heavy, and the working stress was high.

Regarding subgroups of hypertensive patients and AOD, Liu et al. performed a cross-sectional study that included 359 patents with hypertension and reported that LVMI and CIMT were similar in the SHT and MHT patients, but higher than in normotensive patients [4]. Similarly, the Pressione Arteriose Monitorate E Loro Associazioni (PAMELA) study, which included 3200 hypertensive patients, reported that LVMI and CIMT were similar in the MHT and SHT groups [5]. Other studies reported that the prevalence of AOD in MHT patients is similar to that in SHT patients, but higher than that in controlled hypertension and white coat hypertension groups [17–20]. In contrast, a study performed that included 332 patients with hypertension reported that CIMT, LVMI, and urinary albumin were higher in the MHT group than in the SHT, white coat hypertension, and controlled hypertension groups [7]; however, to the best of our knowledge, the literature is devoid of any study on the relationship between normotensive MHT and EHT patients receiving therapy, and AOD.

Although the duration of hypertension was significantly shorter in the present study’s normotensive MHT group receiving treatment than in the EHT group, the levels of AOD indicators were higher in the MHT group, which could be interpreted in several ways. Firstly, most of the patients in the MHT group were engaged in strenuous manual labor and the resultant high level of oxidative stress might have triggered inflammation leading to target organ damage [21]. Secondly, it could be that the patients in the MHT group were diagnosed late due to either hypertension patterns or their social status, and as a result had high blood pressure for a long time. Lastly, it is possible that the MHT group included more patients with morning hypertension or nighttime hypertension, which are often associated with more negative effects of target organ damage [22] than the EHT group.

In 2 large-scale prospective studies, Clement (22) and Bobrie (23) reported that even though office-based blood pressure in patients treated for hypertension was kept under control, high ambulatory or home systolic blood pressure was suggested to be a strong predictor of cardiovascular morbidity. Another study that included subgroups of hypertensive patients, daytime SBP and MHT were reported to be independent indicators of LVMI, CIMT, and microalbuminuria [7]. Similarly, in the present study, MHT and 24-h SBP were observed to be predictors of such indicators of AOD as LVMI, CIMT, and microalbuminuria in all of the patients treated for hypertension.

The present study has several limitations. Accurate identification of AOD might have been hampered by the study’s retrospective design and small study population; as such, we think prospective research with larger study populations is needed to more effectively assess the effect of MHT on target organ damage. Another limitation of the present study is that the patients did not all use the same antihypertensive medication. Because the cardioprotective and renoprotective effects of the medications they did use varied, future studies should include patients using the same medication, or multivariate regression analysis should be employed to determine the effects of all medications used by hypertensive patients on MHT and AOD.

Conclusions

The present study determined that the prevalence of MHT in a low socioeconomic district of Ankara is similar to that reported by other population-based studies; however, AOD was significantly more common in the MHT group than in the EHT group. Based on these findings, we think that patients that present due to symptoms of hypertension that are normotensive at presentation should measure their blood pressure at home. In such MHT patients, AOD screening should be performed at the onset of treatment, followed by initiation of antihypertensive medication. Larger scale, longer term studies are needed to more clearly understand the effect of MHT on cardiovascular outcome.