Ambulatory blood pressure monitoring can unmask hypertension in patients with psoriasis vulgaris

Background

Psoriasis vulgaris is one of the most prevalent chronic, multisystemic, inflammatory skin disorders. It is characterized by formation of inflamed plaques in the skin, scalp, nails, and joints [1,2]. It affects nearly 3% of the global population, including 125 million people worldwide [3]. Although the pathogenesis of psoriasis is still not fully understood, increased oxidative stress, endothelial dysfunction, and systemic inflammatory response are considered as the most important mechanisms in the development of the disease, as is the case in most cardiovascular diseases [4]. Patients with psoriasis have excess risk of atherosclerotic vasculopathies such as coronary artery disease, hypertension, metabolic syndrome, obesity, and diabetes mellitus [5–7]. It has been clearly demonstrated that arterial hypertension is common in patients with psoriasis vulgaris, with a prevalence of 8.9% to 44.4% [8–10]. Although hypertension risk was found to be correlated with severity of psoriasis, hypertension was even more frequent in patients with mild disease compared to normal individuals when other variables like age, smoking, alcohol consumption, body mass index (BMI), and physical activity had taken into account [10].

Masked hypertension (MH) is a clinical entity defined in subjects who have normal office blood pressure (BP) (<140/90 mmHg) but elevated ambulatory or home BP (daytime systolic BP >135 mmHg or daytime diastolic BP >85 mmHg) [11]. It is closely associated with development of sustained hypertension, cardiovascular morbidity, and mortality [12–14]. The prevalence of MH in the general population was estimated at 8% but it increased to 49% in specific study groups [15–19]. Some of the factors leading to MH have defined as older age, male sex, smoking, contraceptive use in women, and sedentary lifestyle [20]. The percentage of masked hypertensives among patients with psoriasis is not clear. The adverse cardiovascular outcome of these patients could be related to a higher percentage of MH. The aim of the present study was to determine the prevalence of MH in subjects with psoriasis vulgaris as evaluated by 24-h ambulatory BP monitoring (ABPM) device. Additionally, clinical variables and laboratory findings associated with MH were investigated.

Material and Methods

STUDY DESIGN:

The study was carried out at the Dermatology and Cardiology clinics of Bezmiâlem Foundation University Hospital, Istanbul, Turkey. A cross-sectional study design was used to compare the prevalence of MH in patients 18–45 years old with psoriasis vulgaris and controls. The patient group consisted of eligible patients selected from consecutive patients with psoriasis vulgaris admitted to the outpatient clinic of the Dermatology Department (Group 1). Also, age-, sex-, and BMI-matched subjects with normal office BP from the Cardiology Department outpatient clinic were used as the control group (Group 2). Control subjects were selected from subjects who were admitted to the hospital for symptoms suggesting high BP such as headaches and dizziness with normal office BP. This study was approved by the Bezmiâlem Foundation University, School of Medicine Ethics Committee and was conducted in accordance with the ethics principles described by the Declaration of Helsinki. Written informed consent was obtained from all participants.

STUDY POPULATION:

Patients who had past or concurrent diseases such as essential hypertension (office BP ≥140/90 mmHg and/or average 24-h ambulatory BP ≥135/85 mmHg), diabetes mellitus, dyslipidemia (a total cholesterol level >240 mg/dl or taking lipid-lowering agents), obesity (BMI ≥30 kg/m²), coronary artery disease, liver or kidney diseases, collagen vascular diseases, any cardiovascular drug use, or abnormal thyroid function were excluded from the study. None of the patients had a history of a respiratory disease such as asthma, chronic obstructive pulmonary disease, emphysema, or chronic bronchitis. Also, participants with current or previous (within the last 6 months) use of oral contraceptives, hormone replacement therapy, glucocorticoids, non-steroidal anti-inflammatory drugs, methotrexate, hydroxyurea, mycophenolate mofetil, azathioprine, oral retinoids, ciclosporin, or adalimumab were excluded from the study. Participants who reported that their sleep was severely disturbed when wearing the ABPM device were also excluded.

A complete physical examination was performed on all subjects, including measurement of height, weight, heart rate, and BP. The BMI was calculated as weight in kg/height in square meters for all subjects. Waist circumference, taken midway between the lowest rib and the iliac crest, and hip circumference, taken at the level of the greater trochanters, were measured to the nearest millimeter using a flexible tape.

Blood samples were collected following a 12-h overnight fast and analyzed by the hospital clinical laboratory. Fasting blood samples were obtained for glucose, lipids, high sensitivity C-reactive protein (hs-CRP), creatinine, and white blood cell count (WBC). Biochemical and hematological parameters were measured by an Olympus AU 600 autoanalyzer (Olympus Optical Co., Ltd., Schimatsu-Mishima, Japan) and Bayer Advia 120 Cell CBC Counter Hematologia autoanalyzer (Bayer Advia 120 CBC counter, NJ, USA). Hs-CRP was measured by the high-sensitivity nephelometric method (Dade Behring, Marburg, Germany). Total cholesterol, triglycerides, and high-density lipoprotein cholesterol were analyzed enzymatically using a Hitachi 747 (Japan) analyzer. Low-density lipoprotein cholesterol was calculated using the Friedewald formula.

EVALUATION OF PATIENT DISEASE ACTIVITY:

The diagnosis of psoriasis vulgaris was based on dermatologist diagnosis and/or description of characteristic lesions. Disease duration ranged from 6 months to 35 years (mean range, 12.8±8.3). The clinical severity was determined according to the Psoriasis Area and Severity Index (PASI) [21]. The PASI assesses 4 body regions: the head, trunk, upper extremities, and lower extremities. For each region, the surface area involved is graded from 0 to 6 and each of 3 parameters (erythema, thickness, and scaling of the plaques) is graded from 0 to 4. The scores from the regions were summed to give a PASI score ranging from 0 to 72. The Psoriasis Severity Index (PSI) was also used to evaluate clinical signs (erythema, thickness, and scaling) on a scale of 0 (absent) to 3 (severe), for a possible total score up to 3 [22]. Affected body surface area (BSA) was also evaluated. The Nail Psoriasis Severity Index (NAPSI) was used to quantify the degree of nail changes [23]. The NAPSI was assessed separately for each fingernail and toenail. It is a numeric, simple tool for evaluation of nail psoriasis. This scale was used to evaluate the severity of nail bed psoriasis and nail matrix psoriasis. Each nail was evaluated for the presence or absence of nail matrix disease (pitting, leukonychia, red spots in lunula, nail plate crumbling) and nail bed disease (oil drop salmon patch discoloration, onycholysis, nail bed hyperkeratosis, and splinter hemorrhage). The sum of the scores for all of the nails was the patient’s NAPSI. Nail involvement was considered for patients with NAPSI score ≥1. Table 1 summarizes the disease-specific characteristics of the patients.

OFFICE BLOOD PRESSURE MEASUREMENT:

Office BP was measured from the brachial artery using a mercury sphygmomanometry (ERKA D-83646 Bad Tölz, Kallmeyer Medizintechnik GmbH & Co. KG, Germany). An appropriate cuff size was chosen for each subject. Systolic and diastolic BPs were taken as the first and fifth phases of Korotkoff sounds. The office BPs were measured by trained medical personnel at admission during the physical examination and then on the following day before ABPM. After at least 5 min of sitting rest, BP was measured 2 times with 1-minute intervals. The average of these measurements was used to determine office BP. The repeatability of BP measurements with a mercury sphygmomanometer was calculated by an intra-class correlation coefficient (0.92; 95% CI: 0.90–0.94; p=0.001). If the readings differed by 5 mmHg, an extra reading was obtained. The average of these 3 readings was defined as office BP. None of the readings were dropped. Extra measurements were required for only 5 subjects. Two sphygmomanometric office BPs were taken by trained medical personnel (during the physical examination and then on the following day before ABPM). The agreement analysis between devices was performed on the healthy subjects. The interclass correlation coefficient between a mercury sphygmomanometer and an ABPM device was calculated as 0.86 (95% CI: 0.82–0.90; p=0.001).

AMBULATORY BLOOD PRESSURE MONITORING:

Twenty-four-hour ABPM was carried out with a validated non-invasive automatic device (Tonoport V, PAR Medizintechnik GmbH, Berlin, Germany) and the cuff of the device was fitted on the non-dominant arm. Patients were instructed to maintain the same daily routine and sleep patterns and to stop muscular activity (especially sports activity) and to keep their arms entirely still during BP measurements. The BP monitor was programmed to measure BP at intervals of 20 min during the daytime and 30 min at night. Each BP reading was edited by a computer and rejected if the systolic BP was less than 80 mmHg or more than 250 mmHg or if the diastolic BP was less than 40 mmHg or more than 140 mmHg. Recordings for each subject were accepted if more than 80% of the raw data were valid. Average values were calculated for 2 periods of a whole day: a 5-h period between 1 AM and 6 AM (nighttime) and a 12-h period between 9 AM and 9 PM (daytime). Average daytime ABPM of less than 135/85 mmHg and average nighttime ABPM of less than 120/70 mmHg were considered as normotensive (Group 1) [11,24]. Patients with 24-h ambulatory BP above these limits but normal office BP were considered as masked hypertensive (Group 2) [25]. The percentage of decline in sleep BP was calculated as follows: decline in sleep SBP (%) = (daytime average SBP – nighttime average SBP) ×100/daytime average SBP. Non-dippers are defined as those who showed a reduction in BP of less than 10% between the average daytime and nighttime SBPs. If the nighttime SBP decrease was ≥10%, it was classified as dipper [24]. The average of BPs during the first 4 h after waking was defined as morning BP [26].

STATISTICAL ANALYSIS:

Statistical analysis was carried out using SPSS for Windows version 13.0 (SPSS, Chicago, IL). Categorical variables are presented as frequency and percent, and compared with the chi-squared test. Normally distributed continuous variables are presented as mean ± standard deviation, and compared with the independent samples t-test. Non-normally distributed continuous variables were presented as median and range, and compared with the Mann-Whitney U test. The distribution of the variables was determined with the Kolmogorov-Smirnov Z test for each study group. Those variables whose univariate associations trended toward statistically significance were considered for construction of the multivariate model. Stepwise backward logistic regression was performed to identify independent predictors of MH. A p value of <0.05 was considered statistically significant for all the tests.

Results

The main characteristics and laboratory findings of patients are summarized in Table 2. The study enrolled 110 psoriatic patients who had normal office BP (systolic 114.7±11.6, diastolic 72.7±8.0 mmHg) and 110 normotensive subjects (systolic 116.9±9.8, diastolic 73.5±8.7 mmHg). Both groups were similar in terms of age, sex, anthropometric measures such as BMI, waist, and hip circumference, and laboratory measures of lipid profile and fasting glucose.

All of the patients successfully (capturing ≥80% valid readings) completed 24-h ABPM (total 54 measurements, 12 of them during the night between 1 AM and 6 AM). The average ABPM session duration was 21.4 h. The average percentage of valid readings obtained was 87%. Fifty-four perfect readings were obtained in 79 patients (73.1% of the study population). An even worse number was 46/54 measurements (85% success). The nighttime and 24-h average BP values (SBP, DBP, and MABP) and daytime SBP were significantly higher in patients with psoriasis vulgaris compared to the control subjects (Table 3). The decline in BP during the night was blunted in psoriatic patients (for systolic BP, 9.2±4.7 vs. 8.4±3.8 mmHg, p=0.41) and patients with non-dipper BP profile were common in Group 1 (34/75, 45.3% in Group 1 and 21/33, 63.6% in Group 2, p=0.08). The average MABP values at early morning were also elevated in psoriatic patients (p<0.01).

The characteristics of participants with and without MH are shown in Table 4. The prevalence of MH was 24.1% (53/220). MH was more common in patients with psoriasis vulgaris compared to control subjects (35/110, 31.8% vs. 18/110, 16.4%, p<0.01) (Figure 1). Male sex, smoking, being overweight and having central obesity (higher BMI, waist and hip circumferences), and dyslipidemia (higher triglyceride and lower HDL cholesterol levels) were associated with MH (Table 4). These variables were entered into a binary logistic regression analysis for the detection of the predictors of MH, which revealed male sex and BMI as independent predictors of MH in the whole study population (Table 5).

Similar to the results of the whole study population, MH was associated with male sex (28/35 vs. 28/75, p<0.01), smoking (23/35 vs. 32/75, p=0.04), and obesity-related anthropometric measures such as BMI (27.5±2.6 vs. 25.8±3.1, p<0.01) and waist circumference (102.1±10.1 vs. 94.0±9.9 cm, p<0.01) in patients with psoriasis vulgaris. MH was significantly associated with severity of the disease. Disease-specific indexes (PASI, BSA, and PSI) were significantly higher in patients with MH (p<0.01). To define predictors of MH in patients with psoriasis vulgaris, clinical characteristics and disease-specific indexes found to be significantly associated with MH were entered into the binary logistic regression with backward stepwise methods (sex, smoking, BMI, waist circumference, PASI, BSA, and PSI). Male sex, waist circumference, and BSA were found to be the independent predictors of MH in patients with psoriasis (Table 6).

Discussion

STUDY LIMITATIONS:

The small number of subjects was the most important limitation of this study. The other limitation was absence of BP follow-up in both groups. Alcohol consumption and the frequency of leisure physical activity of the subjects were not measured. Also, we did not evaluate patients for target organ damages such as left ventricular hypertrophy, microalbuminuria, renal dysfunction, and carotid artery wall thickness. The ABPM was taken at several different postures including supine position during sleep and standing posture during daily physical activity, which could affect the accuracy of BP measurement. Moreover, we do not have data before and after initiation of therapy to see whether this treatment affects circadian BP pattern. For this reasons, large-scale and long-term follow-up prospective studies are required to establish the predictive value of MH for adverse cardiovascular events in patients with psoriasis vulgaris.

Conclusions

In conclusion, our study revealed that MH is highly prevalent in normotensive patients with psoriasis vulgaris, even if they are young and non-obese. It may be speculated that increased incidence of MH in psoriatic patients could predispose to target organ damage and adverse cardiovascular outcomes. Further prospective studies are warranted not only to verify this relationship but also to elucidate the exact mechanisms. These findings confirm that psoriatic patients, even those who were normotensive and with mild disease, had increased cardiovascular risk. Physicians caring for patients with psoriasis vulgaris should not only treat skin lesions but also screen them for different types of hypertension such as MH. Use of an ABPM device could represent the hidden part of the iceberg and it should be ordered as a part of suggested screening for hypertension. These patients should be monitored more closely and be evaluated for end-organ damage such as microalbuminuria, left ventricular hypertrophy, and carotid artery thickness. Lifestyle modification including low-salt diet, weight reduction, exercise, and smoking cessation should be recommended, and medical treatment should be ordered immediately if necessary. It should be noted that younger patients profit most when preventive strategies are implemented early.