Masked hypertension unfavourably affects haemostasis parameters

Blood Pressure, 2011; Early Online, 1–4 ORIGINAL ARTICLE
Masked hypertension unfavourably affects haemostasis parameters
D. P. PAPADOPOULOS 1 , C. THOMOPOULOS 2 , I. MOUROUZIS 1 , A. KOTROTSOU 1 , E. SANIDAS 1 , U. PAPAZACHOU 2 , M. DASKALAKI 2 & T.K. MAKRIS 2 1 ESH Excellent Center of Hypertension, Laiko Univesity Hospital, Athens, Greece, 2 ESH Excellent Center of Hypertension, Elena Venizelou Maternity Hospital, Athens Greece Abstract
Objective. Recent evidence demonstrates that masked hypertension (MH) is a signifi cant predictor of cardiovascular disease.
The aim of our study was to examine the impact of MH on haemostasis parameters and to compare the fi ndings to those
of healthy normotensives matched for age, sex, body mass index and the rest of risk factors.
(60 male, 70 female) healthy subjects mean age 45 Ϯ 12 years who had clinic blood pressure Ͻ 140/90 mmHg were studied. The whole study population underwent 24-h ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (eight males, 16 females) had MH (daytime systolic blood pressure Ն 135 mmHg or daytime diastolic blood pressure Ն 85 mmHg – group A) and the remaining 106 subjects (52 males, 54 females) had normal ABPM recordings – group B. Fibrinogen, thrombomodulin ™, the antigens of plasminogen activator inhibitor 1 (PAI-1Ag) and tissue plasminogen activator (tPA-Ag) were determined in the two groups. Results. The PAI-1 Ag, tPA-Ag, fi brinogen and TM levels were signifi cantly higher in the masked hypertensive group than to normotensive control group. Conclusions. Our fi ndings suggest that subjects with MH have signifi cantly higher fi brinogen, TM, PAI-1Ag and tPA-Ag plasma levels compared with normotensives. This observation may have prognostic signifi cance for future cardiovascular events in subjects with MH and needs further investigation. Key Words: Fibrinogen , hypertension , masked hypertension , plasminogen activator inhibitor 1 , thrombomodulin , tissue plasminogen
Introduction
longitudinal studies, MH was a strong predictor of cardiovascular outcome (11), mortality (12) and The phenomenon of masked hypertension (MH) defi ned as a clinical condition when patient offi ce It has been previously shown that essential blood pressure (BP) is less than 140/90 mmHg but his/her ambulatory or home BP readings are in the hypertension is associated with abnormalities in hypertensive range (1,2). Different BP thresholds Blood Press Downloaded from informahealthcare.com by Univ Rovira I Virgili on 03/14/11 have been proposed to defi ne MH, making it diffi - function, indicated by alterations in plasma levels of cult to compare results from various studies. Indeed fi brinogen, plasminogen activator inhibitor (PAI), the prevalence of MH in the general population tissue plasminogen activator (tPA) and thrombo- could be as high as 10%, whereas data obtained in modulin™ (15–18). Recent evidence is accumulating several cross-sectional studies have demonstrated that many of these markers are predictors of future large differences with prevalence rates from a low vascular events, both ischaemic heart disease and of 8% to a high of 49% (3–6). A body of evidence stroke (19,20). Only few previous studies have indicates that MH is a signifi cant predictor of cardio- examined a potential association between MH and vascular disease. Data obtained from several cross- these parameters (21). The aim of our study was to sectional studies reported that MH is associated investigate whether MH affects plasma levels of with increased left ventricular mass index (7–9) and haemostatic/fi brinolytic and endothelial function carotid intima-media thickness (10). Furthermore, in markers, including plasminogen activator inhibitor-1 Correspondence: Dimitris P. Papadopoulos, ESH Excellent Center of Hypertension, Laiko Univesity Hospital, Athens, Greece. Tel: ϩ 30-210-6563923. Fax: ϩ 30-210-6563923. E-mail: [email protected] (Received 14 November 2010 ; accepted 16 February 2011 ) ISSN 0803-7051 print/ISSN 1651-1999 online 2011 Scandinavian Foundation for Cardiovascular ResearchDOI: 10.3109/08037051.2011.565551 (PAI-1), tissue plasminogen activator antigen by the hospital review committee. At the baseline examination, all participants underwent a physical examination with a medical history, laboratory assessment of risk factors for cardiovascular disease and routine electrocardiogram. Subjects were weighed (kg), and height (m) was measured wear- This is a consecutively recruited cohort. A total of ing only light clothing without their shoes. The 285 patients that attended the Hypertension Clinic body mass index (BMI) was calculated as weight/ of our hospital were screened. All patients included in the study had clinic BP Ͻ 140/90 mmHg and were taking no anti-hypertensive medication or other medication that interferes with parameters measured Measurement of BP and laboratory assessment (e.g. aspirin, clopidogrel etc.) and were non-smokers. SBP and DBP were measured at the time of the fi rst All subjects were under standardized diet before and fi fth Korotkoff sounds, respectively. Measure- sampling and none of them had any thyroid func- ments were made on the right arm to the nearest tional abnormality; 145 out of 285 patients met these millimetre of mercury (mmHg) with the use of a mer- criteria. Five patients out of 145 that were initially cury sphygmomanometer. All measurements were enrolled were excluded from the study because of made in the supine position after the patient had inadequate ABPM recordings. Ten more subjects rested for 15 min. Results are the average of measure- from the normotensive group were excluded because ments obtained on at least three separate occasions, of inadequate blood samples. Finally, this study was which were performed by the same trained nurse, included in 130 (60 males, 70 females) subjects, who was not aware of the history of the subjects . The recruitment of MH subjects was made The whole study population underwent 24-h according to a document of the European Society ambulatory BP monitoring (ABPM). According to of Hypertension Working Group on Blood Pressure the ABPM recordings, 24 individuals had MH {19%} monitoring that defi ne individuals with MH those (daytime systolic BP, SBP Ն 135 mmHg or daytime who have clinic BP Ͻ 140/90 mmHg and daytime diastolic BP, DBP Ն 85 mmHg – group A) and the SBP Ͼ 135 mmHg or daytime DBP Ͼ 85 mmHg. remaining 106 subjects had normal ABPM record- This document was confi rmed from the 2007 pub- ings – group B. The demographic characteristics of lished edition of the European Society of Hyperten- the participants as well as the variables included sion guidelines (25). BP measurements consisted of in the recent guidelines of the European Society of clinic BP (see above), home BP (average of morning Hypertension to assess global cardiovascular risk and evening measurements, semiautomatic device), and ABPM with Spacelabs 90207, which recorded Alcohol consumption was determined by a BP every 20 min during daytime (between 10:00 questionnaire, which asked for the daily consump- and 20:00 h) and 40 min during night-time (between tion of wine, liquor and beer; alcohol intake was midnight and 06:00 h) for 24 h (3). Subjects expressed in grams per day. Information concern- recorded a daily action profi le from which informa- ing physical activity was obtained from question- tion about the precise times of sleeping and waking naires that have been previously described (23,24). were obtained. The onset of sleep was identifi ed as Before the study, written informed consent was Blood Press Downloaded from informahealthcare.com by Univ Rovira I Virgili on 03/14/11 the time that the subject went to bed. The subjects obtained from each participant, which was approved were instructed to carry out normal daily activities during the monitoring period. Table I. Demographic characteristics and standard laboratory Venous blood samples were collected without sta- sis after a 10-min supine rest. Participants were instructed to avoid strenuous physical activity and not to smoke tobacco during the hour preceding this examination, which took place between 08:00 and 09:00 h. All subjects had fasted for at least 12 h. Blood sampling was performed to determine plasma levels PAI-1-Ag, tPA-Ag and TM with an enzyme linked immunosorbent assay (ELISA; Diagnostica Stago, Asnieres, France). Fibrinogen levels were measured with Claus technique. Serum cholesterol and triglyceride levels were determined by an enzy-matic method and low-density lipoprotein (LDL) Group A includes patients with masked hypertension and group was calculated according to the Friedwald formula, B normotensive controls. SBP, systolic blood pressure; BMI, body since no subject had a triglyceride level higher than mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; DBP, diastolic blood pressure. Haemostasis parameters in masked hypertension our study group was found 19%, which is in the range reported in the general population. Values are expressed as the mean Ϯ SD. Differences Our results have shown increased levels of fi brin- between groups were analysed with t -test or Mann – ogen in masked hypertensive compared with normo- tensives. Fibrinogen is a major determinant of blood viscosity and it is also involved in haemostasis/throm-bosis pathways. Fibrinogen levels have been shown to be an independent predictor of subsequent car- diovascular events (19,20), underlining the clinical Clinic and ambulatory BP values are presented in Table I. Haemostatic/fi brinolytic parameters were The impact of MH on TM plasma levels was determined in 26 patients with confi rmed MH and also put under examination. TM is a protein cofac- 104 healthy normotensives. The two groups were not tor expressed on endothelial cells of most blood different with respect to age, gender, BMI, smoking vessels. Thrombin-bound TM activates protein C, status and lipid profi le (Table I). No differences were which inhibits thrombin generation by degrading observed between groups regarding physical activity, factors Va and VIIIa. TM has also been proposed as alcohol consumption and menopausal status (data a marker of endothelial cell damage and alterations in TM plasma levels have been found to be associ- The haemostasis balance parameters for each ated with EH and atherosclerosis (28,29). We found group are shown in Table II. The PAI-1 Ag, tPA-Ag, that TM levels are greater in masked hypertensive fi brinogen and TM levels were signifi cantly higher in than in normotensive group. These results are in the masked hypertensive group than in to normoten- agreement with the results of a previous study from our clinic showing that subjects with white coat hypertension have increased plasma levels of TM compared with controls. Although the precise Discussion
mechanisms of TM regulation are not yet quite clear, it has been suggested that hypertensive medi- The results of our study have shown that MH is asso- ated damage consequently results in endothelial ciated with increased plasma levels of PAI, tPA, fi brinogen and TM compared with subjects with nor- It has been previously shown that essential mal BP, indicating a decreased fi brinolytic capacity hypertension is often associated with decreased and endothelial damage. This fi nding indicates that fi brinolytic potential, procoagulant tendency and in our study population, MH is associated with a endothelial cell damage (15–18), the responsible state of decreased fi brinolytic capacity, which may pathways to this association remain controversial. potentially contribute to an increased incidence of This has been occasionally attributed to endothelial damage induced by increased BP or to several fea- The phenomenon of MH is defi ned as a clinical tures of the metabolic syndrome (30,31). It must also be noted that these abnormalities have been Ͻ 140/90 mmHg but ambulatory or home BP read- observed in normotensive offspring of hypertensive ings are in the hypertensive range (26) . The preva- or in hypertensive-prone subjects, indicating the lence of MH in the general population could be as Blood Press Downloaded from informahealthcare.com by Univ Rovira I Virgili on 03/14/11 contribution of other factors, unrelated to BP values, high as 10% (5), whereas data obtained in several including metabolic, neurohumoral and genetic cross-sectional studies have demonstrated large factors as well (32–34). Finally outcome studies have differences, with prevalence rates from a low of 8% suggested that MH increases cardiovascular risk, to a high of 49% (6,27). The prevalence of MH in which appears to be close to that of in-offi ce and out-of-offi ce (26). These data may provide a plau- Table II. Results and comparison between groups. sible explanation for the haemostatic abnormalities observed in masked hypertensives compared with normotensives, although offi ce BP remains in normal values. In conclusion, our study showed that masked hypertensive patients have increased plasma levels of PAI, tPA, fi brinogen and TM compared with normotensives, indicating a procoagulant tendency Group A includes patients with masked hypertension and group B Declaration of interest: The authors report no
normotensive controls. F, fi brinogen; TM, thrombomodulin; confl icts of interest. The authors alone are responsible PAI-1Ag, plasminogen activator inhibitor-1; tPA-Ag, tissue plasminogen activator . for the content and writing of the paper. References
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