Abstract
Arterial damage of large arteries, addressed as c‐f PWV, is recognized as independent predictor for future cardiovascular disease. The aim of this study was to systematically investigate the association of the four hypertension phenotypes with carotid‐femoral pulse wave velocity (c‐f PWV), in untreated patients. PubMed and Cochrane Library were searched to identify studies comparing c‐f PWV levels between normotensives, sustained hypertensives, white‐coat hypertensives (WCH), and masked hypertensives (MH). Meta‐analysis was performed to compare the difference c‐f PWV levels between these groups. Newcastle‐Ottawa quality assessment scale for cross‐sectional studies was used to assess study quality. MH and WCH patients had significantly increased c‐f PWV values compared to the normotensive groups (d = 0.96 m/s, 95% CI: 0.49‐1.42; I2 = 85%, P < .01 for MH and d = 0.85 m/s, 95% CI: 0.48‐1.22; I2 = 89%, for WCH). Moreover, the sustained hypertensive population was found to have significantly increased values of c‐f PWV compared to MH (d = −0.70 m/s, 95% CI: −0.87 to −0.54; I2 = 12%, P = .33) but not compared to WCH population (d = −0.75 m/s, 95% CI: −1.52‐0.02; I 2 = 96%,). Finally, there was no significant difference between MH and WCH population (d = 0.06 m/s, 95% CI: −1.04 to 1.15; I 2 = 96%,). MH and WCH population may have increased values of c‐f PWV compared to the normotensive group. These results demonstrate that these phenotypes are not clinically innocent, in the untreated population.
Keywords: arterial stiffness, masked hypertension, meta‐analysis, pulse wave velocity, systematic review, white‐coat hypertension
1. INTRODUCTION
Nowadays, hypertension still remains one of the main causes of cardiovascular (CV) disease, leading to high rates of mortality and morbidity. 1 Scientists, trying to identify possible pathophysiological pathways for hypertension‐mediated organ damages (HMOD), draw their attention to the correlation of hypertension with arterial stiffness. Arterial stiffness, measured either by pulse pressure (in older people) or by carotid‐femoral pulse wave velocity (c‐f PWV), is considered to be one of the main factors affecting CV risk in the hypertensive population and has been included to the detailed screening of patients with hypertension in latest ESC/ESH guidelines. 2 , 3 , 4
The different hypertension phenotypes seem to have a different effect on HMOD and especially on arterial stiffness. Except from normotension and hypertension, whose relation with HMOD is clear, there are other two hypertension phenotypes. White‐coat hypertension (WCH) is defined as elevated office blood pressure (BP) values, but normal BP values during either the 24 hours ambulatory BP monitoring (ABPM) or home measurements. 3 Οn the contrary, masked hypertension (MH) is characterized by normal office BP values, followed by elevated BP values during home or ABPM measurements. Both of these phenotypes may not be clinically innocent, having been correlated with higher rates of CV risk. 5 , 6
If we consider that WCH affects approximately 30% of the population with elevated office BP and MH the 15% of the population with normal BP, 3 it is not only important to diagnose these two conditions but also to investigate their association with HMOD in order to prevent them in time. Many studies have been performed at the field of hypertension phenotypes and give ambiguous results regarding the phenotypes’ impact on arterial stiffness. 7 , 8 To our knowledge, this is the first meta‐analysis showing the effect of MΗ and WCH on arterial stiffness in the untreated population. There is only one other meta‐analysis investigating the relation of WCH on c‐f PWV but in both treated and untreated patients, 9 whereas there is no similar published meta‐analysis for the MH population.
The aim of the present study was to systematically review in the literature and conduct a meta‐analysis in order to identify the association of the four hypertension phenotypes with subclinical arterial stiffness, specifically c‐f PWV, in an untreated population.
2. METHODS
This systematic review and meta‐analysis are performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. 10 All researches were conducted according to a protocol registered in the OFS database (available in https://osf.io/974gb/, https://doi.org/10.17605/OSF.IO/974GB).
2.1. Literature search strategy
A systematic search using Medline and Cochrane Library from inception to September 17, 2019, was performed to identify studies measuring c‐f PWV in the four phenotypes of hypertension. We used search terms that had been identified from initial scoping searches, target references, and browsing of database thesauruses (Appendix S1). PROSPERO was also checked to identify possible similar meta‐analysis in progress in order to avoid duplication with our study. Conference abstracts and references of relevant studies and systematic reviews were perused, and experts were contacted in order to identify unpublished studies.
2.2. Eligibility and exclusion criteria
We included original cross‐sectional studies measuring c‐f PWV (c‐f PWV measured by applanation tonometry and piezoelectric mechanotransducer) in the hypertension phenotypes, that is, normotension, MH, WCH, and sustained hypertension. PWV values have been evaluated according to the established reference values for arterial stiffness. 11 The out‐of‐office BP measurements should have been defined by ABPM. Finally, full articles published in peer‐reviewed journals were only included. The exclusion criteria were the following: (a) patients receiving antihypertensive drugs, (b) studies with less than 10 individuals in any arm, (c) other ways of measuring PWV (augmenation index, arterial elasticity, arterial compliance) or pulse wave velocity measured by different methods (MRI, ultrasound, oscillometry) or at different sites (aorta) or paths (branchial‐ankle), and (d) children population.
2.3. Data extraction and quality assessment in individual studies
The searches’ results were imported in a reference management software (EndNote X7 for Windows, Thomson Reuters). After removing the duplicate records, two reviewers (CA and PV) screened titles and abstracts independently and full texts were investigated for eligible studies. Differences between the two reviewers regarding study eligibility were resolved by a third reviewer (ID).
Study and population characteristics were extracted from each included study. Regarding study characteristics, the name of the first author, the year of publication, and the number of centers and countries contributing to the research as well as possible funding were extracted. Also, the number of patients, the population, and the primary outcome and details for possible matched characteristics were recorded. Finally, sex, age (years), body mass index (BMI, kg/m2), c‐f PWV (m/s), office systolic and diastolic BP (mm Hg) and 24 hours systolic and diastolic BP (mm Hg) were also extracted.
Two reviewers (CA and PV) evaluated potential risk of bias in included studies using the Newcastle‐Ottawa quality assessment scale (NOS) for cross‐sectional studies (details for the NOS are provided to the Appendix S2). 12
2.4. Data synthesis—Statistical analysis
Study estimates were pooled using an inverse variance weighting. The DerSimonian‐Laird estimate was used to calculate the between‐study variance. 9 A prediction interval for the phenotype effect of a new study was also calculated as proposed by Higgins. 13 All analyses were performed in R version 3.6, using the meta package. 14 , 15 Heterogeneity was tested with the Cochran chi‐square test and the degree of heterogeneity was quantified by the I 2 statistics and its 95% CI. All P‐values were two‐tailed at significance level of .05.
3. RESULTS
3.1. Search results and characteristics of included studies
Our search concluded to 2352 patients. Only seven studies met the inclusion criteria and finally were included in our meta‐analysis (Figure 1). 7 , 8 , 16 , 17 , 18 , 19 , 20 Most of the studies were conducted in Greece, whereas the other studies were conducted in Brazil, France, and Italy, being published between 2004 and 2019. Only three studies provided arterial stiffness details for all the hypertension phenotypes, 7 , 8 1 study compared only WCH with normotensives, 16 while one study compared WCH with both normotensives and sustained hypertensives. 18 The other two studies compared c‐f PWV in the MH and normotensive group and/or hypertensive group. 17 The cutoff values for office and out‐of‐office BP measurements are based on the guidelines of the European Society of Hypertension. 3 Details are provided at Appendix S3. The characteristics of the seven studies, included in our meta‐analysis, are shown in Table 1. The Newcastle‐Ottawa quality assessment scale scores of all studies are analyzed in Appendix S4 and ranged from 6 to 9.
Figure 1.
Summary of evidence search and selection
Table 1.
Summary of included studies, individual study details, findings, and overall risk assessment
| Author, Year | Country | N | Primary Outcome | Population Characteristics | Duration (mo) | Characteristics | PWV technique | NOS |
|---|---|---|---|---|---|---|---|---|
| Ormezzano et al, 2004 20 | France | 150 | Prevalence of MH Cardiovascular involvement of MH Cardiovascular parameters in NT and MH | Untreated | N/A | Adjusted values N/A | Complior (Colson) | 6 |
| Drager et al, 2010 17 | Brazil | 61 | Frequency of MH in obstructive sleep apnea PWV in obstructive sleep apnea | Untreated with obstructive sleep apnea | N/A | Age‐ and BMI‐matched without obstructive sleep apnea Adjusted values N/A | Complior (Colson, Garges les Gonesses, France) | 8 |
| Andrikou et al, 2011 7 | Greece | 291 | hs‐CRP and PWV in MH, WCH, HT | Untreated | 24 | Age‐ and sex‐matched normotensives Adjusted values N/A | Complior (Artech Medical, Pantin, France) | 9 |
| Schillaci et al, 2011 18 | Italy | 610 | PWV in NT, WCH, HT | Untreated | N/A | Not matched Adjusted values N/A | SpygmoCor Vx (ArtCor, Sydney, Australia) | 8 |
| Androulakis et al, 2017 16 | Greece | 387 | FMD, PWV, IMT, LVMI in WCH | Untreated | 48 | Not matched Adjusted values N/A | Complior (Artech Medical, Pantin, France) | 8 |
| Gkaliagkousi et al, 2018 19 | Greece | 311 | ADMA and vascular damage | Untreated | 48 | Age‐matched normotensives Adjusted values N/A | SphygmoCorTM (AtCor, Australia) | 9 |
| Antza et al, 2019 8 | Greece | 542 | PWV in NT, WCH, MH, TH | Untreated | 48 | Not matched Adjusted for age and sex | Complior (Colson) | 8 |
Abbreviations: ADMA: asymmetric dimethylarginine; BMI: body mass index; FMD, flow‐mediated dilation; hs‐CRP, high‐sensitivity C‐reactive protein; HT, hypertension; IMT, intima‐media thickness; LVMI, left ventricular mass index; MH, masked hypertension; NT, normotension; N/A, not available; PWV, pulse wave velocity; WCH, white‐coat hypertension.
3.2. Outcomes
The descriptive characteristics of the normotensive population are summarized in Table 2. All of the studies provided details for the normotensive population. The c‐f PWV in the normotensive population had a wide range, from 6.8 to 9.9 m/s. One of the highest values of c‐f PWV was noticed in the obstructive sleep apnea patients, who had also the highest BMI. 17 The sustained hypertensive population is described in four studies (Table 3). The c‐f PWV in the sustained hypertensive population ranged from 8.2 to 11.9 m/s.
Table 2.
Descriptive statistics of the normotensive population of each study
| Author, Year | N (%) | Sex (male,%) | Age ± SD (y) | BMI ± SD (m/kg2) | Office Systolic BP ± SD (mm Hg) | Office Diastolic BP ± SD (mm Hg) | 24 h Systolic BP ± SD (mmHg) | 24 h Diastolic BP ± SD (mm Hg) | PWV ± SD (m/s) |
|---|---|---|---|---|---|---|---|---|---|
| Ormezzano et al, 2004 20 | 51 (34%) | 33.3 | 47.8 ± 8.9 | 23.2 ± 3.4 | 119.2 ± 9.7 | 77.7 ± 7.1 | 119.7 ± 6.7 | 77.8 ± 4.9 | 8.6 ± 1.4 |
| Drager et al, 2010 17 | 30 (49.2) | 100 | 43 ± 7 | 29.1 ± 3.2 | 116 ± 9.9 | 72 ± 7 | 117 ± 7 | 74 ± 5 | 9.4 ± 1 |
| Andrikou et al, 2011 7 | 44 (15.1) | 61 | 52 ± 5 | 28.8 ± 5 | 122 ± 8 | 87 ± 8 | 115 ± 8 | 74 ± 11 | 6.8 ± 0.5 |
| Schillaci et al, 2011 18 | 71 (11.6) | 51 | 47 ± 10 | 27.3 ± 4 | 128 ± 7 | 78 ± 6 | 121 ± 10 | 75 ± 7 | 8.3 ± 2 |
| Androulakis et al, 2017 16 | 183 (47.3) | 39 | 52.4 ± 0.9 a | 27.4 ± 0.6 a | 131.3 ± 1 a | 83.1 ± 0.9 a | 113.9 ± 0.5 a | 67.8 ± 0.6 a | 7.6 ± 0.1 a |
| Gkaliagkousi et al, 2018 19 | 71 (22.8) | 54.9 | 43.1 ± 12.6 | 26.2 ± 3.9 | 119 ± 9.3 | 75.8 ± 7.3 | 116.3 ± 7.5 | 72.9 ± 5.7 | 6.8 ± 1.2 |
| Antza et al, 2019 8 | 239 (44) | 49.6 | 29.3 ± 15 | 24.1 ± 4.7 | 121.1 ± 10.6 | 73.9 ± 8.3 | 115.7 ± 9 | 69 ± 5.9 | 9.9 ± 0.2 |
Abbreviations: BP, blood pressure; N/A, not available; PWV, pulse wave velocity, SD, standard deviation.
Standard error.
Table 3.
Descriptive statistics of the sustained hypertensive population of each study
| Author, Year | N (%) | Sex (male,%) | Age ± SD (y) | BMI ± SD (m/kg2) | Office Systolic BP ± SD (mm Hg) | Office Diastolic BP ± SD (mm Hg) | 24 h Systolic BP ± SD (mm Hg) | 24 h Diastolic BP ± SD (mm Hg) | PWV ± SD (m/s) |
|---|---|---|---|---|---|---|---|---|---|
| Ormezzano et al, 2004 20 | 81 (54) | 58 | 51.3 ± 10.6 | 25.7 ± 4.1 | 151.4 ± 9.7 | 96.9 ± 6.3 | 147.8 ± 11.2 | 97 ± 8.8 | 10.3 ± 1.9 |
| Andrikou et al, 2011 7 | 178 (61.2) | 67 | 50 ± 8 | 29.3 ± 4 | 152 ± 14 | 98 ± 8 | 148 ± 10 | 89 ± 7 | 8.2 ± 1.4 |
| Schillaci et al, 2011 18 | 406 (66.6) | 63 | 49 ± 10 | 27.3 ± 4 | 154 ± 16 | 97 ± 9 | 134 ± 10 | 86 ± 7 | 9.7 ± 2 |
| Gkaliagkousi et al, 2018 19 | 165 (53) | 67.5 | 45.1 ± 11.3 | 28 ± 4.5 | 150.6 ± 15.4 | 95.2 ± 9.6 | 141.4 ± 12.2 | 89.8 ± 8.9 | 8.4 ± 1.7 |
| Antza et al, 2019 8 | 162 (30) | 49.4 | 56.6 ± 21.5 | 28.2 ± 4.7 | 160.5 ± 20.2 | 95.6 ± 16.5 | 149.8 ± 18.7 | 87 ± 9.9 | 11.9 ± 0.2 |
Abbreviations: BP, blood pressure; N/A, not available; PWV, pulse wave velocity; SD, standard deviation.
Table 4 summarizes the descriptive statistics of the WCH population from the five included studies. The prevalence of the WCH ranges from 8% to 57.1%. The c‐f PWV was ranged from 7.5 to 10.3 m/s, with the lowest values been observed in the population with the lowest values of 24 hours systolic BP. 7 Details about the MH population are provided in Table 5. The prevalence of the MH ranges from 6.8% to 21.3%, whereas c‐f PWV results have a wide range from normal to abnormal. 7 , 8 , 17 , 19
Table 4.
Descriptive statistics of the white‐coat hypertensive population of each study
| Author, Year | N (%) | Sex (male,%) | Age ± SD (y) | BMI ± SD (m/kg2) | Office Systolic BP ± SD (mm Hg) | Office Diastolic BP ± SD (mm Hg) | 24 h Systolic BP ± SD (mm Hg) | 24 h Diastolic BP ± SD (mm Hg) | PWV ± SD (m/s) |
|---|---|---|---|---|---|---|---|---|---|
| Andrikou et al, 2011 7 | 81 (27.8) | 63 | 52 ± 8 | 28.9 ± 4 | 146 ± 10 | 91 ± 8 | 119 ± 7 | 74 ± 11 | 7.5 ± 1.2 |
| Schillaci et al, 2011 18 | 133 (21.8) | 50 | 49 ± 12 | 27.5 ± 4 | 146 ± 11 | 89 ± 8 | 121 ± 6 | 74 ± 5 | 9.3 ± 2 |
| Androulakis et al, 2017 16 | 201 (57.1) | 47 | 54.3 ± 0.9 a | 28.5 ± 0.6 a | 152.9 ± 1 a | 92.9 ± 0.9 a | 120.1 ± 0.5 a | 71.4 ± 0.5 a | 8.6 ± 0.1 a |
| Gkaliagkousi et al, 2018 19 | 25 (8) | 57 | 46.7 ± 12.4 | 28.4 ± 5.3 | 143.5 ± 11.1 | 93.5 ± 6.1 | 120.3 ± 5.1 | 76.4 ± 4.9 | 8.2 ± 1.2 |
| Antza et al, 2019 8 | 105 (19.4) | 72 | 45 ± 23 | 29.1 ± 5.6 | 147.4 ± 14 | 89.5 ± 11.1 | 122.6 ± 8 | 73.1 ± 6.3 | 10.3 ± 0.3 |
Abbreviations: BP, blood pressure; N/A, not available; PWV, pulse wave velocity; SD, standard deviation.
Standard error.
Table 5.
Descriptive statistics of the masked hypertensive population of each study
| Author, Year | N (%) | Sex (male,%) | Age ± SD (y) | BMI ± SD (m/kg2) | Office Systolic BP ± SD (mm Hg) | Office Diastolic BP ± SD (mm Hg) | 24 h Systolic BP ± SD (mm Hg) | 24 h Diastolic BP ± SD (mm Hg) | PWV ± SD (m/s) |
|---|---|---|---|---|---|---|---|---|---|
| Ormezzano et al, 2004 20 | 18 (12) | 55.6 | 49.3 ± 9.4 | 24 ± 3.5 | 129 ± 6.6 | 83.1 ± 4.2 | 134.3 ± 5.5 | 87 ± 4.8 | 9.6 ± 1.6 |
| Drager et al, 2010 17 | 13 (21.3) | 100 | 47 ± 7 | 28.9 ± 2.5 | 123 ± 10 | 76 ± 10 | 127 ± 6 | 84 ± 3 | 10.6 ± 1.1 |
| Andrikou et al, 2011 7 | 32 (11) | 66 | 51 ± 9 | 27.9 ± 3.5 | 128 ± 7 | 88 ± 7 | 132 ± 15 | 85 ± 11 | 7.3 ± 0.9 |
| Gkaliagkousi et al, 2018 19 | 50 (16) | 50 | 44.1 ± 11.5 | 26.9 ± 3.8 | 129.1 ± 7.3 | 81.7 ± 6.5 | 130,7 ± 7.3 | 83 ± 6.6 | 7.5 ± 1.1 |
| Antza et al, 2019 8 | 37 (6.8) | 40.5 | 57.2 ± 26.2 | 27.1 ± 5.3 | 127.7 ± 6.6 | 67.8 ± 7.5 | 138.8 ± 9.6 | 80 ± 9.6 | 11.3 ± 0.5 |
Abbreviations: BP, blood pressure; N/A, not available; PWV, pulse wave velocity; SD, standard deviation.
When pooling the results of all included studies, MH and WCH patients had significantly increased c‐f PWV values compared to the normotensive groups, (d = 0.96 m/s, 95% CI: 0.49‐1.42; I 2 = 85%, P < .01 for MH, Figure 2 and d = 0.85 m/s, 95% CI: 0.48‐1.22; I 2 = 89%, P < .01 for WCH, Figure 3). On the other hand, the sustained hypertensive population was found to have significantly increased values of c‐f PWV compared to MH (d = −0.70 m/s, 95% CI: −0.87 to −0.54; I 2 = 12%, P = .33, Figure 4) but not compared to WCH population (d = −0.75 m/s, 95% CI: −1.52 to 0.02; I 2 = 96%, P < .01, Figure 5). Finally, there was no significant difference between MH and WCH population (d = 0.06 m/s, 95% CI: −1.04 to 1.15; I 2 = 96%, P < .01, Figure 6). In all analyses, the prediction intervals included zero values suggesting that in a future setting, a real difference might not exist.
Figure 2.
Forest plot of the mean differences of masked hypertensives to normotensives in carotid‐femoral pulse wave velocity
Figure 3.
Forest plot of the mean differences of white‐coat hypertensives to normotensives in carotid‐femoral pulse wave velocity
Figure 4.
Forest plot of the mean differences of masked hypertensives to sustained hypertensives in carotid‐femoral pulse wave velocity
Figure 5.
Forest plot of the mean differences of white‐coat hypertensives to sustained hypertensives in carotid‐femoral pulse wave velocity
Figure 6.
Forest plot of the mean differences of masked hypertensives to white‐coat hypertensives in carotid‐femoral pulse wave velocity
3.3. Subgroup and sensitivity analyses
Results for the significant difference between normotensives and MH remained similar (d = 0.88 m/s, 95% Cl: 0.25‐1.52; I 2 = 92.6%, P < .001) in a subgroup analysis after excluding the study of Drager et al. This decision is based on the fact that this population differs from the population of the other studies, including highly overweight patients with obstructive sleep apnea. 17 Sensitivity analysis was performed after excluding low‐quality studies (values higher or equal than 8 were taken into account as having a good/acceptable quality, based to the NOS). 20 In the sensitivity analysis, the difference between MH and normotensives remained statistically significant (d = 0.95 m/s, 95% CI: 0.42‐1.48; I 2 = 89%, P < .01, Appendix S5). The same was applied for the difference between MH and sustained hypertensives (d = −0.74 m/s, 95% CI: −0.96 to −0.52, I 2 = 41%, P = .18, Appendix S6).
4. DISCUSSION
This systematic review and meta‐analysis showed a clearly association of MH and WCH with arterial stiffness, as the MH and WCH population have statistically significant increased values of c‐f PWV compared to the normotensive group. Furthermore, the comparison between MH and WCH showed that these two phenotypes have a similar relationship with arterial stiffness. These results demonstrate that these phenotypes may not be clinically innocent, in the untreated population.
Evidence from a recent meta‐analysis shows that the WCH population presents alterations in both cardiac structure and function, having higher left ventricular mass index, lower mitral E/A ratio, and larger left atrium compared to the normotensive population. 21 Furthermore, it seems that WCH phenotype is correlated with higher risk of CV mortality and morbidity compared to the normotensive phenotype. 22 , 23 Cuspidi et al 24 investigated also the relationship between WCH and atherosclerotic changes showing again a statistically significant increase in carotid intima‐media thickness. Regarding MH, results are in the same direction. MH phenotype has a higher left ventricular mass index and higher values of carotid intima‐media thickness compared to normotensive phenotype. 24 , 25
Target organ damage and clinical outcomes have also been correlated with hemodynamic variables, including BP variability and cerebrovascular reactivity. Taking them into account could provide a more exhaustive assessment of the detrimental effects of altered BP and allow to explore potential differences across the clinical phenotypes. 26 , 27 , 28 The second point is that the difference with the normotensives might be an effect of the classification. For instance, the WCH group had a higher 24 hours ABPM than the normotensives, which can account for the observed PWV difference only on the basis of the 24 hours BP difference. Conversely, MH had a higher office BP. Thus, rather than an effect of the BP class, this seems to be the effect of a higher BP. Obviously, in a meta‐analytic study, this should be taken into account as one cannot match the different groups by BP.
This is the first study to evaluate the arterial damage, confirmed by c‐f PWV, on the four phenotypes of hypertension in untreated patients. There is another meta‐analysis, conducted by Cai et al, in which authors pooled the results for both treated and untreated patients in their effort to investigate the WCH population in relation to c‐f PWV. This effort raises queries about possible selection bias. 9 However, according to the latest guidelines of the ESC/ESH, these two phenotypes are mainly referred to patients not being treated with antihypertensive agents and now seem to be even more separated from the treated population as two terms now are introduced (the masked uncontrolled and the white‐coat uncontrolled hypertension accordingly for the treated population). 3
The present systematic review and meta‐analysis have both strengths and limitations. To the best of our knowledge, this is the first meta‐analysis to compare the four hypertension phenotypes for their association with arterial damage of large arteries in the untreated population. Heterogeneity was present in our analysis and could be accounted to the sample size ratios of patients and controls, age, disease duration, and metabolic characteristics. Moreover, this meta‐analysis included both matched and not matched studies. However, the forest plots were designed with an effective way for the readers to identify the matched/no matched primary studies. Finally, in the present meta‐analysis we included only observational studies, as there is no randomized control trial with that outcome. Given the paucity of data, meta‐analysis of good‐quality observational studies may offer enhanced level of evidence and point out research gaps for future research. Limitation of our study could be also the fact that we included studies evaluating c‐f PWV with different methods (Complior and SphygmoCor), but there was not enough evidence to conduct different analyses for each method.
Given that there is no randomized evidence, limited observational studies with adjusted analyses, the substantial heterogeneity in the results and the wide prediction intervals, the related findings should be interpreted with caution. The MH and WCH seem to be not clinically innocent and should be totally differentiated from normotension. As evidence become stronger, the possibility of treating those populations and the appropriate choice of treatment may be considered for further research. Until then, the results highly recommend an extensive but also intensive follow‐up of these patients, in well‐equipped hypertension centers. Finally, due to the high prevalence of MH and WCH and the correlation with target organ damages, the out‐of‐clinic BP measurements should be established in the untreated population.
In conclusions, this systematic review and meta‐analysis may show an association of MH and WCH with arterial damage, a result that came in accordance with the existing data supporting that these phenotypes are correlated with CV damage and mortality. 21 , 22 , 23 , 24 , 25
CONFLICT OF INTEREST
None.
AUTHOR CONTRIBUTIONS
CA: independent reviewer, proposed the structure of the paper and formulated the paper. PV: independent reviewer, extracted the data. ID and EB: performed the statistical analysis. ABH: supervised the statistical analysis and made final suggestions. SS critically appraised the paper and made final suggestions. VK: proposed the idea, critically appraised the paper, and made final suggestions.
Supporting information
Appendix S1‐S6
Antza C, Vazakidis P, Doundoulakis I, et al. Masked and white coat hypertension, the double trouble of large arteries: A systematic review and meta‐analysis. J Clin Hypertens. 2020;22:802–811. 10.1111/jch.13876
Registration number (DOI): Available in https://osf.io/974gb/, https://doi.org/10.17605/OSF.IO/974GB
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Supplementary Materials
Appendix S1‐S6