2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices.

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

How to check whether a blood pressure monitor has been properly validated for accuracy.

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non-validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non-validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country-specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross-checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.

Prevalence and clinical correlates of ambulatory blood pressure phenotypes in a Saudi hypertensive population.

International Guidelines recommend ambulatory blood pressure monitoring (ABPM) for the management of hypertension. ABPM phenotypes predict outcomes independent of office blood pressure (BP). The authors explored the prevalence and clinical correlates of ABPM phenotypes and relationship with office BP in Saudi patients (n = 428, mean age 53.5 ± 14.6, 55% male) referred to a Specialist Hypertension clinic in Riyadh, Saudi Arabia. ABPM phenotypes included sustained normotension (27%), masked hypertension, MHT(32%), sustained hypertension, SHT(52%), and white coat hypertension(2.6%). MHT was more prevalent using asleep than 24-hours (26.4% vs 12.9%, P < .01) or awake BP (26.4% vs 8.5%, P < .001) and observed in 85% of pre-hypertensive patients. Isolated nocturnal hypertension was more prevalent in MHT vs SHT (70% vs 30%, P < .001). Office BP overestimated control rates compared with ABPM (48% vs 12.9%, P < .001). Our study shows that one in three Saudi patients will be managed inappropriately if office BP alone was relied upon for management of hypertension.

Blood pressure-lowering activity of statins: a systematic literature review and meta-analysis of placebo-randomized controlled trials.

PURPOSE: To investigate the blood pressure (BP)-lowering effects of statins by conducting a systematic review and meta-analysis of placebo-randomized controlled trials (RCTs). METHOD: We conducted a meta-analysis of placebo RCTs reporting antihypertensive effects of statins therapy. We only included RCTs that did not allow for concomitant antihypertensive therapy, or clearly stated that antihypertensive therapy was fixed throughout the study period. RESULTS: Our meta-analysis included 46 placebo RCTs, including 53 group comparisons and a total of 49,087 participants (24,589 participants in the statin groups and 24,498 participants in the placebo group). Subgroup analysis, based on use of concomitant antihypertensive, was performed. The meta-analysis showed that statin reduced systolic BP by - 1.6 mmHg (95% CI: - 2.50 to - 0.60), and diastolic BP by - 0.96 mmHg (95% CI: - 1.36 to - 0.56). Although the presence of concomitant antihypertensive therapy diluted the BP lowering effect of statins, it remained statistically significant and independent of the lipid-lowering activity. Furthermore, the BP -lowering effect of the statins was independent of the dose or type of statin (p > 0.05). CONCLUSION: Our results strengthen the evidence for pleiotropic effects of statins on BP that are independent of their lipid-lowering activity, supporting their beneficial role in hypertensive patients with dyslipidemia.

Impact of the 2017 ACC/AHA guideline on the prevalence of elevated blood pressure and hypertension: a cross-sectional analysis of 10 799 individuals.

OBJECTIVES: To assess the effect of the 2017 American College of Cardiology and the American Heart Association (ACC/AHA) hypertension guideline on the prevalence of elevated blood pressure (BP) and hypertension and the initiation of antihypertensive treatment, as well as the level of adherence to the BP target in the Saudi population. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 10 799 adults (≥18 years old), with three BP readings during 2017-2020 from the Saudi Biobank was used. PRIMARY OUTCOME: Hypertension was defined using three sources: the Joint National Committee 7 Blood Pressure Guideline (JNC-7) guideline (systolic BP (SBP)≥140 or diastolic BP (DBP)≥90 mm Hg), the 2017 ACC/AHA guideline (SBP≥130 or DBP≥80 mm Hg) and a self-reported hypertension diagnosis. RESULTS: The prevalence of hypertension, according to the JNC-7 guideline, was 14.49% (95% CI 14.37 to 14.61), and the 2017 ACC/AHA, 40.77% (95% CI 40.60 to 40.94), a difference of 26.28%. Antihypertensive medication was recommended for 24.84% (95% CI 24.69 to 24.98) based on the JNC-7 guideline and 27.67% (95% CI 27.52 to 27.82) using the 2017 ACC/AHA guideline. Lifestyle modification was recommended for 13.10% (95% CI 12.47 to 13.74) of patients with hypertension who were not eligible for a pharmacological intervention, based on the 2017 ACA/AHA guideline. For patients with prescribed antihypertensive medication, 49.56% (95% CI 45.50 to 53.64) and 27.81% (95% CI 24.31 to 31.59) presented with a BP reading above the treatment goal, based on the 2017 ACA/AHA and JNC-7 guidelines, respectively. Using the two definitions, the risk factors were older age, male gender, diabetes diagnosis, increased body mass index, waist circumference and waist-to-hip ratio. CONCLUSIONS: According to the 2017 ACC/AHA guideline, the prevalence of hypertension has increased significantly, but there was only a small increase in the proportion of patients recommended for antihypertensive treatment. A large proportion of patients with prescribed antihypertensive medication, had a BP above the target. Unless public health prevention efforts are adopted, the increased prevalence of elevated BP and hypertension will increase cardiovascular disease.

Inverse relationship between physical activity and arterial stiffness in adults with hypertension.

BACKGROUND: Physical activity has beneficial effects on arterial stiffness among healthy adults. There is a lack of data on this relationship in adults with hypertension. The majority of studies which have examined physical activity and arterial stiffness have used subjective measures of activity. The aim of this study was to investigate the relationship between objectively measured habitual physical activity and arterial stiffness in individuals with newly diagnosed essential hypertension. METHODS: Adults attending an outpatient hypertension clinic were recruited into this cross sectional study. Physical activity was measured using a triaxial accelerometer. Pulse wave velocity (PWV) and augmentation index (AIx) were measured using applanation tonometry. Participant's full lipid profile and glucose were determined through the collection of a fasting blood sample. RESULTS: Fifty-three adults [51(14) years, 26 male] participated, 16 of whom had the metabolic syndrome. Inactivity was positively correlated with PWV (r = .53, P < .001) and AIx (r = .48, P < .001). There were significant inverse associations between habitual physical activity of all intensities and both AIx and PWV. In stepwise regression, after adjusting for potential confounders, physical activity was a significant predictor of AIx and PWV. CONCLUSION: Habitual physical activity of all intensities is associated with reduced arterial stiffness among adults with hypertension.

Postprandial effect of dietary fat quantity and quality on arterial stiffness and wave reflection: a randomised controlled trial.

BACKGROUND: Arterial stiffness is a component of vascular function and an established risk factor for cardiovascular disease. There is a lack of conclusive evidence on the effect of a meal rich in monounsaturated fat (MUFA) compared with an isoenergetic meal rich in saturated fat (SFA) on postprandial vascular function and specifically on arterial stiffness. METHODS: Twenty healthy, non-smoking males (BMI 24 ± 2 kg/m2; age 37.7 ± 14.4 y) participated in this single-blind, randomised, cross-over dietary intervention study. Each subject was randomised to receive a high-fat test-meal (3 MJ; 56 ± 2 g fat) at breakfast on 2 separate occasions, one rich in oleic acid (MUFA-meal) and one rich in palmitic acid (SFA-meal), and the meals were isoenergetic. Blood pressure (BP), arterial stiffness (PWV) and arterial wave reflection (augmentation index, AIx) were measured using applanation tonometry at baseline and every 30 minutes up to 4 hours after the ingestion of the test-meals. RESULTS: All subjects completed both arms of the dietary intervention. There was no significant difference in BP parameters, PWV or AIx at baseline between the two treatments (P > 0.05). There was a significant increase in brachial and aortic BP, mean arterial pressure (MAP), heart rate and PVW (time, P < 0.05) over the four hours after consumption of the fat-rich test-meal although the increase in PWV was no longer significant when adjusted for the increase in MAP. There was no difference in PWV between the two treatments (treatment*time, P > 0.05). There was a significant reduction in AIx (time, P < 0.05) over the four hour postprandial period although this was no longer significant when adjusted for the increase in heart rate and MAP (time, P > 0.05). There was no difference in AIx between the two treatments (treatment*time, P > 0.05). However, the reduction in heart rate corrected augmentation index (AIx75) was significant when corrected for the increase in MAP (time, P < 0.01) with no differential effect of the treatments (treatment*time, P > 0.05). CONCLUSIONS: This study has demonstrated a BP dependent increase in PWV and a decrease in arterial wave reflection in the four hour period in response to a high-fat meal. There was no evidence however that replacement of some of the SFA with MUFA had a differential effect on these parameters. The study highlights the need for further research to understand the effects of the substitution of SFA with MUFA on non-serum, new and emerging risk factors for CVD such as arterial stiffness.

Pharmacological modulation of arterial stiffness.

Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for 'de-stiffening drugs', so far only advanced glycation endproduct cross-link breakers have shown promise.

Relations between large artery structure and function and aldosterone.

Aldosterone influences independently the vascular environment in humans, acting through structural and functional modifications of the arterial wall as derived from mineralocorticoid receptors. In rats, aldosterone infusion increases arterial stiffness in the presence of high-sodium intake, together with development of extracellular matrix and inflammatory factors. A selective increase in systolic and pulse pressure ensues, causing predominant organ damage on the heart, kidney and large arteries. In humans at rest, but independently of mean arterial pressure, arterial stiffness and wave reflections are associated with a steeper increase in these parameters with age. This finding is observed mainly with the CC genotype and not the TT or the TC genotype of the aldosterone synthase gene polymorphism. Early identification of individuals presenting this genotype could be important to detect hypertension.

Ventricular activation time as a marker for diastolic dysfunction in early hypertension.

BACKGROUND: A standard 12-lead electrocardiogram (ECG) is performed in all hypertensive patients, primarily to detect left ventricular hypertrophy. Echocardiographic assessment of hypertensive subjects reveals that abnormalities in diastolic function occur more commonly and earlier than increased left ventricular mass. However, ECG changes associated with diastolic dysfunction (DD) remain poorly defined; we assessed the ventricular activation time (VAT) (i.e., the time for the ventricle to depolarize) as a potential marker for DD in early hypertension. METHODS: Ninety subjects (aged 46 +/- 1.3 years; 43 men) with newly diagnosed, untreated hypertension underwent ECG and comprehensive two-dimensional echocardiography. Left ventricular DD was echocardiographically assessed using Canadian Consensus Guidelines. We compared VAT, which corresponds to the QR interval in the 12-lead ECG, with echocardiographic parameters of DD. RESULTS: VAT was prolonged in subjects with DD (46.3 +/- 0.4 vs. 39.6 +/- 0.3 ms, P < 0.01). There was a significant correlation between VAT and tissue Doppler imaging (TDI) (early diastolic velocity) e' (r = -0.53, P < 0.0001), (ratio of early and late diastolic velocities) e'/a' (r = -0.53, P < 0.0001), transmitral Doppler (TMD) (early peak filling rate, and early deceleration peak) E/A (r = -0.32, P = 0.001), and (ratio of early diastolic mitral inflow and early diastolic velocities) E/e' (r = 0.44, P < 0.0001). CONCLUSION: Prolongation of the VAT is associated with DD in patients with newly diagnosed untreated hypertension.

Assessment of arterial stiffness in hypertension: comparison of oscillometric (Arteriograph), piezoelectronic (Complior) and tonometric (SphygmoCor) techniques.

BACKGROUND: Arterial stiffness, measured as aortic pulse wave velocity (PWV), and wave reflection, measured as augmentation index (AIx), are independent predictors for total and cardiovascular morbidity and mortality. The aim of this study was to compare a new device, based on oscillometric pressure curves (Arteriograph), which simultaneously measures PWV and AIx, with standard techniques for measuring PWV (Complior) and AIx (SphygmoCor) in untreated hypertensive patients. METHODS: We compared PWV and AIx measured using the Arteriograph with corresponding Complior and SphygmoCor measurements in 254 untreated hypertensive patients, age 48 +/- 14 years (mean +/- SD, range 17-85 years). RESULTS: Arteriograph PWV and AIx were closely related with Complior (r = 0.60, P < 0.001) and SphygmoCor (r = 0.89, P < 0.001), respectively. Using stepwise regression analysis, the independent determinants of Arteriograph PWV were age, mean arterial pressure, heart rate and sex (r(2) = 0.44, P < 0.0001) and for AIx were age, weight, mean arterial pressure, heart rate and sex (r(2) = 0.65, P < 0.0001). The bias between the different techniques was determined by age and sex for PWV and age, body weight, sex, heart rate and mean arterial pressure for AIx. Bland-Altman plots showed that although the techniques were closely related, the limits of agreement were wide. CONCLUSION: Although Arteriograph values and the determinants of PWV and AIx are in close agreement with corresponding parameters obtained by Complior and SphygmoCor, respectively, the techniques are not interchangeable.

Blood pressure control determines improvement in diastolic dysfunction in early hypertension.

BACKGROUND: Diastolic dysfunction is common in early hypertension. We hypothesized that improvement in diastolic dysfunction is blood pressure (BP) dependent and may occur early with treatment in newly diagnosed untreated hypertensive patients. METHODS: Forty untreated hypertensive subjects (age 52 +/- 1.4 years, mean +/- s.e.m.) with diastolic dysfunction based on Canadian Consensus Guidelines, received either bendroflumethiazide 2.5 mg (1.25 mg for the first month), or candesartan 16 mg (8 mg for the first month). Left ventricular (LV) structure and function, early diastolic velocity (E') and systolic velocity, and systolic myocardial velocity (Sm) were assessed echocardiographically using M-mode, 2-dimensional, and tissue Doppler imaging (TDI) before and at 1 and 3 months following treatment. RESULTS: Antihypertensive treatment reduced BP significantly at 3 months (168 +/- 2/97 +/- 1-143 +/- 2/86 +/- 1 mm Hg, P < 0.0001). Both drugs had similar and significant effects on TDI E' which increased from 7.8 +/- 0.2 to 10 +/- 0.3 cm/s (P < 0.001). The improvement in TDI E' was independent of LV mass index (LVMI) regression but was significantly related to the improvement in Sm (r = 0.73, P < 0.0001) and the fall in systolic BP (R = 0.51, P < 0.001). Normalization of diastolic function was associated with better control of BP (130 +/- 4/81 +/- 2 mm Hg vs. 149 +/- 2/88 +/- 1 mm Hg, P < 0.05). In a stepwise regression model, reduction in systolic BP (P < 0.001) and TDI Sm (P < 0.0001) emerged as independent determinants of improvement in TDI E' with no contribution from age, gender or change in relative wall thickness (RWT) (R(2) = 0.68, P < 0.0001). CONCLUSIONS: Achieving good BP control and enhancement in systolic function determines the improvement in diastolic function in early hypertension.

Left ventricular structural and functional changes in the metabolic syndrome.

To test the hypothesis that the cardiac structural and functional abnormalities of the metabolic syndrome (MS) are independent of body mass index (BMI), 160 untreated patients (aged 47+/-1 years [mean +/- SEM], 53% male) underwent 2-dimensional echocardiography and tissue Doppler imaging and evaluation for MS. Participants with MS and controls were similar in age, BMI, and ejection fraction, but those with MS had greater left ventricular relative wall thickness (RWT) (0.43+/-0.008 vs 0.39+/-0.005, P<.001), reduced midwall fractional shortening (MFS) (13%+/-0.3% vs 14.2%+/-0.3%, P<.05), and reduced peak mitral annular velocity (Em) (9.9+/-0.5 vs 12.3+/-0.5 cm/sec, P<.01) than controls. There was a linear relationship between the number of features of MS and Em velocity (P<.001), RWT (P<.001), and MFS (P<.05). In a stepwise multiple regression analysis adjusting for likely determinants, MS was an independent predictor of Em in addition to age and nonindexed left ventricular mass. MS is associated with left ventricular concentric remodeling and reduced systolic and diastolic function independent of BMI.

Beta-blockers reduce aortic stiffness in hypertension but nebivolol, not atenolol, reduces wave reflection.

BACKGROUND: There is conflicting information with regard to the effect of beta-blockers on arterial stiffness and wave reflection. We compared a vasodilating beta-blocker, nebivolol, with atenolol. METHODS: We randomized 40 subjects with untreated hypertension (mean +/- s.e.m. systolic/diastolic blood pressure (BP) of 160 +/- 3/98 +/- 1 mm Hg, age 49 +/- 1 years) 16 of whom were women, to atenolol 50 mg or nebivolol 5 mg daily for 4 weeks. Arterial stiffness was assessed in terms of carotid-femoral pulse wave velocity (PWV, Complior) and arterial wave reflection (augmentation index (AIx) by applanation tonometry, Sphygmocor). RESULTS: Both beta-blockers produced an equal reduction in brachial BP but aortic pulse pressure (PP) was reduced to a greater extent by nebivolol (P < 0.05). PWV was decreased significantly by both therapies (nebivolol: from 11.5 +/- 0.5 to 9.9 +/- 0.5 m/s; atenolol: from 11.1 +/- 0.4 to 9.8 +/- 0.4 m/s; P < 0.01) but only nebivolol significantly reduced AIx (from 35 +/- 5 to 28 +/- 2%, P < 0.05). In addition, whereas PP amplification (PP, mm Hg) decreased with atenolol therapy (from 10 +/- 1 to 7 +/- 1, P < 0.01), it increased with nebivolol therapy (from 8 +/- 1 to 14 +/- 3, P < 0.01). Atenolol reduced heart rate to a greater extent than nebivolol did (14 +/- 3/min reduction by atenolol vs. 8 +/- 2/min reduction by nebivolol, P < 0.05). There was no difference between the two treatments in respect of the effect on transit time. CONCLUSION: The beta-blockers, atenolol and nebivolol, have a similar effect in reducing arterial stiffness in the large elastic aorta, largely secondary to BP reduction. Nebivolol, in contrast to atenolol, has an effect on small muscular arteries, increasing PP amplification and reducing wave reflection, possibly because of increased levels of nitric oxide (NO). Such ancillary properties may impart important distinct hemodynamic effects, and therefore beta-blockers cannot be regarded as a homogeneous group.

Ambulatory arterial stiffness index, pulse wave velocity and augmentation index--interchangeable or mutually exclusive measures?

BACKGROUND: The ambulatory arterial stiffness index (AASI) has been proposed as a novel measure of arterial stiffness and has been prospectively shown to predict stroke and cardiovascular death, but not cardiac death. This index has prompted considerable controversy as to whether it is a true measure of arterial stiffness. OBJECTIVE AND METHODS: The present study aimed to examine three different measures of arterial stiffness - pulse wave velocity (PWV; Complior), wave reflection [augmentation index (AIx)] and AASI - in a large hypertensive population, comparing their determinants and intercorrelations, both unadjusted and adjusted for confounders, and using Bland-Altman analysis to determine 95% confidence intervals for the ability of the AASI to predict PWV, the proposed gold standard of arterial stiffness. RESULTS: The AASI correlated univariately with both PWV and the AIx in individuals overall (r = 0.28 for PWV and r = 0.24 for AIx; both P < 0.001) and in those with untreated or treated hypertension. Adjustment for age in the current study negated entirely the positive correlation between the AASI, PWV and AIx. Additional adjustment for confounders did not significantly alter these nonsignificant relationships. Furthermore, the 95% prediction limits for the AASI to predict PWV were +/- 4.18 m/s and for the AASI to predict AIx were +/- 25.4%, suggesting that the methods would not be interchangeable in a clinical setting. Direct comparative studies would be required to establish the relative predictive strength of each measure and whether combining measures can provide additional risk prediction. Until such data become available, we propose that the measures should not be considered interchangeable.

History of gestational hypertension is associated with the metabolic syndrome and masked hypertension but not arterial stiffness in women with essential hypertension.

The underlying mechanisms of subsequent increased risk of cardiovascular disease with a history of gestational hypertension (GH) are not known. Untreated hypertensive women (n=155, age 43+/-1 years) underwent ambulatory blood pressure (BP) monitoring and assessment of aortic pulse wave velocity (PWV) and augmentation index (AIx). Despite identical clinic BP readings, the group of women with GH (n=54) had higher (P=.002) ambulatory daytime systolic BP levels and a greater number of extreme nocturnal dippers (P=.005) than the group without GH. Women with GH had higher body mass index (P=.003), greater waist circumference (P=.02), higher levels of triglycerides (P=.002), lower levels of high-density lipoprotein cholesterol (P=.004), a higher prevalence of the metabolic syndrome (P<.05) and microalbuminuria (P=.004), higher plasma renin activity (P=.03), and higher aldosterone levels (P=.01). There was no significant difference in PWV and AIx between the 2 groups. The higher prevalence of the metabolic syndrome, microalbuminuria, masked hypertension, and activation of the renin-angiotensin-aldosterone system but not arterial stiffness may explain the subsequent propensity to high BP and cardiovascular disease in women with GH.