The Role of Vascular Smooth Muscle Cells in Arterial Remodeling:Focus on Calcification-Related Processes

Arterial remodeling refers to the structural and functional changes of the vessel wall that occur in response to disease, injury, or aging. Vascular smooth muscle cells (VSMC) play a pivotal role in regulating the remodeling processes of the vessel wall. Phenotypic switching of VSMC involves oxidative stress-induced extracellular vesicle release, driving calcification processes. The VSMC phenotype is relevant to plaque initiation, development and stability, whereas, in the media, the VSMC phenotype is important in maintaining tissue elasticity, wall stress homeostasis and vessel stiffness. Clinically, assessment of arterial remodeling is a challenge; particularly distinguishing intimal and medial involvement, and their contributions to vessel wall remodeling. The limitations pertain to imaging resolution and sensitivity, so methodological development is focused on improving those. Moreover, the integration of data across the microscopic (i.e., cell-tissue) and macroscopic (i.e., vessel-system) scale for correct interpretation is innately challenging, because of the multiple biophysical and biochemical factors involved. In the present review, we describe the arterial remodeling processes that govern arterial stiffening, atherosclerosis and calcification, with a particular focus on VSMC phenotypic switching. Additionally, we review clinically applicable methodologies to assess arterial remodeling and the latest developments in these, seeking to unravel the ubiquitous corroborator of vascular pathology that calcification appears to be

Baroreflex Activation Therapy for the Treatment of Drug-Resistant Hypertension: New Developments

In the past few years, novel accomplishments have been obtained in carotid baroreflex activation therapy (BAT) for the treatment of resistant hypertension. In addition, this field is still evolving with promising results in the reduction of blood pressure and heart rate. This overview addresses the latest developments in BAT for the treatment of drug-resistant hypertension. Although not totally understood considering the working mechanisms of BAT, it appeared to be possible to achieve at least as much efficacy of single-sided as bilateral stimulation. Therefore unlike the first-generation Rheos system, the second-generation Barostim neo operates by unilateral baroreflex activation, using a completely different carotid electrode. Also significant improvements in several cardiac parameters have been shown by BAT in hypertensive patients, which set the basis for further research to evaluate BAT as a therapy for systolic heart failure. Yet important uncertainties need to be clarified to guarantee beneficial effects; hence not all participants seem to respond to BAT

The applicability of home blood pressure measurement in clinical practice: A review of literature

Willem J Verberk, Abraham A Kroon, Heidi A Jongen-Vancraybex, Peter W de LeeuwUniversity Hospital Maastricht, Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The NetherlandsPurpose: To review the literature on home blood pressure measurement (HBPM), to examine its validity and applicability for clinical practice and to provide recommendations regarding HBPM assessment.Findings: HBPM can eliminate the white coat effect and offers the possibility to obtain multiple measurements under standardized conditions, which increases knowledge of overall blood pressure value. Although it is not entirely capable of replacing ambulatory blood pressure measurement (ABPM), HBPM correlates better with target organ damage and cardiovascular mortality than office blood pressure measurement (OBPM), it enables prediction of sustained hypertension in patients with borderline hypertension, and proves to be an appropriate tool for assessing drug efficacy. Additional advantages of HBPM are that it may increase drug compliance and patient’s awareness of hypertension. Overall, OBPM yield higher blood pressure values than HBPM. Differences between OBPM and HBPM tend to increase with age and are generally higher in patients without antihypertensive treatment than in patients with antihypertensive treatment.Recommendations: Measurements should be performed according to accepted guidelines and recordings should be performed with a memory equipped automatic validated device. From the data reviewed here, we recommend that HBPM be assessed monthly by taking two measurements in the morning within 1 hour after awakening and two in the evening for three consecutive days, the data from the first day should be dismissed. A subject should be labeled hypertensive if his/her HBPM value is equal to or greater than 137 mmHg systolic and/or 84 mmHg diastolic.Keywords: blood pressure, hypertension, self-measurement, home measurement, ambulatory measurement, adherenc

Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD

Pressure-dependence of arterial stiffness: potential clinical implications

Background: Arterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age. Methods: Using a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80mmHg) pressure ranges. Results: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings. Conclusion: Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements

Using out-of-office blood pressure measurements in established cardiovascular risk scores: implications for practice

YesAbstract Background: Blood pressure (BP) measurement is increasingly carried out through home or ambulatory monitoring, yet existing cardiovascular risk scores were developed for use with measurements obtained in clinic. Aim: To describe differences in cardiovascular risk estimates obtained using ambulatory or home BP measurements instead of clinic readings. Design and setting: Secondary analysis of data from adults aged 30-84 without prior history of cardiovascular disease (CVD) in two BP monitoring studies (BP-Eth and HOMERUS). Method: The primary comparison was Framingham risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements. The QRISK2 and SCORE risk equations were also studied. Statistical and clinical significance were determined using the Wilcoxon signed-rank test and scatter plots respectively. Results: In 442 BP-Eth patients (mean age = 58 years, 50% female) the median absolute difference in 10-year Framingham cardiovascular risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements was 1.84% (interquartile range 0.65 to 3.63, p=0.67). Only 31/ 442 (7.0%) of patients were reclassified across the 10% risk treatment threshold. In 165 HOMERUS patients (mean age = 56 years, 46% female) the median difference in 10-year risk was 2.76% (IQR 1.19 to 6.39, p<0.001) and only 8/165 (4.8%) of patient were reclassified. Conclusion: Estimates of cardiovascular risk are similar when calculated using BP measurements obtained as in the risk score derivation study or through ambulatory monitoring. Further research is required to determine if differences in estimated risk would meaningfully influence risk score accuracy

Differences in renal hemodynamics and renin secretion between patients with unifocal and multifocal fibromuscular dysplasia

Objective: Fibromuscular dysplasia (FMD) can be classified in a multifocal and a unifocal subtype. As unifocal FMD generally leads to more severe hypertension at younger age, we hypothesized that renal hemodynamics are more disturbed in unifocal renal artery FMD as compared with multifocal FMD, leading to increased renin secretion. Methods: We measured renal blood flow ((133)Xenon washout method), renin secretion, and glomerular filtration rate per kidney in 101 patients with FMD (26 unifocal and 75 multifocal), all off medication and prior to balloon angioplasty. Results: We found that renal blood flow and glomerular filtration were substantially lower in kidneys with unifocal FMD as compared with multifocal FMD. In the affected kidney from patients with unilateral FMD for example, mean renal blood flow was 173 +/- 77 in unifocal vs. 244 +/- 79 ml/100 g kidney/min in multifocal FMD (P=0.013). Moreover, lateralization in renin secretion was only observed in a subset of patients with unifocal FMD, but not in any of the patients with multifocal FMD. Conclusion: These findings suggest that the impact of unifocal FMD lesions on the kidney is more severe, resulting in a classical pattern of renovascular hypertension. In multifocal FMD, however, renal blood flow is more preserved, local renin secretion is not increased, and the association between renin levels and blood pressure is inverse. These differences may explain the often more severe clinical presentation and higher success rate of revascularization in unifocal FMD, but also suggest that the pathophysiological mechanisms leading to hypertension may differ between these two disease entities

Greater Blood Pressure Variability Is Associated With Lower Cognitive Performance:The Maastricht Study

An increasing number of individuals will face age-related cognitive difficulties because life expectancy has increased. It is, therefore, important to identify modifiable risk factors for cognitive impairment. Very short-term to mid-term blood pressure variability (BPV) may be such a factor because it may cause cerebral ischemia. To this end, we investigated whether greater systolic and diastolic BPV are cross-sectionally associated with memory function (n=1804), information processing speed (n=1793), and executive function (n=1780) in 40- to 75-year-old individuals from The Maastricht Study. A composite BPV-index was derived by standardizing within-visit, 24-hour, and 7-day BPV. We performed linear regression with adjustments for age, sex, educational level, 24-hour systolic or diastolic pressure, and cardiovascular risk factors. We found that a 1-SD greater systolic BPV was not associated with information processing speed (β [SD difference], -0.10; 95% CI, -0.14 to 0.06), or executive function (-0.09; 95% CI, -0.20 to 0.02) but was marginally associated with lower memory function (-0.11; 95% CI, -0.21 to 0.00). A 1-SD greater diastolic BPV was associated with lower information processing speed (-0.10; 95% CI, -0.20 to -0.00) and executive function (-0.12; 95% CI, -0.22 to -0.01) and marginally associated with lower memory function (-0.09; 95% CI, -0.20 to 0.01). These effects on cognitive performance are equivalent to ≈3 additional years of aging. In conclusion, greater very short-term to mid-term diastolic and, to a lesser extent, systolic BPV may be a modifiable risk factor for cognitive deterioration in 40- to 75-year-old, community-dwelling individuals