Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy," which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy.

https://journals.physiology.org/doi/pdf/10.1152/physrev.00030.2020

Obesity Cardiomyopathy: Evidence, Mechanisms and Therapeutic Implications.

Nebivolol is a highly selective β1-adrenergic receptor antagonist with a pharmacologic profile that differs from those of other drugs in its class. In addition to cardioselectivity mediated via β1 receptor blockade, nebivolol induces nitric oxide-mediated vasodilation by stimulating endothelial nitric oxide synthase via β3 agonism. This vasodilatory mechanism is distinct from those of other vasodilatory β-blockers (carvedilol, labetalol), which are mediated via α-adrenergic receptor blockade. Nebivolol is approved for the treatment of hypertension in the US, and for hypertension and heart failure in Europe. While β-blockers are not recommended within the current US guidelines as first-line therapy for treatment of essential hypertension, nebivolol has shown comparable efficacy to currently recommended therapies in lowering peripheral blood pressure in adults with hypertension with a very low rate of side effects. Nebivolol also has beneficial effects on central blood pressure compared with other β-blockers. Clinical data also suggest that nebivolol may be useful in patients who have experienced erectile dysfunction while on other β-blockers. Here we review the pharmacological profile of nebivolol, the clinical evidence supporting its use in hypertension as monotherapy, add-on, and combination therapy, and the data demonstrating its positive effects on heart failure and endothelial dysfunction.

/pdf/a-review-of-nebivolol-pharmacology-and-clinical-evidence-3pmg3ee5qe.pdf

A Review of Nebivolol Pharmacology and Clinical Evidence

Objective:To identify vascular phenotypes across blood pressure (BP) conditions in overweight and obese youths, by assessing office BP (oBP), and central BP (cBP), and pulse pressure (PP) amplification. Whether or not 24-h ambulatory BP monitoring (ABPM) and pulse wave velocity (PWV) add insight to

Central blood pressure and pulse wave amplification across the spectrum of peripheral blood pressure in overweight and obese youth.

https://www.onlinecjc.ca/article/S0828-282X(14)00148-2/pdf

Central blood pressure as an index of antihypertensive control: determinants and potential value

Background. Pulse pressure (PP) amplification expressed as the peripheral-to-central PP ratio has gained importance in the assessment of cardiovascular phenotypes and cardiovascular risk. The aim of the present study was to assess the relationship between PP amplification, large vessel parameters and peripheral blood pressure (BP) to gain insights into the amplification phenomenon. Methods. Peripheral BP, central BP and carotid-femoral pulse wave velocity (cfPWV) were assessed using the OMRON M6, SphygmoCor and Complior devices, respectively, in 741 adults attending the hypertension outpatient clinic. Analysis of covariance, partial correlations and multiple linear regression models were performed to assess the relationship between PP amplification, peripheral BP and cfPWV. Results. PP amplification was inversely related to BP group. Women showed lower PP amplification than men (1.24 ± 0.18 and 1.35 ± 0.18, respectively, p < 0.001). Age, female gender and mean arterial pressure were inversely associated w...

Pulse pressure amplification and its determinants

BACKGROUND Obesity is an important risk factor for cardiovascular disease and has become a major concern in healthcare due to its high prevalence worldwide. The aim of the present study was to investigate the impact of BMI on central blood pressure (BP) and pulse wave velocity (PWV) in normotensive and hypertensive patients. PATIENTS AND METHODS Normotensive and hypertensive adult patients who attended the outpatient clinic of cardiovascular risk were included. Peripheral BP was obtained in the brachial artery by using an oscillometric device (OMRON M-6). Central aortic BP waveform was reconstructed from the radial artery pressure waveforms (SphygmoCor, AtCor Medical, Sydney, Australia) and central BP was calculated. Carotid-femoral PWV was measured by an automatic device (Complior, Artech, France). RESULTS We examined a total of 351 patients [50.7% women; 77 patients normal-weight (BMI < 25 kg/m)], 274 patients overweight or obese (BMI ≥25 kg/m). Central SBP showed a positive association with male sex and mean BP, but a negative association with overweight/obesity. PWV was positively associated with age, male sex, central BP, peripheral BP and BP treatment, whereas BMI of at least 25 kg/m led to a decrease in PWV in patients with the same central SBP levels. Likewise, PWV was lower in the overweight/obese group compared to the normal-weight group at the same central SBP. CONCLUSION Overweight and obesity tend to have lower central SBP as compared to lean patients, mainly in women. Further research is required to assess the interaction between body weight and vascular dynamics and their clinical implications.

Influence of obesity in central blood pressure.

Aims Myocardial fibrosis is a relevant component of hypertensive heart disease (HHD). Novel cardiovascular magnetic resonance (CMR) imaging techniques have shown potential in quantification of diffuse cardiac fibrosis, with T1 mapping, and estimating preclinical cardiac dysfunction, with strain analysis. Molecular biomarkers of fibrosis have been related with clinical outcomes and histologically proven myocardial fibrosis. The relationship between these CMR-imaging techniques and circulating biomarkers is not fully understood. Methods and results CMR was performed on a 3T scanner in 36 individuals with HHD. Extracellular volume fraction (ECV) and the partition coefficient were assessed using the T1 mapping technique shMOLLI. Longitudinal, circumferential and radial strain was assessed using CMR-Feature Tracking. Molecular biomarkers of collagen synthesis (PICP and PIIINP) and collagen degradation (CITP and MMP-1) were measured in blood using commercial kits. Correlation models showed a significant relationship of T1 mapping measures with left atrial diameter, LV mass, LV posterior wall thickness, LV end-diastolic volume and longitudinal strain. In fully adjusted regression models, ECV was associated with left atrial diameter (β=0.75, P = 0.005) and longitudinal strain (β = 0.43, P = 0.030); the partition coefficient was associated with LV posterior wall thickness (β = 0.53, P = 0.046). Strain measures were associated with cardiac geometry, and longitudinal strain was marginally associated with CITP. Conclusion In individuals with HHD, CMR-derived measures of myocardial fibrosis and function are related and might be useful tools for the identification and characterization of preclinical cardiac dysfunction and diffuse myocardial fibrosis. Molecular biomarkers of fibrosis were marginally associated with myocardial strain, but not with the extension of CMR-measured cardiac fibrosis.

Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease.

Introduction. The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol. Methods. Multicenter, double-blind randomized study conducted in six Spanish centers. We enrolled outpatients between the ages of 40 and 65 years with mild or moderate essential hypertension (systolic blood pressure, SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure, DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period). Patients received nebivolol 5 mg or atenolol 50 mg once daily. At week 3, atenolol could be titrated up to 100 mg qd for non-responders. Additionally, patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide. Follow-up visits were at 3, 6 and 10 weeks. Results. The final study population of 138 patients (58% men; median age 52.6 years, range 40–67 years) was randomized into two groups of 69 patients each. Baseline characteristics of the two groups were similar. At the...

Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: A multicenter, randomized, double-blind study

INTRODUCTION Several devices are available for carotid-femoral pulse wave velocity (cfPWV) measurement, and a cut-off value for reference cfPWV has been established. However, discrepancies between devices have been reported. OBJECTIVES The aim of the study was to establish the concordance of two common techniques (Complior and SphygmoCor), taking into account the anatomical distance between the measurement sites, and to investigate the impact on cardiovascular risk stratification. METHODS cfPWV, central and peripheral blood pressure were assessed in patients attending the hypertension outpatient clinic. The subtracted carotid-femoral distance was estimated both according to the manufacturer's recommendations and correcting the obtained values by 10.3%. Bland-Altman plots, Pearson's correlation coefficient, Lin's concordance correlation coefficient and multivariate models were used to investigate the difference in cfPWV. RESULTS cfPWV assessed in 118 patients (age 55 ± 12 years, 61% hypertensive patients, BMI 28.9 ± 4.4  kg/m2) with the Complior device was lower than that assessed with the SphygmoCor device, regardless of correcting the subtracted carotid-femoral distance (8.7 vs. 10.3  m/s and 9.3  m/s, respectively; P value < 0.001). The average difference was -1.59 ± 1.5 and -0.617 ± 1.39  m/s for corrected and uncorrected SphygmoCor values, respectively, SBP, BMI and female being the main determinants of the difference. Cardiovascular risk stratification changed in up to 40% of the study population, depending on the device and the arterial distance estimation. CONCLUSION The concordance between the Complior and the SphygmoCor device is poor when the anatomical artery length is controlled for and in the presence of cardiovascular risk factors, resulting in a difference in classification of cardiovascular risk.

Oscar Calaforra

Papers

Pulse pressure amplification and its determinants

Influence of obesity in central blood pressure.

Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease.

Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: A multicenter, randomized, double-blind study

Carotid-femoral pulse wave velocity assessment by two different methods: implications for risk assessment.