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It is still debated whether arterial elasticity provides prognostic information for cardiovascular risk beyond blood pressure measurements in a healthy population. To investigate the association between arterial elasticity obtained by radial artery pulse wave analysis and risk for cardiovascular diseases (CVD) in men and women. In 2002-2005, 2362 individuals (men=1186, 50.2%) not taking antihypertensive medication were included. C2 (small artery elasticity) was measured using the HDI/Pulse Wave CR2000. Data on acute myocardial infarction or stroke, fatal or non-fatal, was obtained between 2002-2019. Cox- regression was used to investigate associations between C2 and future CVD, adjusting for confounding factors such as age, sex, systolic blood pressure, heart rate, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LDL- cholesterol, CRP (C-Reactive Protein), alcohol consumption, smoking and physical activity. At baseline, the mean age of 46 ± 10.6 years and over the follow-up period, we observed 108 events 70 events in men [event rate: 5.9%], 38 in women [event rate: 3.2%]. In the fully adjusted model, and for each quartile decrease in C2, there was a significant increase in the risk for incident CVD by 36%. (HR = 1.36, 95% CI: 1.01-1.82, p = 0.041). The results were accentuated for all men (HR = 1.74, 95% CI: 1.21-2.50, p = 0.003) and women over the age of 50 years (HR = 1.70, 95% CI: 0.69-4.20). We showed a strong and independent association between C2 and CVD in men. In women after menopause, similar tendencies and effect sizes were observed., (© 2023. The Author(s).)

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Pharmacotherapy to protect the arteries may be appropriate for individuals with high-normal blood pressure who are at risk for future cardiovascular disease (CVD). Nebivolol (NEB) in contrast to atenolol (ATE) may have a beneficial effect on endothelial function and may be more effective than ATE in preventing CVD. Sixty subjects with preHTN or borderline BP and abnormal small artery elasticity (SAE) underwent evaluation with 10 tests, including large and small artery elasticity, resting and treadmill exercise BP, carotid intimal-media thickness, retinal vascular photography, micro-albuminuria, electrocardiography, echocardiography, and plasma B-type natriuretic peptide level. Each test scored as normal (0), borderline (1), or abnormal (2), and the total disease score (DS) was calculated by adding the test scores. Subjects were randomized double-blind to placebo (PLAC, n = 22), NEB 5/10 mg/day (n = 20), or ATE 25/50 mg/day (n = 18) once daily for 9 months. After 9 months, in the group receiving NEB the mean (standard deviation) DS decreased from baseline 4.3 (2.6) to 2.8 (2.4) (P < 0.007), with ATE from 5.4 (2.5) to 3.5 (1.9) (P = 0.0006), and with PLAC from 5.2 (3.0) to 4.5 (2.6) (P = 0.18). SAE increased in the NEB group from 6.0 (2.2) to 8.4 (3.4) ml/mmHg × 100 (P = 0.0001), whereas there was no significant change in the ATE and PLAC groups. Thus, nebivolol improves small artery function more than atenolol in asymptomatic subjects with preHTN or borderline BP, despite their similar BP-lowering effect.

Antihypertensive therapy is aimed at improving vascular and cardiac health, as well as lowering blood pressure (BP). The benefit of such drugs in untreated patients with borderline BP has not been demonstrated. Subjects with BPs ≥130 mm Hg systolic or ≥85 mm Hg diastolic and at least one additional risk factor were randomly assigned to treatment with carvedilol, lisinopril, their combination or placebo. Cardiovascular health was assessed by a disease score (DS), which combines the following tests of cardiovascular function and structure: resting BP, large- and small-artery elasticity (SAE), BP response to exercise, retinal vasculature analysis, electrocardiogram, carotid intima-medial thickness, left ventricular mass, microalbuminuria and N-terminal pro B-type natriuretic peptide. DS was assessed at baseline, after 3 and 9 months of therapy and 1 month after discontinuation of therapy. All active treatment groups displayed a sustained reduction in BP during 9 months of treatment, with the greatest reduction in the cardvedilol+lisinopril group. DS and SAE improved in all the treatment groups but the changes were of borderline significance and exhibited no evidence for progressive improvement from 3 months (functional) to 9 months (structural). All changes were reversed within 1 month after discontinuation of therapy. We conclude that 9 months of treatment with carvedilol, lisinopril or their combination produce a sustained and well-tolerated functional improvement but not a structural improvement, perhaps because of a lack of the nitric oxide-enhancing effects of other agents that inhibit structural changes in the vasculature.

Efficacy and safety of the direct renin inhibitor aliskiren was compared with ramipril for treatment of essential systolic hypertension in elderly patients. A 36-week, randomized, double-blind, parallel-group, active-controlled, optional-titration study was performed in 901 patients (aliskiren, n=457; ramipril, n=444) > or =65 years of age with systolic blood pressure (SBP) > or =140 mm Hg. Aliskiren 150-300 mg per day or ramipril 5-10 mg per day for was administered for 12 weeks with optional add-on therapy of hydrochlorothiazide (12.5-25 mg per day) at week 12 and amlodipine (5-10 mg per day) at week 22. The primary end point was non-inferiority of aliskiren vs ramipril monotherapy for change from baseline in mean sitting SBP (msSBP) at week 12. Decreases from baseline msSBP and mean sitting diastolic BP with aliskiren monotherapy (-14.0 and -5.1 mm Hg, respectively) were non-inferior (P<0.001 for both values) and superior to ramipril monotherapy (-11.6, -3.6 mm Hg; P=0.02, P<0.01, respectively). More patients achieved BP control with aliskiren (42%) than ramipril (33%; P<0.01). At week 36, fewer patients receiving aliskiren-based therapy required add-on treatment with hydrochlorothiazide or amlodipine (P=0.01 and 0.048, respectively). Tolerability was similar, but more patients receiving ramipril reported cough (P<0.001). In elderly patients with systolic hypertension, aliskiren proved to be more effective and better overall anti-hypertensive therapy compared to ramipril.

Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. Brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) are considered as novel biomarkers that are useful in the prediction of early cardiovascular risk. We studied the relationship between carotid artery stiffness index beta and the cardiovascular biomarkers BNP and hs-CRP in 55 consecutive subjects. Carotid artery stiffness was assessed using the stiffness index beta derived from brachial artery blood pressure measurement and carotid ultrasonography. Venous blood samples were obtained for BNP and hs-CRP. Pearson's correlation coefficient suggested a strong bivariate relationship between carotid stiffness index beta and age (r=0.56, P<0.0001), BNP (r=0.45, P<0.004) and hs-CRP (r=0.26, P=0.06), respectively. On multiple regression analysis, significant correlations were found between carotid stiffness index beta and age (P=0.004), BNP (P=0.027) and hs-CRP (P=0.029). These findings suggest that there is a relationship between intra-cardiac pressures (measured by BNP), vascular inflammation (measured by hs-CRP) and vascular stiffness. Cardiovascular biomarkers are thus associated with functional parameters of the vascular tree.

Plasma concentration of high sensitive C-reactive protein (hsCRP) is used as a marker for inflammatory states and is directly correlated with the risk for coronary heart disease. Evidence concerning the role of inflammation in atheroma formation has been derived from several models of atherosclerosis. Inflammation should exert its adverse vascular effects by structural changes in the artery wall and consequently alterations in arterial elasticity, which could be detected already in asymptomatic early vascular disease. We hypothesized that CRP is related to large artery elasticity, but not to small artery elasticity in early vascular disease. Therefore, we examined the association between arterial stiffness of large and small arteries and inflammation in an asymptomatic population referred for primary prevention cardiovascular screening. Studies were performed in 391 subjects (age 21-82 years; 254 men, 137 women) who underwent screening at the Cardiovascular Disease Prevention Center. Large artery (C1) and small artery (C2) elasticity indices were obtained by the CVProfiler 2000 (HDI, Eagan, MN, USA). After overnight fasting, venous samples were taken for measurement of hsCRP, lipids, glucose. There was a significant inverse correlation between hsCRP (0.29 +/- 0.40 mg/dl) and C1 (16.7 +/- 5.8 ml/mmHg), r = -0.133, P = 0.01; there was no significant correlation between hsCRP and C2 (6.6 +/- 3.2 ml/mmHg). C2, but not hsCRP, was inversely correlated with age, abnormal lipids and glucose, whereas C1, but not hsCRP, was inversely correlated with age and systolic blood pressure (SBP). In multiple regression analysis, the relationship between hsCRP and C1 was not affected by age, body mass index, SBP, serum glucose or lipids. In conclusion, these findings support the hypothesis that hsCRP, a marker for acute and low-grade inflammation, is associated with large artery but not with small artery elasticity in asymptomatic individuals undergoing primary prevention cardiovascular screening.

Structural and functional abnormalities may occur at the left ventricle and in different large arteries in essential hypertension. Noninvasive high resolution pulsed doppler echo-tracking technique allows calculation of regional arterial wall properties, which might be determined by either hemodynamic or non-hemodynamic factors. Therefore we aimed to study regional arterial wall properties in three different vascular territories and examined whether hemodynamic and non-hemodynamic parameters were significantly associated to a specific vascular territory. In 30 patients (mean age 47 +/- 2 years) with newly diagnosed and untreated essential arterial hypertension, arterial wall properties were determined at the carotid (common, external and internal), femoral, and brachial artery using a noninvasive ultrasound wall movement detector system. The study parameters were arterial diameter, relative diameter change, arterial distensibility (DC) and cross-sectional compliance (CC) coefficient. On the day of the experiments office blood pressure (BP) was measured as well as an ambulatory 24 h BP profile performed on an outpatient basis. Blood samples were taken on the day of the vascular examination for the determination of plasma renin activity (PRA), aldosterone, intact (1-84) parathyroid hormone (PTH), insulin and plasma noradrenaline and adrenaline. Among the studied vascular territories, only DC and CC of the common carotid artery were significantly (P < 0.01) correlated with office and ambulatory systolic BP. Intact PTH was significantly correlated with the diameter (r = 0.61, P = 0.005) and DC (r = -0.53, P = 0.01) of the internal carotid artery. Noradrenaline was inversely correlated with DC of the femoral artery (r = - 0.55, P < 0.01). All correlations remained significant after adjustment for age and body mass index as confounding variables. In conclusion, in mild to moderate arterial essential hypertension there is a heterogeneity of vascular wall properties and their relationship to BP and humoral factors between brachial, femoral and carotid (common, external and internal) arteries. Our findings might renew interest in the old concept of the 'circulatory paradox'.