Search

Objective: Mean arterial pressure (MAP) is usually calculated by adding one-third of pulse pressure (PP) to DBP. This formula assumes that the average value of pulse waveform is constant in all individuals and coincides with 33.3% of PP amplitude (MAP = DBP + PP × 0.333). Other formulas were lately proposed to improve the MAP estimation, adding to DBP an established percentage of PP: MAP = DBP + PP × 0.40; MAP = DBP + PP × 0.412; MAP = DBP + PP × 0.333 + 5 mmHg., Methods: The current study evaluated the integral of brachial pulse waveform recorded by applanation tonometry in 1526 patients belonging to three distinct cohorts: normotensive or hypertensive elderly, hypertensive adults, and normotensive adults., Results: The percentage of PP to be added to DBP to obtain MAP was extremely variable among individuals, ranging from 23 to 58% (mean: 42.2 ± 5.5%), higher in women (42.9 ± 5.6%) than men (41.2 ± 5.1%, P < 0.001), lower in the elderly cohort (40.9 ± 5.3%) than in the general population cohort (42.8 ± 6.0%, P < 0.001) and in the hypertensive patients (42.4 ± 4.8%, P < 0.001). This percentage was significantly associated with DBP (β = 0.357, P < 0.001) and sex (β = 0.203, P < 0.001) and significantly increased after mental stress test in 19 healthy volunteers (from 39.9 ± 3.2 at baseline, to 43.0 ± 4.0, P < 0.0001). The average difference between MAP values estimated by formulas, compared with MAP assessed on the brachial tonometric curve, was (mean ± 1.96 × SD): -5.0 ± 6.7 mmHg when MAP = DBP + PP × 0333; -1.2 ± 6.1 mmHg when MAP = DBP + PP × 0.40; -0.6 ± 6.1 mmHg when MAP = DBP + PP × 0.412; -0.4 ± 6.7 mmHg when MAP = DBP + PP × 0.333 + 5., Conclusion: Due to high interindividual and intraindividual variability of pulse waveform, the estimation of MAP based on fixed formulas derived from SBP and DBP is unreliable. Conversely, a more accurate estimation of MAP should be based on the pulse waveform analysis.

Objective: Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype., Methods: A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations., Results: PWV and central pulse pressure were significantly higher in MFS patients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P < 0.0001], with a higher age-related increase of PWV in MFS (β 0.062 vs. 0.036). Pressure amplification was significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P < 0.0001]. Central pressure profile was altered even in MFS patients without aortic dilatation. Multiple linear regression models showed that PWV independently predicted aortic diameters at the sinuses of Valsalva (ß = 0.243, P = 0.002) and at the sinotubular junction (ß = 0.186, P = 0.048). PWV was higher in 'dominant negative' than 'haploinsufficient' fibrillin-1 mutations [7.37 (7.04-7.70) vs. 6.60 (5.97-7.23) m/s, P = 0.035], although this difference was not significant after adjustment., Conclusion: Aortic stiffness is increased in MFS, independently from fibrillin-1 genotype and is associated with diameters of ascending aorta. Alterations in central hemodynamics are present even when aortic diameter is within normal limits. Our findings suggest an accelerated arterial aging in MFS.

Objective: Aortic stiffness and central pressure measurements have become increasingly important for the overall estimation of cardiovascular risk. The aim of this study is to verify whether the presence of stenosis in the carotid arteries due to atherosclerotic plaques may induce a bias in the measurement of carotid-femoral pulse wave velocity (PWV) and in the analysis of central pulse waveform variables assessed by carotid tonometry., Methods: Eighty-four patients (age: 67.1 ± 12.4 years) undergoing screening for carotid atherosclerosis were enrolled, divided into three groups according to carotid ultrasound findings (NASCET criteria): 28 patients without significant stenosis, 30 patients with bilateral plaques, and 26 patients with right or left monolateral stenosis. PWV and other variables derived from the central pulse waveform analysis (central blood pressure, augmentation index and forward and backward waves) were measured at both right and left carotid arteries by a validated PulsePen tonometer. A repeatability study was performed in 28 young healthy patients (age: 25.4 ± 2.9 years)., Results: A high degree of correlation was found between bilateral measurements in all groups, and particularly in groups with monolateral carotid stenosis, with no significant difference attributable to lateralized stenosis. Right-left differences in asymmetric groups were 0.35 ± 5.12 mmHg (R = 0.960) for central blood pressure, -2.12 ± 7.39% (R = 0.743) for augmentation index, 0.64 ± 1.56 m/s (R = 0.947) for PWV, 0.08 ± 8.48 mmHg for forward wave (R = 0.742) and 0.35 ± 2.35 mmHg for backward wave (R = 0.907)., Conclusion: Measurement of PWV and of variables derived from the central pulse waveform analysis by carotid tonometry is not biased by the presence of local atherosclerotic plaques.

Objectives: The mechanisms underlying the increased cardiovascular risk after menopause are poorly understood. Estrogens modulate the cardiac renin-angiotensin system (RAS) and influence cardiac adaptation to afterload. To investigate whether the loss of the natural inhibition of the RAS by estrogen may be linked to an increase of cardiac apoptosis, we studied 17β-estradiol (E2) and/or angiotensin-converting enzyme (ACE) inhibitor treatment effects on cardiomyocyte survival in ovariectomized spontaneously hypertensive rats (SHRs)., Methods: Five groups of female SHRs were evaluated for 8 weeks. One group served as nonovariectomized control; the other four groups underwent bilateral ovariectomy and were randomized to receive 60-day-release pellets containing placebo or 0.5 mg of E2, the ACE inhibitor ramipril at the dosage of 2.5 mg/kg per day, or the combination of the two treatments., Results: Ovariectomy increased cardiomyocyte apoptosis and induced proapoptotic changes of Bcl-2 and Bax genes and proteins. These modifications were associated with an upregulation of ACE and angiotensin II type 1 (AT1) receptor genes. Ramipril was as effective as E2 in preventing cardiac apoptosis and in restoring cardiac brain natriuretic peptide in association with reduced cardiac ACE and AT1 receptor gene expression. In contrast to the ramipril treatment, the favorable effect of E2 on cardiac apoptosis occurred independently from changes in SBP. No synergistic effect was observed when the two treatments were combined., Conclusion: These data show that ovariectomy stimulates myocardium apoptosis by a mechanism involving Bax and Bcl-2 genes. The antiapoptotic effect of E2 and ACE inhibitor treatment was linked to a downregulation of cardiac RAS.

Objective: To gain insight into the regulation of cardiac apoptosis we studied the dose-response and time-course effects of angiotensin II (Ang II) infusion on ventricular cardiomyocyte apoptosis and on the expression of Bax and Bcl-2 genes and proteins., Study Design and Methods: In the dose-response study, Ang II was infused subcutaneously at doses of 100, 200, 400, 800 and 1200 ng/kg per min for 14 days. In the time-course study, rats infused with Ang II at doses of 200 and 400 ng/kg per min were followed for 7 and 14 days. The cardiomyocyte apoptotic density was assessed by DNA end labelling (terminal deoxynucleotide nick-end labelling; TUNEL). Gene and protein expression of Bcl-2 and Bax were evaluated by reverse transcriptase-polymerase chain reaction and by Western blots., Results: Systolic blood pressure and left ventricular mass were increased in a dose-dependent manner in Ang II-infused rats. A statistically significant increase in the rate of cardiac apoptosis and pro-apoptotic changes of Bcl-2 and Bax gene and protein expression was observed when high doses of Ang II (800-1200 ng/kg per min) were infused. A positive correlation of apoptotic density with Bax and a negative correlation with Bcl-2 and Bcl-2/Bax ratio were found. Cardiac apoptosis was greatly influenced by the timing of Ang II infusion. Losartan-treated Ang II-infused rats exhibited normalized systolic blood pressure, left ventricular weight, apoptosis, and Bax and Bcl-2 levels., Conclusions: Our results are consistent with the pathophysiological role of Ang II in induction of cardiac apoptosis, and explain the cardioprotective effect of Ang II receptor antagonists.

Objective: Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats., Design and Methods: Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated., Results: The blood pressure reduction was equal in rats receiving either SPI or HRH. The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis., Conclusions: The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis.

We have compared the cardiac performance of four groups of rats: normotensive control rats (NCR) and spontaneously hypertensive rats (SHR) not drinking alcohol, and NCR and SHR drinking 20% alcohol (NCR-A and SHR-A, respectively), over a period of 6-9 months.