de Simone G

Age-related changes in total arterial capacitance from birth to maturity in a normotensive population

We evaluated the effect of body growth and aging on the ratio of echocardiographic (Teichholz) stroke volume to pulse pressure (SV/PP ratio) in 373 normal-weight, normotensive children to adolescents (1 day to 17 years old; 166 girls, 87 nonwhite) and 393 normal adults (17 to 85 years old; 164 women, 112 nonwhite). Stroke volume increased with age in children (r = .64, P < .0001) and was stable in adults; pulse pressure decreased slightly with age in children (r = -.10, P = .06) and increased in adults (r = .29, P < .0001). As a consequence, SV/PP ratio increased with age in children (r = .51, P < .0001) and decreased in adults (r = -.18, P = .0004). To control for changes in body size that influence the size of the arterial tree, we used ANCOVA to adjust SV/PP for body size. Body size-adjusted SV/PP ratio was no longer related to age in children, whereas the negative relation with aging in adults remained statistically significant (r = -.19, P < .0002). Heart rate was negatively related to SV/PP ratio in both children and adolescents and adults, but this relation did not influence the relation with age. In multivariate analysis, high SV/PP ratio was predicted by greater height (P < .002) and weight (P < .04) and nonwhite race (P < .001) in children and adolescents and by younger age (P < .0001), greater weight (P < .0001), and low heart rate (P < .001) in adults. Sex did not enter the regression models. Thus, (1) SV/PP ratio is a measure of increasing capacity of the arterial tree during growth, whereas it depends on arterial compliance during adulthood through old age; (2) arterial compliance decreases progressively with aging; (3) the apparent difference between males and females might be due to their different body sizes.

Cardiovascular risk in relation to a new classification of hypertensive left ventricular geometric abnormalities.

Objectives: In 2010, the Dallas Heart Study proposed an upgrade of the left ventricular geometric classification proposed in 1991, by using left ventricular mass combined with end diastolic volumes, and introducing the new categories of dilated left ventricular hypertrophy (LVH). We adopted the new method to test the prognostic impact of the left ventricular geometric patterns from the new classification. Methods: We evaluated baseline anthropometric, laboratory and echocardiographic parameters of 8848 hypertensive patients from the Campania Salute Network (53 ± 12 years, 56% male), free of prevalent cardiovascular disease, valve disease and with ejection fraction ≥50%. Cut points for left ventricular mass index, relative wall thickness and left ventricular end-diastolic dimension (cm/m) were derived from our historical normal reference population. Composite cardiovascular end-points were cardiac death, fatal and nonfatal myocardial infarction and stroke. Results: Independent of confounders, eccentric dilated LVH, concentric nondilated LVH and concentric dilated LVH were associated with higher cardiovascular risk (hazard ratios between 2 and 9, all P < 0.01), mostly depending on the magnitude of LVM index. A volume load was present especially in dilated forms of LVH, the extent of which was important in the determination of harmful types of left ventricular geometry. Conclusion: Consideration of left ventricular dilatation in the evaluation of risk related to hypertensive left ventricular geometry reveals the importance of the extent of the volume load coexisting with the typical hypertensive pressure overload. At a given normal ejection fraction, the balance between the two hemodynamic components influences the shape of left ventricular geometric adaptation, the amount of left ventricular mass and the impact on prognosis.

Relation of left ventricular longitudinal and circumferential shortening to ejection fraction in the presence or in the absence of mild hypertension.

Objectives To study left ventricular longitudinal shortening in arterial hypertension and the relative contribution of longitudinal and circumferential fiber shortening to ventricular ejection. Methods Two-dimensional and M-mode echocardiograms were obtained for 50 normotensive subjects (aged 49 ± 12 years) and 50 never-treated mild hypertensive patients (aged 49 ± 11 years), to measure the minor-axis endocardial and midwall shortening, long-axis shortening and ejection fraction. Results The midwall shortening was lower in hypertensive than it was in normotensive subjects (P < 0.001) and was related inversely to the circumferential wall stress for both groups (P < 0.04 and 0.0001, respectively). The long-axis shortening in hypertensive patients (22.2 ± 4.2%) and in normotensives (23.6 ± 5.4%) was not statistically different, and was not related either to the meridional or to the circumferential wall stress. The ejection fraction was also similar for the two groups (68.2 ± 6.3 versus 68.6 ± 5.6%). Both for normotensive and for hypertensive subjects, the ejection fraction was influenced mainly by the midwall shortening (61 and 40% of the variance for normal and hypertensive individuals, respectively), with a minor contribution from the long-axis shortening, which was 7% for normotensive subjects and 18% for hypertensive patients, a statistically significant difference (P < 0.001). The combined effect of midwall and longitudinal shortenings on the ejection fraction was regulated by the relative wall thickness, and was maximal for hypertensive patients with an ejection fraction greater than that predicted by the midwall shortening Conclusions Left ventricular ejection is produced principally by circumferential shortening and is related independently to the relative wall thickness. In the presence of arterial hypertension and an altered cardiac load, longitudinal shortening becomes an important mechanism by which to augment ejection, thereby offsetting the reduction in midwall shortening.

Classes of antihypertensive medications and blood pressure control in relation to metabolic risk factors.

Objective Metabolic syndrome (MetS) is associated with uncontrolled blood pressure (BP), despite use of aggressive therapy. This study was performed to assess whether the use of different classes of antihypertensive drugs might influence this association. Methods We evaluated risk of uncontrolled BP (BP ≥ 140/90 mmHg under antihypertensive treatment) at the time of the last available visit, after a mean follow-up of 5 years in 4612 hypertensive patients without prevalent cardiovascular disease (43% women, 53 ± 11 years) from the Campania Salute Network. Results At the time of the first visit, prevalence of MetS was associated with 43% increased risk of follow-up uncontrolled BP, independent of significant confounders and without a significant impact of specific classes of antihypertensive medications. At the time of the last available visit, patients with MetS had more often uncontrolled BP, despite more aggressive treatment. After adjusting for demographics, risk factors and number of antihypertensive medications, risk of uncontrolled BP was reduced with increased prescription of diuretics [DRTs; odds ratio (OR) 0.73, 95% confidence interval (CI) 0.62–0.86], renin–angiotensin system blockers [RAS-blockers (Angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers); OR 0.77, 95% CI 0.66–0.91] and statins (OR 0.79, 95% 0.68–0.92, all P < 0.05), without significant impact of the other classes of medications. Conclusion Despite the use of increased number of medications, hypertensive patients with MetS are at higher risk of uncontrolled BP. Among classes of antihypertensive medications, increased prescriptions of DRTs, RAS-blockers and also statins decrease the probability of poor BP control.

Initial left-ventricular mass predicts probability of uncontrolled blood pressure in arterial hypertension.

Background Left-ventricular hypertrophy (LVH) is a marker of organ damage in hypertension and helps stratifying cardiovascular risk. Initial left-ventricular mass (LVM) is also a predictor of progression to hypertension, independently of initial blood pressure (BP) and other confounders. Objectives To evaluate whether baseline LVM can influence BP control in treated hypertension. Methods We evaluated risk of uncontrolled BP (>140 or 90 mmHg under at least two medications), in relation to initial LVM in 4693 hypertensive outpatients (mean age 53 ± 11years, 43% women, 5% diabetic), without prevalent cardiovascular disease, from the Campania Salute Network. Results Uncontrolled BP was found in 2240 patients (48%). Participants with initial LVH were more often men, older, diabetic, had higher initial BP, fasting glucose, uric acid and triglycerides, and lower heart rate (HR), high-density lipoprotein-cholesterol and glomerular filtration rate than those without LVH (all P < 0.05). Of 1440 patients with initial LVH, 803 (56%) were uncontrolled at follow-up compared to 44% without LVH (P < 0.0001). In multivariate analyses, odds of uncontrolled BP increased with higher baseline systolic BP [odds ratio (OR) = 1.13 × 5 mmHg, 95% confidence interval (CI) 1.10–1.15], HR (OR = 1.04 × 5 beats/min, 95% CI 1.01–1.07), BMI (OR = 1.03 × kg/m2, 95% CI 1.01–1.04), LVM index (OR = 1.05 × 5 g/m2.7, 95% CI 1.01–1.10) and prevalence of diabetes (OR = 5.22, 95% CI 3.52–7.76; all P < 0.05) independently of age, sex, metabolic parameters and number of antihypertensive meds (P > 0.1). Among medication classes, only angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were associated with lower risk of uncontrolled BP (OR = 0.83, 95% CI 0.71–0.96; P = 0.01), independently of covariates. Conclusion In a population of treated hypertensive patients, initial LVM is a significant predictor of uncontrolled BP, independently of major risk factors and antihypertensive therapy.

Clinical impact of various geometric models for calculation of echocardiographic left ventricular mass

Background M-mode echocardiographic left ventricular mass calculated using a thick-wall prolate ellipsoidal model is widely used in clinical and epidemiologic studies. Doubts regarding the ability of this approach to obtain a precise estimate of left ventricular weight across a wide range of values have recently been raised and an alternate thin-wall ellipsoidal model has been proposed to gain greater precision. Objective To compare thin-wall and thick-wall (American Society of Echocardiography and Penn convention) models for calculation of left ventricular mass. Design Validation, cross-sectional, and longitudinal studies. Participants Necropsy data and living cohorts from Naples, New York City, and Umbria region of Italy (PIUMA registry). Results The average thin-wall left ventricular mass was slightly greater than the necropsy left ventricular weight (mean 225 versus 220 g), whereas no difference was detected using regression-adjusted thick-wall methods. Use of the thin-walled model slightly overestimated left ventricular mass relative to both thick-wall models at the lowest left ventricular mass while slightly underestimating the highest values. Comparison of Cox proportional hazard models in two longitudinal studies demonstrated that there was a substantial equivalence among methods, with a marginally better performance of thick-wall models for cardiovascular risk stratification (P < 0.05 in one study). Conclusions Although it is imperfect, because it is based on simplifying geometric assumptions, computation of left ventricular mass on the basis of M-mode echocardiographic left ventricular dimensions using thick-wall prolate-ellipsoidal models is valuable for identification of left ventricular hypertrophy and for cardiovascular risk stratification of patients with essential hypertension. Calculation of left ventricular mass by use of a thin-wall prolate-ellipsoidal geometry does not yield appreciably different results than those which are obtained by use of thick-wall models.

Development of new atherosclerotic plaque in hypertensive patients: an observational registry study from the Campania-Salute network.

Background and purpose: Carotid atherosclerotic plaques (CAPs) can develop despite appropriate antihypertensive therapy. In this observational study, we assessed characteristics associated with risk of incident CAP in a large hypertensive registry. Methods: We evaluated 2143 hypertensive patients without evidence of CAP. Incident CAP was censored at the time of the first ultrasound control in which CAP was detected. CAP was defined according to European Society of Hypertension/European Society of Cardiology guidelines. Results: At a median follow-up period of 56.6 months, about one-third of patients (32%; N = 688) exhibited new CAP. Those patients were older, more frequently smokers, diabetic, more often with metabolic syndrome, chronic kidney disease (CKD), longer hypertension history, higher baseline SBP, pulse pressure (PP), fasting glucose, total cholesterol and triglycerides, greater left ventricular mass index, higher PP/stroke index ratio and carotid intima–media thickness (IMT; all P < 0.05). In-treatment BP control was similar in both groups. In multivariable Cox regression, CAP was predicted by older age, diabetes, smoking habit, CKD and higher value of initial IMT (all P < 0.02), independently of BP control during follow-up, antihypertensive therapy and other confounders. Conclusion: In this registry of treated hypertensive patients, after adjusting for age and other confounders, risk of incident CAP did not depend on BP control and type of antihypertensive therapy, whereas it was independently related to the magnitude of initial IMT, independently of significant effect of prevalent diabetes and smoking habit. These findings suggest that antihypertensive treatment strategy to stop progression of cardiovascular disease might be difficult to achieve, once target organ damage is established.

Serial echocardiographic assessment of left ventricular mass: how blinded should readers be?

Objectives In addition to the interest of mixing the sequence of echo-exam in a central blinded review, we studied the effect that might result from group-analysis of all echocardiograms simultaneously for each patient, with their sequence kept blind. A priori, this method of reading has the potential of decreasing measurement variability. Methods We included 630 echocardiograms from 210 hypertensive patients participating in a randomized clinical trial comparing two antihypertensive agents for regression of left ventricular (LV) hypertrophy. Three echocardiograms per patient [selection (4 weeks before; W−4), at inclusion (week 0; W0), and the end of treatment (week 52; W52)], were read twice, according to two methods, blind to centre, patient numbers and sequence of visits: (1) examination of individual serial echocardiograms, (2) examination of all-patient mixed echocardiograms. The first method was expected to increase the power of treatment comparison by reducing variability of measurements of left ventricular mass (LVM). Results Pooling echocardiograms of all patients reduces variability of LVM change under treatment: absolute LVM (W52 − W0) standard deviation was reduced by 22%. Nevertheless, despite a good between-methods agreement for LVM values at each visit (intra-class coefficient of correlation from 0.88 to 0.92), LVM change under treatment was reduced even more, by 41%. Thus, the slight decrease of variability induced by gathering the echocardiograms is associated with an even greater reduction of LVM change. Conclusions According to these findings, the ‘full-blind’ methodology for a central blinded review in clinical trials appears to produce the maximum power of the study with the lowest sample size.

Aortic root dimension and arterial stiffness in arterial hypertension: the Campania Salute Network.

Objectives: The relation between aortic root dimension (ARD) and measures of arterial stiffness is uncertain. Accordingly, we studied the relation between ARD and an estimate of arterial stiffness in 12 392 hypertensive patients (age 53 ± 12 years, 43% women) free of prevalent cardiovascular disease and with ejection fraction at least 50%, from the Campania Salute Network Registry. Methods: Echocardiographic ARD was measured and compared with the value predicted by age, sex and height by using a z-score. Arterial stiffness was assessed by the pulse pressure/stroke index. The highest population tertile of pulse pressure/stroke index was considered ‘high arterial stiffness’. Results: High arterial stiffness was more common in women than in men (P < 0.001) and associated with older age, diabetes, longer duration of hypertension and less frequent smoking habit (all P less than 0.01). Patients with high arterial stiffness had smaller ARD, higher carotid intima–media thickness and plasma cholesterol, and lower BMI and glomerular filtration rate (all P less than 0.01). In multivariable logistic analysis, high arterial stiffness was associated with both lower ARD z-score [OR 0.83 (95% confidence interval 0.79–0.88)] and higher carotid intima–media thickness [OR 1.36 (95% confidence interval 1.26–1.47); both P less than 0.0001], independent of significant associations with age, female sex, body size, DBP, heart rate, duration of hypertension, diabetes and smoking habit. Conclusion: Small ARD, together with atherosclerotic modifications of conduit arteries, is associated with increased 2-element Windkessel model of arterial stiffness in hypertension, independently of the significant effect of confounders.

Impact of pulse pressure on left ventricular global longitudinal strain in normotensive and newly diagnosed, untreated hypertensive patients.

Objectives: Little is known about the impact of pulse pressure on left ventricular systolic function. The aim of our study was to evaluate whether high pulse pressure is associated with subclinical left ventricular systolic dysfunction. Methods: The study population included 143 participants (68 newly diagnosed, never-treated hypertensive, and 75 normotensive individuals) evaluated by echo-Doppler, including determination of global longitudinal strain (GLS) by speckle tracking. According to pulse pressure tertiles, participants were divided in two groups: the first group merging the first and second pulse pressure tertiles (n = 93, pulse pressure <55 mmHg) and the second group including the highest pulse pressure tertile (HPPT; n = 50, pulse pressure ≥55 mmHg). Results: The two groups were comparable for sex, BMI, and heart rate, whereas age was higher in individuals with the HPPT (P < 0.0001). Left ventricular mass index was significantly higher in individuals with the HPPT (P < 0.01), with no significant difference in relative wall thickness. Among several indices of left ventricular systolic function, only GLS was lower in individuals with the HPPT (P < 0.001). Transmitral E/A ratio (P = 0.006) was lower and E/e’ ratio higher (P < 0.001) in the HPPT group. By a multilinear regression analysis, HPPT (P < 0.020) and overweight (P = 0.025) were independent correlates of low GLS. Replacing HPPT with the highest systolic blood pressure tertile, GLS was independently associated with BMI (P = 0.040), but not with the highest systolic blood pressure tertile (P = 0.069). Conclusion: Elevated pulse pressure negatively influences left ventricular longitudinal mechanics in a mixed population of normotensive and untreated hypertensive individuals.