DIFFERENTE RELAZIONE TRA VALORI PRESSORI E MASSA VENTRICOLARE SX NEI DUE SESSI IN PAZIENTI IPERTESI.

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1 DIFFERENTE RELAZIONE TRA VALORI PRESSORI E MASSA VENTRICOLARE SX NEI DUE SESSI IN PAZIENTI IPERTESI. Franco Cipollini, Carlo Porta, Enrica Arcangeli, Carla Breschi, & Giuseppe Seghieri Azienda USL 3, Ambulatorio per l Ipertensione Arteriosa, Spedali Riuniti, Pistoia

2 Introduction and Aims of the Study There are evidences to support the hypothesis that women myocardial mass is more susceptible than the male heart to hypertrophy in response to blood pressure load in either humans or in animal models. Furthermore the prediction of cardiovascular morbidity and mortality exerted by left ventricular hypertrophy (LVH) in patients with hypertension seems to be more pronounced in women than in men. The present study was therefore undertaken to investigate the different response between blood pressure, recorded by 24-hour monitoring, and LVM, measured by echocardiographic method, in a population of hypertensive outpatients.

3 Subjects & Methods (1) Population under study The population under study comprised all patients who were consecutively referred by their general practitioners to the outpatient clinic for arterial hypertension of our Hospital (Spedali Riuniti, Pistoia), in order to confirm borderline or white coat hypertension or to modify treatment, where the response to the antihypertensive therapy prescribed at home was judged inadequate. Home therapy was constituted by diuretics, ACE inhibitors, Ca channel blockers and α 1 -blockers alone or in various combination. No difference was present in type of therapy between genders. Diagnosis of diabetes was done according to the anamnestic recall by patients or by measuring fasting plasma glucose (> 7mmol/l).

4 Subjects & Methods (2) Blood pressure was recorded in all patients by a same physician, with a mercury sphygmomanometer, in the sitting position after 10 min rest. The mean of 3 measurements was taken for analysis. Twenty-four hour ambulatory BP was recorded by using an oscillometric device (model SpaceLabs 90207) that was set to take BP readings every 15 min during the day and every 30min during the night. Left ventricular mass (LVM) was measured through echocardiographic method using Devereux s formula [LVM (g)=0.80x(1.04x(d+p+s) 3 -D 3 ) +0.6] and indexed by height 2.7. Comparison between means was performed by using Student s t test. χ 2 test was used to evaluate the significance of differences in proportions. Relations were assessed by Pearson s r correlations coefficients. Multivariate regression analysis model was used to evaluate multiple r and percentage of explained variance of the dependent variablesl. Relative risks, defined as odds ratio, were calculated by using a multiple logistic analysis model. All values are expressed as mean ± SD. The statistical tests were performed by using SAS software for Windows, version 8.2 (SAS Institute Inc., Cary, NC, USA).

5 Results (1) Table 1, shows that women were significantly older, while there was no difference between the sexes in body mass index (BMI) or prevalence of obesity. Twenty-four-hour systolic BP was slightly higher and 24-h diastolic BP significantly lower in women, since, consequently, pulse BP was markedly higher in these latter. Prevalence of hypertension expressed as mean systolic 24-hour BP>125mmHg and/or 24-hour diastolic BP>80mmHg, as well as of diabetes, and previous drug treatment were similar in both genders The left ventricular end-diastolic septal thickness, the posterior wall thickness, as well as the value of not indexed LVM, all measured by echocardiographic method, were significantly higher in men, while after correction for body surface or for height 2.7 LVM values were all together each other not different (Table 2). Left ventricular hypertrophy, present in the 22.5% of males and in 36.4% of females with a near significant preponderance among these latter (p=0.06), was eccentric in over the 70% of cases in both sexes (Table 2). According to the univariate analysis, LVM, indexed by height 2.7 was significantly related to age and to mean 24-hour systolic and pulse BP, while 24-hour diastolic BP was weakly inversely related with LVM only in the female group (r=-0.28; p=0.02). Correlation coefficients between 24-hour pulse pressure and LVM were higher in women than in men (Table 3). These relations remained significant, even after adjusting for possible confounders, as suggested by two separate multiple regression models: the first, which included both systolic and diastolic 24- hour BP into the set of independent covariates and the second which included the 24-hour pulse BP (Table 4).

6 Results (2) Percentage of LVM variance explained by BP values, as expressed by the multiple regression analyses, was on average higher among women than among men (about 55% vs. 45%), and once again 24-hour pulse BP was about sevenfold more important in predicting LVM variance in women than in men (40.77% vs. 6.19%) (Fig. 1). The percent increase in the relative risk of developing LVH (left ventricular mass 47 g/m 2.7 in women and 50 g/m 2.7 in men), expressed by odds-ratios adjusted for main confounders, and estimated for every 1mmHg increase, was ~2.7 times higher in women than in men, either considering the mean 24-hour systolic BP (21.4% vs 8.2%) or the 24-hour mean pulse BP (24.4% vs. 9%) (Table 5). Relative risk of developing LVH due to the increase in 24-hour diastolic blood pressure values was similar in men and in women (~8-10% for every 1mmHg increase), even considering that the odds-ratio value did not reach the full significance in women (10.8; 95%CI: ; Table 5). Non dipping status was related to a significantly higher relative risk of having LVH in women (Odds ratio: 7.88; 95% CI: ) after adjusting for age, diabetes, BMI and therapy, while it wasn t in men (Odds ratio: 2.47; 95% CI: ). All these differences were even more evident including only the hypertensive patients.

7 Conclusions 1. Pulse pressure was more elevated in women, as compared to men, due to a lower diastolic BP in the female gender, 2. LVM values, corrected for height 2.7 were not different in both genders even if left ventricular hypertrophy, eccentric in over the 70% of cases, showed a near significant preponderance among females, 3. LVM was significantly related to age and to mean 24-hour systolic and pulse BP, while 24-hour diastolic BP was weakly inversely related with LVM only in the female group, even after adjusting for possible confounders, 4. LVM variance explained by BP values, was on average higher among women than among men, and, once again, 24-hour pulse BP was about sevenfold more important in predicting LVM variance in women than in men, 5. The relative risk of developing LVH adjusted for main confounders, and estimated for every 1mmHg increase, was ~3 times higher in women than in men, either considering the mean 24-hour systolic and pulse BP, 6. Similarly non dipping status was related to a significant higher relative risk of having LVH in women while it wasn t in men.

8 Women (n=69) Men (n=80) Age (yrs) 51.9± ± Height (cm) 161± ± Weight (Kg) 66.8± ± Body surface area (m 2 ) 1.70± ± BMI (Kg/m 2 ) 25.8± ±3.2 NS 24-h mean systolic BP (mm Hg) 132± ±12.4 NS Office systolic blood pressure (mm Hg) 153.3± ± h mean diastolic BP (mm Hg) 79.4± ± Office diastolic blood pressure (mm Hg) 90.2± ±9.5 NS 24-h mean pulse pressure (mm Hg) 52.3± ± Office pulse pressure (mm Hg) 63± ± Heart rate (beats/min) 72±14 68±13 NS Therapy (%) NS Obesity (%) NS Diabetes (%) 12 8 NS Hypertension (%) NS Table 1 Main characteristics of the study population according to gender P

9 Women (n=69) Men (n=80) Interventricular end-diastolic septal thickness (cm) 1.08± ±0.8 NS Left ventricular end-diastolic diameter (cm) 4.74± ± Posterior wall end-diastolic thickness (cm) 1.08±0.81 1± Relative wall thickness (cm) 0.40± ±0.05 NS Left ventricular mass (g) 160±44 197± Left ventricular mass/body surface area (g/m 2 ) 94.2± ±23.6 NS Left ventricular mass/height 2.7 (g/m 2.7 ) 44.7± ±11.9 NS Left ventricular ejection fraction* 0.65± ±0.08 NS Left ventricular hypertrophy* (%) Eccentric /Concentric hypertrophy (n) 37/5 52/10 NS * Left ventricular mass 47 g/m 2.7 in women and 50 g/m 2.7 in men P Table 2 Echocardiographic findings according to gender

10 Women (n=69) r P Men (n=80) r Age (yrs) h mean systolic BP (mm Hg) Office systolic blood pressure (mm Hg) h mean diastolic BP (mm Hg) NS Office diastolic blood pressure (mm Hg) NS 0.09 NS 24-h mean pulse pressure (mm Hg) Office pulse pressure (mm Hg) P Table 3 Correlation cefficients ( r ) between left ventricular mass and age or blood pressure values

11 a) Women (n=69) Men (n=80) Beta Coefficient P Beta Coefficient P Intercept Age NS Body mass index Diabetes NS Therapy NS NS 24-h mean systolic BP h mean diastolic BP NS b) Women (n=69) Men (n=80) Beta Coefficient P Beta Coefficient P Intercept Age NS Body mass index Diabetes NS Therapy NS NS 24-h mean pulse pressure Table 4 Multiple regression analysis with left ventricular mass as dependent variable, and both 24-h mean BPs a) or 24-h pulse pressure b) as independent variables.

12 Women (n=69) 95%CI Men (n=80) 95%CI 24-h mean systolic BP (mmhg) h mean diastolic BP (mmhg) h mean pulse pressure (mmhg) Office systolic blood pressure (mmhg) Office diastolic blood pressure (mmhg) Office pulse pressure (mmhg) Table 5 - Odds Ratio for LV hypertrophy (left ventricular mass 47 g/m 2.7 in women and 50 g/m 2.7 in men) estimated by every 1mmHg increase in blood pressure in both genders after adjusting for age, body mass index, diabetes, and therapy.

13 % of explained variance Other variables h mean pulse BP 24-h mean diast. BP 24-h mean syst. BP Women Men Women Men Figure 1- Percentage of explained variance of left ventricular mass in male and female subjects by 24h mean blood pressure. Other variables are age, body mass index, diabetes, and previous therapy.