Pieralberto Visentin

Changes in Left Ventricular Anatomy and Function in Hypertension and Primary Aldosteronism

We investigated the effects on the heart of hypertension due to the excess of aldosterone and suppression of the renin-angiotensin system caused by primary aldosteronism with M-mode echocardiography and transmitral Doppler flow velocity measurements. We studied 34 consecutive patients with primary aldosteronism and 34 with essential hypertension individually matched for age, gender, race, body mass index, blood pressure values, and duration of hypertension. The groups were similar in age, body mass index, blood pressure, and duration of hypertension. However, lower serum potassium levels (3.5 +/- 0.6 versus 4.1 +/- 0.2 mmol/L, P < .0001) and plasma renin activity (0.53 +/- 0.45 versus 1.82 +/- 1.59 ng Ang I x mL-1 x h-1, P < .0001) and higher plasma aldosterone levels (1107 +/- 774 versus 206 +/- 99 pmol/L, P < .0001), left ventricular wall thickness, and left ventricular mass index (112 +/- 4.7 versus 98 +/- 3.7 g/m2, P = .029) were found in patients with primary aldosteronism compared with those with essential hypertension. Similarly, the PQ interval was longer (173 +/- 20 versus 141 +/- 14 milliseconds, P < .001) in primary aldosteronism than in essential hypertension patients. Significantly more primary aldosteronism than essential hypertension patients had left ventricular hypertrophy or left ventricular concentric remodeling (50% versus 15%, chi 2 = 11.97, P = .007). Both the E wave flow velocity integral (1063 +/- 65 versus 1323 +/- 78, P = .013) and the E/A integral ratio (0.91 +/- 0.05 versus 1.25 +/- 0.08, P < .001) were lower, and atrial contribution to left ventricular filling was higher (53.3 +/- 1.5% versus 45.5 +/- 1.3% P < .001) in patients with primary aldosteronism compared with essential hypertension patients. After 1 year of follow-up, highly significant decreases of left ventricular wall thickness and mass were observed in patients treated with surgical excision of an aldosterone-producing tumor, but not in those with medical therapy. Thus, in patients with primary aldosteronism, the excess aldosterone with suppression of the renin-angiotensin system is associated with both increased left ventricular mass and significant changes of left ventricular diastolic filling. The former changes appear to be reversible on removal of the cause of excessive aldosterone production.

Relation between physical training and ambulatory blood pressure in stage I hypertensive subjects. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.

BACKGROUND This study was undertaken to assess whether ambulatory blood pressure (BP) in a population of stage I hypertensive individuals was lower in the subjects performing regular exercise training. METHODS AND RESULTS The study was carried out in 796 young hypertensive patients (592 men) who had never been treated who took part in the HARVEST trial. The diagnosis of stage I hypertension was made on the basis of six office BP measurements. Subjects underwent noninvasive 24-hour ambulatory BP monitoring, 24-hour urine collection for catecholamine assessment, and echocardiography (n = 457). They were classified as exercisers if they reported at least one session of aerobic sports per week and as nonexercisers if they did not engage regularly in sports activities. Age (P < .0001), body mass index (P = .002), 24-hour heart rate (P < .0001), alcohol intake (P = .02), smoking (P = .02), and norepinephrine output (P = .04) were lower in the active (n = 153) than the inactive (n = 439) men. Physically active men exhibited a lower 24-hour and daytime diastolic BP than the inactive men, while there were no group differences in office BP or in nighttime diastolic BP and in ambulatory systolic BP. The between-group ambulatory diastolic BP difference remained statistically significant after adjustment for age, body mass index, alcohol intake, and smoking (P < .0001). Of the nonexercisers, 46.2% were confirmed hypertensives, compared with only 26.8% of the exercisers (P < .0001), on the basis of daytime diastolic BP. Echocardiographic left ventricular dimensional and functional indexes were similar in the two groups of men. Similar findings were shown by the 16 women who engaged in aerobic sports. CONCLUSIONS These data suggest that participation in aerobic sports may attenuate the risk of hypertension in young subjects whose office BP is in the stage I hypertensive range at office measurement.

Regular physical activity prevents development of left ventricular hypertrophy in hypertension

AIMS The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well known. We did a prospective study to investigate the long-term effect of regular physical activity on development of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension. METHODS AND RESULTS We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatment. LVH was defined as an LV mass >/=50 g/m(2.7) in men and >/=47 g/m(2.7) in women. During a median follow-up of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P = 0.000). In a logistic regression, physically active groups combined (n = 173) were less likely to develop LVH than sedentary group with a crude OR = 0.15 (CI, 0.05-0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass, blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07-0.85). Blood pressure declined over time in physically active subjects (-5.1 +/- 17.0/-0.5 +/- 10.2 mmHg) and slightly increased in their sedentary peers (0.0 +/- 15.3/0.9 +/- 9.7 mmHg, adjusted P vs. active = 0.04/0.06). Inclusion of changes in blood pressure over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR = 0.25, CI, 0.07-0.87). CONCLUSION Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.

Alpha-adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity

Objective Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. Methods We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen M235T and α-adducin Gly460Trp polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. Results The α-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P = 0.006). Patients homozygous for the Trp allele of that polymorphism had a LV mass index (123.4 ± 10.5 g/m2) significantly higher compared with heterozygotes (90.8 ± 2.5 g/m2, P < 0.01) or Gly homozygotes (94.7 ± 1.7 g/m2, P < 0.05). These subjects also have significantly lower PRA (F = 4.2, P = 0.017). Albeit uncommon, 40% of Trp homozygotes of the α-adducin polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0–82.1). Conclusions The homozygotic state of the Trp allele of α-adducin Gly460Trp polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin–angiotensin system in hypertensive patients.

Structural Abnormalities and Not Diastolic Dysfunction Are the Earliest Left Ventricular Changes in Hypertension

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

Left Ventricular Performance in the Early Stages of Systemic Hypertension

Abstract To investigate whether and how frequently left ventricular (LV) systolic performance assessed with endocardial and midwall measurement is depressed in young subjects with mild systemic hypertension, we studied 722 borderline to mild hypertensive patients (mean age ± SEM 33 ± 0.3 years, mean office blood pressure (BP) 146 ± 0.4/94 ± 0.2 mm Hg) enrolled in the Hypertension and Ambulatory Recording Venetia Study and 50 normotensive controls with similar age and sex distribution. BP was measured with 24-hour ambulatory monitoring. LV dimensional and functional indexes were assessed by M-mode echocardiography and sympathetic activity from 24-hour urinary catecholamines. In 64 hypertensive subjects (8.9%) the LV midwall shortening-stress relation was

Endocardial versus midwall measurement of left ventricular function in mild hypertension: an insight from the Harvest Study.

Objective To compare endocardial and midwall measurement of left ventricular fractional shortening in assessing cardiac systolic function in hypertension. Setting Seventeen hypertension clinics in northeast Italy. Main outcome measures Left ventricular endocardial fractional shorteningcircumferential stress relationship versus midwall shortening-stress relationship in the subjects divided according to relative wall thickness (RWT) and left ventricular mass indexed by body surface area. Patients Borderline-to-mild hypertensives [n = 635, aged 33 ± 0.3 years (mean ± SEM), office blood pressure 146 ± 0.4/94 ± 0.2 mmHg (means ± SEM)] in the Harvest Study and 50 normotensive controls with similar age and sex distributions. Methods Blood pressure was measured by 24 h ambulatory monitoring. Left ventricular dimensional and functional indices were assessed by M-mode echocardiography. Results In the subjects divided into quintiles of RWT, the left ventricular shortening-stress relationship was increased in a parallel fashion when calculated by endocardial and by midwall measurements for RWT ≤ 0.35. Instead, for greater RWT values (≥0.37) endocardial measurement constantly gave larger values than did midwall measurement. Both the endocardial and the midwall shortening-stress relationships progressively decreased with increasing RWT. However, the endocardial shortening-stress relationship remained greater than normal at any RWT, whereas the midwall shortening-stress relationship was decreased for RWT ≤0.37. In a multiple-regression analysis RWT was the most potent predictor of the endocardialmidwall shortening difference, left ventricular mass and 24 h systolic blood pressure being the second and third most potent predictors. Conclusions We found a parallel increase in indices of cavity emptying and of myocardial contractility in mild hypertensive subjects with normal left ventricular geometry. When the RWT is increased, ejection phase indices may be normal in the presence of decreased myocardial contractility.

PREMENOPAUSAL WOMEN ARE AT HIGHER RISK OF HYPERTENSIVE COMPLICATIONS THAN MEN: PP.35.455

Objective: Little is known about whether hypertension has a different impact on target organs in young to middle-age women compared to men. The purpose of this study was to describe sex-specific differences in target organ involvement in a cohort of never treated hypertensive subjects followed for a median of 7 years. Design and Methods: Participants were 626 adults (451 men) aged 18 to 45 years screened for stage 1 hypertension. Ambulatory blood pressure (BP) at entry was 127.5 ± 12.5/83.7 ± 8.2 mmHg in women and 131.9 ± 10.3/81.0 ± 7.9 mmHg in men. Patients were seen every six months for BP and global risk assessment until they needed drug therapy according to current guidelines. Ambulatory BP, albuminuria, and echocardiographic data (n = 470) were obtained at entry, every 5 years, and/or before starting treatment. Data were adjusted for age, body mass, BP, physical activity, parental hypertension, smoking, coffee and alcohol use. Results: Female gender was a significant predictor of urinary albumin (p = 0.002) and left ventricular mass indexed to height (LVMI,p = 0.002) at final assessment. At follow-up end, microalbuminuria was more common among women than men (13.7% versus 6.2%, adjusted p = 0.001) as was left ventricular hypertrophy (LVH, 26.4% versus 8.8%, p < 0.0001). These differences remained significant also when adjusted for baseline urinary albumin or LVMI. In a multivariable Cox analysis, female gender was a significant predictor of time to development of microalbuminuria (p = 0.002) with a HR(95%CL) of 2.6(1.4–4.7), and of LVH (p = 0.01) with a HR of 2.1(1.2–3.8). After inclusion of BP changes over time in the models, HRs were 3.2(1.7–5.9) and 2.7(1–5–5.1), respectively. When baseline urinary albumin or LVMI were taken into account, the associations remained highly significant with HRs of 2.7(1.4–5.1) and 2.5(1.3–4.6), respectively. Conclusions: These data show that in young-to-middle-age hypertensive subjects the risk of target organ damage is much greater among women than men irrespective of the BP changes over time. This raises the question about whether early antihypertensive treatment should be considered for premenopausal women.