G protein beta3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension.

BACKGROUND: A nucleotide substitution (C-->T) at position 825 of the gene GNB3 encoding the beta3 subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives. PROCEDURES: Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. RESULTS: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 +/- 1.5 v 89.7 +/- 1.5 g/m2; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity. CONCLUSIONS: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.

White-coat hypertension: a selection bias? Harvest Study Investigators. Hypertension and Ambulatory Recording Venetia Study.

BACKGROUND: Results of several studies have shown that subjects with white-coat hypertension (WCH) have more target-organ damage than do normotensive controls with similar ambulatory blood pressures. OBJECTIVE: To investigate whether this is due to a selection bias. SETTING: Seventeen hypertension clinics in northeast Italy. MAIN OUTCOME MEASURES: Echocardiographic data in relation to WCH status. PATIENTS AND METHODS: Mild hypertensive subjects from the HARVEST (n = 565) who underwent two ambulatory blood pressure monitorings 3 months apart and M-mode echocardiography, and 95 normotensive control subjects. RESULTS: From first ambulatory monitoring, 90 hypertensive subjects were classified as having WCH (mean daytime blood pressure < 130/80 mmHg). Their 24 h blood pressure was similar to that of the normotensive subjects, but their left ventricular mass index was greater. From second ambulatory monitoring, only 38 of the 90 subjects still had WCH, whereas 24 h blood pressure in the other 52 had risen beyond the limit of WCH. Left ventricular mass index (89.2 +/- 2.4 g/m2), wall thickness (18.1 +/- 0.3 mm), and relative wall thickness (0.359 +/- 0.006%) of the 38 subjects with WCH at both recordings were still greater than those of the normotensive subjects (82.4 +/- 1.5 g/m2, P = 0.02; 17.2 +/- 0.2 mm, P = 0.002; and 0.337 +/- 0.004%, P = 0.025) and similar to those of the 52 subjects who no longer had WCH (88.5 +/- 2.0 g/m2, 18.7 +/- 0.2 mm, and 0.375 +/- 0.005%, all NS). CONCLUSIONS: Owing to regression toward the mean, over 50% of the subjects with WCH could no longer be classified as such from repeated ambulatory monitoring, indicating that the current diagnosis of WCH is subject to selection bias. Cardiac remodeling was present also in the subjects confirmed to have WCH by repeated blood pressure recording, suggesting that the effect of WCH has an actual impact on target organs.

Structural abnormalities and not diastolic dysfunction are the earliest left ventricular changes in hypertension. HARVEST Study Group.

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.

The effects of alcohol consumption on ambulatory blood pressure and target organs in subjects with borderline to mild hypertension. HARVEST Study Group.

The objective of this study was to examine the relationship of alcohol consumption to target organ involvement and ambulatory blood pressure (BP) in a population of young borderline to mild hypertensive subjects. Participants were 793 male subjects, aged 18-45 years, from the HARVEST Study. The analysis was performed in three age-matched groups with similar body mass index. Casual and 24-h ambulatory BP monitoring, routine biochemistry, echocardiography, and albumin excretion rate were measured. The men were divided into three groups: 1) nondrinkers, 2) drinkers of < 50 g/day, and 3) drinkers of > or = 50 g/day. Office systolic BP was not significantly different among the three groups, whereas 24-h and daytime BPs increased progressively from the first to the third group (group 1 v 3; P = .01 for 24-h systolic BP and P = .02 for daytime systolic BP). These differences remained significant even after adjusting for smoking. Left ventricular mass index, interventricular septum thickness, and wall thickness increased progressively from group 1 to group 3; this difference also remained significant after adjusting for smoking and 24-h BPs. The albumin excretion rate was much higher in group 3 than in group 1 (P = .003), but when 24-h BP was added to the model the difference was no longer significant. These results indicate that alcohol has a detrimental effect on the heart and the kidney. Alcohol's effect on LV wall thickness appears to be direct, whereas its action on albumin excretion rate seems to be mediated mainly by its effect on BP.

Left ventricular performance in the early stages of systemic hypertension. HARVEST Study Group. Hypertension and Ambulatory Recording Venetia Study.

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 < 95% of the confidence interval in 50 normotensive controls. Subjects with depressed LV myocardial function had age, duration of hypertension, and LV mass similar to those of hypertensives with normal performance, and greater relative wall thickness (0.42 vs 0.37, p < 0.001). Stroke volume and cardiac output were lower (p < 0.001) in the former group. Among these 64 subjects, endocardial performance was depressed in 35 (group 1) and normal in 29 (group 2). Group 2 subjects had greater posterior wall (10.0 vs 9.5 mm, p = 0.03), ventricular septum (10.6 vs 10.1 mm, p = 0.05), and relative wall (0.44 vs 0.40, p < 0.001) thicknesses than group 1 subjects. Urinary norepinephrine was 50% higher in group 2 subjects (106 vs 70 g/24 hours, p = 0.03). Stroke volume and cardiac output were similar in both groups. In conclusion, these results show that LV contractility may be depressed in young subjects with borderline to mild hypertension.

Target organ damage and ambulatory blood pressure in stage I hypertension. The Hypertension and Ambulatory Recording Venetia Study.

According to recent international guidelines the decision on whether to treat young subjects during the early phase of hypertension should be based not only on their office blood pressure but also on their ambulatory blood pressure and whether target organ damage has occurred. Few data on the prevalence of hypertensive complications in young subjects with mild hypertension are available. In the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter trial conducted in northeast Italy, the percentage of young borderline-to-mild hypertensive subjects with echocardiographic left ventricular hypertrophy was 4.5% and the percentage with concentric remodeling was 4%. Clear differences in cardiac size and geometric adjustment to ambulatory systolic pressure between the two sexes were found. The impact of blood pressure on the walls of the left ventricle and on the left ventricular mass was remarkable in women but weak in men. The assessment of left ventricular systolic function confirmed that many young mild hypertensive subjects have an increased ejective performance. The left ventricular contractility evaluated by midwall measurement was, however, found to be depressed in 9.2% of the HARVEST participants. Their left ventricular diastolic function was similar to that of 50 normotensive controls. The prevalence of microalbuminuria [albumin excretion rate (AER) > 30 mg/24 h) was 6.1%, only slightly higher than that found by other authors among normotensive subjects and much lower than that observed among patients with more severe hypertension. For our stage I hypertensives, however, the AER was correlated to the 24 h blood pressure with high statistical significance, whereas we found no relationship between the AER and left ventricular mass index either for all of the subjects taken together or for the men and women considered separately. The results suggest that renal and cardiac involvement do not occur in parallel during the initial phase of hypertension.

[Alcohol consumption, arterial pressure and metabolic parameters in a population of borderline hypertension subjects. The results of the HARVEST Multicenter Study. Hypertension and Ambulatory Recording Venetia Study]. / Consumo di alcol, pressione arteriosa e parametri metabolici in una popolazione di soggetti con ipertensione borderline. Risultati dello Studio Policentrico HARVEST.

In 544 borderline to mild hypertensive subjects (mean age 33.5 +/- 8.6 years) participating in the HARVEST trial the relationship between alcohol consumption, blood pressure levels and several clinical parameters was examined. Subjects were divided into 3 groups according to whether they did not drink (Group 1, n = 171) or their daily alcohol intake was < 50 g (Group 2, n = 184) or > 50 g (Group 3, n = 54). In the 409 men alcohol consumption was related to age (p < 0.0001), body weight (p < 0.05) and coffee consumption (p < 0.0001). Group 3 drinkers were also more sedentary than the 2 other groups (p < 0.05). Both office (p < 0.001) and 24-hour (p < 0.001) diastolic blood pressure were greater in the drinkers than in the non drinkers, while no difference was observed in systolic blood pressure. Twenty-four-hour heart rate was higher in Group 3, but urinary catecholamines were similar in the 3 groups of men. Blood glucose (p < 0.001), total cholesterol (p = 0.001) and triglyceride (p < 0.005) were related to alcohol consumption, while HDL-cholesterol was not different in the 3 groups. Albumin excretion rate and uricemia were also unrelated to alcohol intake. In the 135 women a similar alcohol-related trend was observed for office diastolic blood pressure and for the metabolic parameters. In conclusion, the results of the present study confirm the association between alcohol consumption and blood pressure levels, which was apparent also within a population of borderline to mild hypertensive subjects and stress the role of alcohol in determining an abnormality of the metabolic parameters.