Abody of evidence demonstrates that alcohol

BRIEF COMMUNICATIONS AJH 1998;11:230 234 The Effects of Alcohol Consumption on Ambulatory Blood Pressure and Target Organs in Subjects With Borderline to Mild Hypertension Olga Vriz, Diana Piccolo, Enrico Cozzutti, Loredano Milani, Renzo Gelisio, Fabrizio Pegoraro, Guido Garavelli, Daniele D Este, and Paolo Palatini, on behalf of the 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 agematched 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 > 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. Am J Hypertens 1998;11:230 234 1998 American Journal of Hypertension, Ltd. KEY WORDS: Alcohol, ambulatory blood pressure monitoring, target organ involvement. Abody of evidence demonstrates that alcohol consumption affects blood pressure (BP) levels, although there is no agreement on the relationship between alcohol and BP. 1,2 The association of alcohol intake with left ventricular hypertrophy (LVH) 3 and kidney abnormalities 4 has been investigated almost exclusively in heavy drinkers. In a recent report from the Framingham Study an association between alcohol intake and LV mass was found in moderate drinkers, independent of other risk factors. 5 Received July 17, 1997. Accepted September 29, 1997. From the Clinica Medica I, University of Padova, Padova, Italy. This paper was presented at the Twelfth Scientific Meeting of the American Society of Hypertension, May 27 to 31, 1997. Address correspondence and reprints requests to Prof. Paolo Palatini, trial coordinator, Clinica Medica I, University of Padova, Via Giustiniani 2, 35126 Padova, Italy. 1998 by the American Journal of Hypertension, Ltd. 0895-7061/98/$19.00 Published by Elsevier Science, Inc. PII S0895-7061(97)00463-9

AJH FEBRUARY 1998 VOL. 11, NO. 2 ALCOHOL S EFFECTS ON ABPM, TARGET ORGANS 231 The aim of the present study was to investigate whether alcohol intake has an association with LV mass and albumin excretion rate (AER), in a population of young subjects with borderline to mild hypertension, and to assess whether alcohol use has a different relationship with BP measured in the clinic and during 24-h ambulatory monitoring. METHODS Subjects We studied 793 consecutive male subjects, aged 18 to 45 years, from the HARVEST study, an ongoing trial of the predictive value of ambulatory BP monitoring for the development of fixed hypertension in subjects with borderline to mild hypertension, never treated. 6 Smoking status, coffee intake, and physical activity were assessed by a questionnaire, as described elsewhere. 6 Wine accounted for most of the alcohol intake in our population. The subjects were grouped according to their alcohol intake, expressed as grams of alcohol/day, according to the method of Criqui et al. 7 Alcoholics were excluded from the study. The men were divided into four groups: 1) nondrinkers, 2) those who drank 50 g/day (mild drinkers), 3) those who drank between 50 and 100 g/day (moderate), and 4) those who drank 100 g/day (heavy drinkers). As only eight subjects reported drinking 100 g/day, groups 3 and 4 were combined (moderate to heavy drinkers). Blood Pressure Measurement Office BP was considered as the mean of six readings taken in the supine position and recorded 2 weeks apart. Two 24-h ambulatory BP monitorings were performed 3 months apart, with either the A&D TM-2420 model 7 (A&D Company, Tokyo, Japan) or the ICR Spacelabs 90207 (Spacelabs Inc., Redmond, WA). Modalities of the ambulatory BP measurements and BP variables were reported in a previous paper. 8 During the 24-h recordings, urine was collected for the determination of catecholamines and microalbuminuria. Echocardiography The M-mode and two-dimensional echocardiographic methods were used. Left ventricular internal diameter and wall thickness were measured at end diastole, according to the recommendations of the American Society of Echocardiography. 9 Left ventricular parameters were derived as reported elsewhere. 10 All measurements were made independently by two experienced physicians at the coordinating center, according to the procedure described elsewhere. 10 Statistics The subjects were first divided into three groups. A first ANOVA test was performed. Categorical variables were tested by 2. As the subjects in the three groups differed greatly in age and body mass index, to assess the net effect of alcohol on BP and target organs the moderate to heavy drinkers were matched with the other two groups for age and between-group differences were compared with ANOVA. The values are expressed as mean SEM. P.05 was considered significant. The statistical analysis was done using the SAS UNIX, version 6.09, statistical package (SAS Inc., Cary, NC). RESULTS The 793 male subjects were divided into three groups: 364 were abstainers (group 1), 341 drank 50 g/day (group 2), and 88 drank 50 g/day (group 3). As the three groups of men were largely unbalanced for age, the 88 subjects of group 3 were compared with as many subjects of groups 1 and 2 matched for age. After matching, body mass index was no longer different among the three groups, but smoking habits were still significantly different according to alcohol intake ( 2 13.4, P.039). Office systolic BP was not affected by alcohol, whereas diastolic BP showed a U-shaped curve with a significant difference between groups 2 and 3 that remained significant after adjusting for smoking (Table 1). The 24-h and daytime systolic BPs showed a linear relationship with alcohol intake. The between-group differences were significant for group 1 v 3, even after adjusting for smoking. No between-group differences were observed for nighttime BPs (Table 1). No differences in ambulatory diastolic BPs were observed according to alcohol use. Daytime diastolic BP variability was higher in the group of moderate to heavy drinkers than in the nondrinkers. This difference was still significant even after adjusting for smoking (Table 1). Only high-density lipoprotein cholesterol was higher in group 3 than in the other two groups (Table 1). A progressive increase in urinary catecholamines was observed from group 1 to group 3, but the differences were not statistically significant (Table 1). Echocardiographic LV mass index increased progressively from the nondrinkers to the moderate to the heavier drinkers. The increase in LV mass index resulted mainly from the increase in wall thickness (1.90 0.02 mm, 1.91 0.02 mm, and 1.97 0.02 mm; P.03 for abstainers v moderate to heavy drinkers). The differences remained significant after adjusting for smoking and 24-h systolic and diastolic BPs also (P.03). Left ventricular internal diameter did not differ among the groups (Figure 1). In group 3, the AER was much higher than in the other two groups (9.4 8.1 mg/24 h, 11.2 8.2 mg/24 h, and 22.8 7.6 mg/24 h; group 1 v group 3 P.02). After adjusting for smoking the difference was still significant (P.04), but it was no longer significant when 24-h systolic and diastolic BPs were added to the model.

232 VRIZ ET AL AJH FEBRUARY 1998 VOL. 11, NO. 2 TABLE 1. CHARACTERISTICS OF THE THREE GROUPS OF MALE SUBJECTS MATCHED FOR AGE WITH DIFFERENT ALCOHOL CONSUMPTION Group 1 0 g/day) Group 2 < 50 g/day) Group 3 > 50 g/day) P Smoking (P) Age (years) 37.6 0.7 37.8 0.7 38.2 0.7 NS NS BMI (kg/m 2 ) 26.5 0.3 26.4 0.3 27.0 0.3 NS NS Office SBP (mm Hg) 145.4 1.1 144.8 1.0 147.5 1.0 NS NS Office DBP (mm Hg) 95.7 0.5 94.7 0.5 96.8 0.5 2 v 3.004 2 v 3.004 Office HR (beats/min) 73.6 0.9 72.9 0.9 73.4 0.9 NS NS 24-h SBP (mm Hg) 129.1 1.1 131.2 1.1 133.2 1.1 1 v 3.01 1 v 3.03 24-h DBP (mm Hg) 83.1 0.8 82.1 0.8 83.1 0.8 NS NS 24-h HR (beats/min) 71.2 0.9 71.0 0.9 73.9 0.9 1 v 3.03 1 v 3 NS 2 v 3.02 2 v 3.02 Day SBP (mm Hg) 132.3 1.2 134.4 1.2 136.2 1.2 1 v 3.02 1 v 3.047 Day DBP (mm Hg) 85.2 0.8 84.2 0.8 85.1 0.8 NS NS Day HR (beats/min) 74.0 1 73.3 1 76.3 0.9 2 v 3.03 1 v 3 NS 2 v 3.02 Night SBP (mm Hg) 117.1 1.3 118.1 1.3 120.1 1.3 NS NS Night DBP (mm Hg) 75.3 0.9 73.7 0.9 74.6 0.9 NS NS Night HR (beats/min) 61.1 0.9 61.5 0.9 63.8 0.9 1 v 3.03 NS Day SBP variability 13.0 0.4 13.1 0.4 14.0 0.4 NS NS Day DBP variability 9.7 0.2 10.0 0.2 10.4 0.2 1 v 3.02 1 v 3.04 HDL/cholesterol (mg/dl) 46.7 1.5 47.6 1.5 52.8 1.4 1 v 3.005 1 v 3.01 2 v 3.01 2 v 3.008 Epinephrine (mg/24 h) 22.0 3.0 25.7 3.4 28.2 3.2 NS NS Norepinephrine (mg/24 h) 86.5 8.2 89.3 9.0 94.6 8.3 NS NS Data are mean SEM. Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate. DISCUSSION In the present study the alcohol drinkers were older and heavier than the nondrinkers, in keeping with the results of other investigators. 2 In agreement with previous studies, they smoked more and drank more coffee than the abstainers. 11 After matching male drinkers for age the groups were more homogeneous also for body mass index, but differences in smoking habits were still present. Effects of Alcohol on Ambulatory BP Overall, the effect of alcohol intake on both office and ambulatory BP was rather modest in the region of 2 to 4 mm Hg, and smaller than that reported in most studies. This is likely because of our subjects having BP values found in a narrow range. Another possibility is that wine has a lower effect on BP than other alcoholic beverages, as reported by others. 12 However, the main aim of our investigation was to study the effect of alcohol on 24-h BP patterns and variability. In 10 normotensive subjects with alcohol consumption habits, Howes et al 13 found no difference in mean 24-h BP between a 4-day abstinence period and a 4-day drinking period, but did find an increase in BP variability.

AJH FEBRUARY 1998 VOL. 11, NO. 2 ALCOHOL S EFFECTS ON ABPM, TARGET ORGANS 233 FIGURE 1. Echocardiographic LV dimensional parameters in three groups of age-matched men with different alcohol consumption. Data adjusted for smoking. The results of the present study show that alcohol affects BP significantly during daytime hours, whereas during sleep little or no effect is detectable, with the increase in BP proportional to alcohol intake. Furthermore, in agreement with the results of the aforementioned authors, 13 daytime diastolic BP variability was significantly increased in the heavier drinkers, probably as a consequence of the vasoactive effects of alcohol. As reported by others, 2 the hypertensive effect of alcohol may be potentiated by other lifestyle factors such as smoking, calorie and sodium intake, and sedentary habits. In the present study, the daytime systolic BP difference between the heavier drinkers and the abstainers remained significant after adjusting for smoking, suggesting that the hypertensive effect of alcohol is not mediated by other lifestyle factors. Alcohol and Left Ventricular Mass We found a linear relationship between LV mass index, interventricular septum thickness, and wall thickness with alcohol intake even after adjusting for smoking, although the difference was significant only between abstainers and heavier drinkers. After adjusting for 24-h systolic and diastolic BP the trend remained the same, suggesting a direct hypertrophic effect of alcohol on the heart. A positive relation between alcohol and LV mass was reported in the Framingham Study, even after taking into account the effect of BP, 5 but not in other studies. 14 It is not really known whether moderate alcohol intake has a detrimental effect on the heart. Alcohol might affect LV thickness also through the increase in BP. However, in the present study the cardiac effect of alcohol was independent of mean 24-h systolic and diastolic BP. Alcohol has been reported to increase the sympathetic drive to the heart. 15 In the present study we found a progressive, though insignificant, increase in catecholamines from abstainers to moderate-heavy drinkers and higher values of 24-h heart rate in heavier drinkers. Thus it is possible that the higher values of left ventricular wall thickness are accounted for also by an increase in sympathetic activity. Effect of Alcohol on AER Albumin excretion rate was significantly affected by alcohol use, especially for doses 50 g/day. The effect was still present after adjusting for smoking but disappeared when ambulatory BP was included in the model. From our data it appears that the effect of alcohol on urinary albumin is mediated mainly by BP, but an additive direct effect of alcohol and smoking on glomerular permeability can

234 VRIZ ET AL AJH FEBRUARY 1998 VOL. 11, NO. 2 not be excluded. Recently, we demonstrated that AER is more closely related to ambulatory BP than to office BP. 16 In conclusion, we found that in mild hypertensive subjects alcohol has a linear relationship with ambulatory BP and a detrimental effect on the heart and the kidney. Although the increase in AER seems to be mediated mainly by the alcohol effect on BP, the increase in wall thickness appears to result from a direct effect of alcohol on the myocardium. ACKNOWLEDGMENTS We thank all the participants in the HARVEST study and President: C. Dal Palù; Vice President: A. C. Pessina; Trial Coordinator: P. Palatini. REFERENCES 1. Klatsky AL, Friedman GD, Armstrong MA: The relationship between alcohol use and other traits to blood pressure: a new Kaiser-Permanente study. Circulation 1986;73:628 636. 2. Keil U, Chambless L, Filipiak B, et al: Alcohol and blood pressure and its interaction with smoking and other behavioural variables: results from the MONICA Augsburg survey 1984 1985. J Hypertens 1991;9:491 498. 3. Mathews EC, Gardin JM, Henry WL, et al: Echocardiographic abnormalities in chronic alcoholics with and without congestive heart failure. Am J Cardiol 1981;47: 570 578. 4. Eiser AR: The effect of alcohol on renal function and excretion. Alcohol Clin Exp Res 1987;11:127 138. 5. Manolio TA, Levy D, Garrison RJ, et al: Relation of alcohol intake to the left ventricular mass: the Framingham Heart Study. J Am Coll Cardiol 1991;17:717 721. 6. Palatini P, Graniero GR, Mormino P, et al: Relation between physical training and ambulatory blood pressure in stage I hypertensive subjects. Results of the HARVEST trial. Circulation 1994;90:2870 2876. 7. Criqui MH, Wallance RB, Mishkel M, et al: Alcohol consumption and blood pressure. Hypertension 1981; 3:557 565. 8. Palatini P, Penzo M, Racioppa A, et al: Clinical relevance of nighttime blood pressure and of daytime blood pressure variability. Arch Intern Med 1992;152: 1855 1860. 9. Sahn DJ, DeMaria A, Kisslo J, et al: Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072 1083. 10. Palatini P, Bongiovì S, Cordiano R, et al: Ventricular ectopic activity in physically trained hypertensive subjects. Eur Heart J 1992;13:316 320. 11. Arkwright PD, Beilin L, Rouse I, et al: Effects of alcohol use and other aspects of lifestyle on blood pressure levels and prevalence of hypertension in a working population. Cirulation 1982;66:60 66. 12. Lang T, Cambien F, Richard JL, et al: Relation entre le niveau de pression arterielle et differents types de boissons alcooliques. Arch Mal Coeur Vaiss 1988;81:171 174. 13. Howes LG, Krum H, O Callaghan CJ, et al: Twentyfour hour ambulatory blood pressure profiles following regular alcohol consumption. Am J Hypertens 1992; 5:771 772. 14. Kupari M, Koskinen P: Relation of left ventricular function to habitual alcohol consumption. Am J Cardiol 1993;72:1418 1424. 15. Corea L, Bentivoglio M, Verdecchia P, et al: Left ventricular wall thickness and plasma catecholamines in borderline and stable essential hypertension. Eur Heart J 1982;3:164 170. 16. Palatini P, Graniero GR, Mormino P, et al: Prevalence and clinical correlates of microalbuminuria in stage I hypertension. Results from the hypertension and ambulatory recording Venetia study (HARVEST Study). Am J Hypertens 1996;9:334 341.