Prevalence of left ventricular hypertrophy in a hypertensive population

European Heart Journal (1996) 17, 143-149 Prevalence of left ventricular hypertrophy in a hypertensive population J. Tingleff, M. Munch, T. J. Jakobsen, C. Torp-Pedersen, M. E. Olsen, K. H. Jensen, T. Jorgensen and M. Kirchoff The Glostrup Population Studies, Department of Internal Medicine C, Glostrup County Hospital, University of Copenhagen, Denmark Aims This investigation was set up to study the prevalence of left ventricular hypertrophy in a hypertensive population with reference to a normotensive control group. From the general population 3498 men and women aged 35, 45, and years old were invited to a health examination. Participants with blood pressure above 160mmHg systolic or 95 mmhg diastolic or those taking antihypertensive medication or having done so during the previous 6 months were asked to undergo an echocardiographic examination. Normotensive controls were randomly selected from the same population. Of 2 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the Penn conventions and indexed for body surface. Cut-off values for left ventricular hypertrophy were 134 g. m ~ 2 for males and 102 g. m ~ 2 for women. Introduction The presence of left ventricular hypertrophy in hypertensive patients, diagnosed by electrocardiographic criteria, is associated with a risk of mortality from cardiovascular disease three times greater than the risk associated with hypertension alone 1 ' 1. When echocardiographic criteria for left ventricular hypertrophy are used, the prevalence of hypertrophy is much higher than when electrocardiographic (ECG) criteria are used, both in the general population and in hypertensive patients 12 ' 3 '. Echocardiographic left ventricular hypertrophy is also associated with increased risk of cardiovascular disease and death in hypertensive men' 41 and in the general population' 51. The prevalence of left ventricular hypertrophy determined by echocardiography in hypertensive patients has been reported to be 23% to 48%' 6-8 ', but Revision submitted 7 February 1995, and accepted 7 March 1995. Correspondence: Jens Tingleff, MD, Department of Cardiothoracic Surgery, University Hospital of Copenhagen, Rigshospitalet, 9-Blegdamsvej, DK.-2100 Copenhagen, Denmark. Results Overall, the prevalence of left ventricular hypertrophy was /20% (men/women) in normotensives and 25%/% in hypertensives (/ > <001). After subdivision by age and sex, there was a significant difference in the prevalence of left ventricular hypertrophy between normotensives and hypertensives only in the -year-old group (P<002 for males and P<005 for females). Conclusion The association between blood pressure and left ventricular hypertrophy in the general population is weak. Left ventricular hypertrophy is only significantly more frequent among hypertensives as compared to normotensives in older people. (Eur Heart J 1996; 17: 143-149) Key Words:, left ventricular hypertrophy, prevalence, echocardiography, general population. comparisons between left ventricular hypertrophy in hypertensives and normal subjects are hampered by a possible biased selection of both hypertensive patients and normal controls. In the present study, a random sample of the population was screened for hypertension. The prevalence of left ventricular hypertrophy denned by echocardiographic criteria in those with hypertension was investigated and the results compared with a randomly selected normotensive group among the same population. Methods Study population In 1982, a random sample of 4807 men and women, bora in 1922, 1932, 1942 or 1952, and living in the western part of Copenhagen County, was drawn from the Civil Registration System. Two hundred and twenty six subjects of foreign origin were excluded, reducing the sample to 4581. Of these, 3608 persons attended a general health examination. 0195-668X/96/OI0143 + 07 $12.00/0 1996 The European Society of Cardiology

1 J. Tingleffet al. By 1987, 110 subjects had died, leaving a total of 3498 who were asked to participate in a follow-up examination. This was attended by 2987 persons (85%). The remainder did not respond to our invitation or refused to be examined. Participants underwent a general health examination including measurement of blood pressure in the supine and sitting positions. Information on medical treatment of hypertension was obtained. All subjects in whom the blood pressure was above 160mmHg systolic and/or 95 mmhg diastolic and subjects who had received treatment for hypertension within the last 6 months were asked to undergo an echocardiographic examination. In subjects with normal blood pressure, but on antihypertensive medical treatment, records from the hospital/clinic which initiated the treatment were evaluated. As controls, a random subgroup of age- and gender-matched subjects were also asked to participate. Participants in this group were normotensive and had normal ECGs. For every two subjects with possible hypertension, one control was invited to participate. Of a total of 927 subjects asked to undergo an echocardiographic examination (609 suspected hypertensives, 318 controls), 6 accepted the invitation (72%) (438 suspected hypertensives, 227 controls). There was no difference between participants and non-participants as regards height, weight and blood pressure based on the data from the 1987 examination. Due to poor echocardiographic image quality, 113 participants (17%) were excluded. The final study population, therefore, consisted of 2 subjects (358 suspected hypertensives, 194 controls). Since the prevalence of hypertension in the age groups of 35 and 45 years was similar, the data from these two groups were pooled. Verbal informed consent was obtained from each participant before examination. The study protocol was approved by the ethics committee for Copenhagen County, and was in accordance with the Helsinki II declaration. Echocardiographic methods All studies were performed with a Toshiba model 60A echocardiograph equipped with a 3-4 MHz transducer. Standard M-mode echocardiography was performed at the tip of the mitral valve. M-mode examinations were guided by two-dimensional scan. Measurements were made according to the Penn conventions' 9 ' (mean value of three consecutive cardiac cycles) and was performed blind to other information on the participant. Left ventricular mass was calculated by the formula left ventricular mass=104 [(LVIDD + IVS + LVPW) 3 - (LVIDD) 3 ] - 13-6 g, where LVIDD denotes the diastolic left ventricular internal dimension (cm), IVS the diastolic interventricular septal thickness, and LVPW the diastolic left ventricular posterior wall. Because of the correlation between surface area and left ventricular mass observed in the normal population' 2101, all values reported here for left ventricular mass are mass per m 2 body surface area unless otherwise specified. Data from the Framingham study suggested cut-off values for left ventricular hypertrophy of 131 g.m" 2 for males and loog.rn" 2 for females' 71. Devereux et a/.'" 1, studying normal people at work and apparently normals attending a cardiology clinic, suggested cut-off values of 132-136 g. m"~ 2 for males and 109-112 g. m " 2 for females. Based on these studies, we chose cut-off values of 134 g. m ~ 2 for males and 102 g. m ~ 2 for females. To study the applicability of these results in our sample, we chose a 'super-normal' subpopulation, as was done in the Framingham study. We found 89 subjects with no known cardiac or pulmonary disease, no drug treatment, blood pressure below 140/90, and no over- or underweight (body mass index no deviating more than 20% of recommended). Blood pressure measurement All blood pressures were measured after at least 10 min in the sitting position. They were measured both at the general health examination by the auscultatory method with a Hauxley random-zero mercury manometer, and at the echocardiographic examination. Elevation of blood pressure was considered present when it exceeded 160 mmhg systolic and/or 95 mmhg diastolic (WHO criteria). Based on these measurements, the populations were divided into three categories: (1) Normotensives: normal blood pressure at the two examinations and no history of antihypertensive medical treatment within the last 6 months. (2) Doubtful hypertensives: subjects with elevated blood pressure on only one occasion with no history of medical antihypertensive treatment. (3) Hypertensives: subjects with elevated blood pressure on both examinations or subjects currently receiving antihypertensive medication for documented hypertension. Statistical analysis Analysis of contingency tables was performed with Chi 2 -test for 2x2 tables with continuity adjustment. In analysis of the relationship between blood pressure and left ventricular mass, Pearsons correlation coefficient, r, and its significance level was calculated. The SAS (SAS Institute, Inc., Cary, NC, U.S.A.) statistical package was used for calculations. Results In Table 1, gender, age and presence of hypertension is shown for 1987 responders, 1987 non-responders and those who had died since the 1982 examination. There were no significant differences between patients who participated and those who did not. The small group of deceased were older, more often male, and more often hypertensive.

LVhypertrophy in hypertensives 145 Table 1 Characteristics of the study population based on the examination in 1982 according to their response to the 1987 invitation 1982 population total n = 36O8 1987 responders n = 2987 (82-8%) Dead since 1982 n= 110 (3-0%) Non-responders n = 511 (14-2%) gender Age in 1982 (mean) 51% 11% -5 years % 31% 53-9 years 48% 11% 0 years Table 2 Final study population of 2 persons subdivided by age, gender and hypertension category. Number of individuals and prevalence of left ventricular hypertrophy is indicated Age (years) s Doubtful hypertension 35 or 45 All n=49 n = 39 18% n = 24 8% n=112 n = 30 23% n = 23 17% n = 29 17% n = 82 20% Table 3 Characteristics of thestudy population of 2 persons Weight (kg) Height (m) BMI (kg.m" BSA (m 2 ) 2 ) Systolic BP (mmhg) Diastolic BP (mmhg) LVM (g) LVM/BSA (g. m" 2 ) n=112 78 (59-101) 4 (1--1-83) (20-32) 1-9 (1-6-2-2) 132 (110-159) 83 (69-90) 181 (73-297) 94 (41-146) n = 20 25% n = 23 9% n=17 41% n = 60 23% n = 82 62 (48-84) 1-62 (1-50-6) 24 (19-29) (1-4-1-9) 134 (103-157) 83 (67-90) 138 (73-235) 83 (40-136) n=12 33% n=18 28% n=13 54% n = 43 37% Doubtful hypertension n = 60 80 (60-107) 5 (1-68-1 86) (21-34) 20 (-2-3) 168 (120-170) 88 (68-108) 207 (79-352) 108 (41-172) 19% n = 56 39% n=142 25% 68 (51-89) 1-63 (1-53-6) (20-32) (1-5-2-0 143 (108-169) 88 (76-110) 166 (64-287) 99 (40-166) n = 29 n = 34 24% n = 50 34% n=l 13 % 84 (66-107) 5 (1-64-1-88) 27 (21-35) 20 (-2-3) 160 (131-189) 101 (83-120) 228 (107-410) 114 (54-208) n=142 69 (52-99) 1-61 (1-52-1 73) 27 (20-38) (1-5-2-0) 160 (132-200) 98 (80-116) 159 (-286) 92 (37-166) n = 314 81 (62-103) 5 (1-1-87) (21-34) 2-0 (-2-2) 151 (116-181) 92 (73-114) 207 (85-369) 106 (45-183) All n = 238 66 (49-89) 1 62 (1-52-4) 25 (20-33) (2-0-1-5) 148 (110-185) 91 (72-112) 153 (-279) 90 (40-154) The composition of the final study population is shown in Tables 2 and 3. (elevated blood pressure on two occasions or on drug therapy for hypertension) was found in 2 subjects. Of these, 130 (51%) were on anti-hypertensive treatment and in this group, normal systolic and diastolic blood pressure on both examinations was recorded in 80% and 74%, respectively. There were 103 subjects in the category 'doubtful hypertension' (elevated blood pressure on only one occasion). blood pressure on both occasions, normal ECG and no history of hypertension were found in 194 subjects. Subjects in the hypertensive groups have a tendency to be more obese than those in the normotensive groups (Table 3). Overall correlation between blood pressure and left ventricular mass is shown graphically in Fig. 1. Left ventricular mass per m 2 body surface area was correlated with diastolic blood pressure with r=0-18 and with systolic blood pressure with r=0-25. In both cases P=00001.

146 J. Tingleffet al. Systolic blood pressure (mmhg) 250 The prevalence of left ventricular hypertrophy is shown in Table 2. When all age groups were pooled, left ventricular hypertrophy was significantly more frequent in hypertensives compared to normotensives in both sexes (/ 3 <001). There was a tendency to lower prevalence of left ventricular hypertrophy in normotensives with higher age. For hypertensives, the opposite was seen (higher prevalence of left ventricular hypertrophy in the older age group). Therefore, by subdividing the subjects into sex and age groups, a significant difference between normotensives and hypertensives was found in the -year-old age group (men P<0-02 and women In the small super normal group of patients, there were 45 males and females. For males, LVM. m ~ 2 was mean 86 g. m " 2 and the standard error was 39. For females, LVM. m ~ 2 was 80 g. m ~ 2 and the standard error was 27. These results are very similar to the studies' 7 " 1 from which we chose cut-off values with respect to mean values. The values of standard error observed in our small subgroup was greater. Similar results were obtained when left ventricular mass was analysed as a continuous variable (adjusted for body surface area). Significant differences between participants with no hypertension, doubtful hypertension, and hypertension were only observed in the - year-old age group (/ > =001 for men and / > =002 for women). In the younger age groups, the minimal /"-value was 0-36. The prevalence of left ventricular hypertrophy was studied in the 2 persons categorised as hypertensives and subdivided according to treatment. Among 1 subjects with untreated hypertension, 36% had left ventricular hypertrophy. Among 45 subjects receiving antihypertensive medication but categorised as hypertensives on blood pressure criteria, 40% had left ventricular hypertrophy. Among 84 persons with normal

LVhypertrophy in hypertensives 147 250 200-150 - a ho 100 - Figure 1 (b) 100 150 Systolic blood pressure (mmhg) 200 250 Figure 1 The relationship between blood pressure (x-axis) and left ventricular mass per body surface area (g. m ~ 2 ) (y-axis), in systolic (a) and (b) diastolic pressure (mmhg). blood pressure but receiving antihypertensive medication for documented hypertension, 30% had left ventricular hypertrophy. These figures do not differ significantly and in this study, a relationship between antihypertensive medication and prevalence of left ventricular hypertrophy could not be seen. Most hypertensives were treated with diuretics, some with beta-blockers, and very few with calcium antagonists and angjotensin converting enzyme inhibitors. Discussion The population studied was selected in 1982 and underwent an initial examination in that year and a re-examination in 1987. Of the initial study group, 110 had died before undergoing re-examination, but we do not believe this introduces bias. In the present study, the sample size was influenced but not the composition of the unselected population at the time of the reexamination. The fact that those who had died in the intermediate period more often had hypertension introduces a clear bias when results in different age groups are compared. With respect to a cross-sectional study as that performed in 1987, the bias introduced is no greater than if the slightly smaller sample were selected from the whole population. The difference between this study and a study initiated in 1987 is that the bias of comparison of age groups is documented. At the new examination, 85% accepted the invitation and the prevalence of hypertension did not differ between participants and nonparticipants. For these reasons we consider the sample population as representative as possible. Although electrocardiographic detection of left ventricular hypertrophy has been used for epidemiological studies, echocardiographic evidence of left ventricular hypertrophy has proven to be a much more sensitive and specific method to measure left ventricular mass 112 '.

148 J. Tingleffet al. Table 4 Mean, standard deviation (SD), median 5th percentile (5%) and 95th percentile (95%) of left ventricular mass as g. m~ 2 surface area subdivided by gender, age and hypertension category. =possible hypertension Gender Age (years) Category Mean SD Median 5% 95% 35 + 45 35 + 45 35 + 45 35+45 35+45 35+45 95 96 99 94 99 111 90 132 129 86 94 87 82 86 90 80 117 97 33 40 34 38 34 41 32 50 28 36 27 28 36 36 34 43 41 93 92 95 97 102 107 97 120 114 85 100 85 81 74 82 72 115 88 37 30 49 41 51 48 40 33 35 37 66 37 153 172 162 158 147 195 136 259 245 135 153 139 134 161 154 141 213 175 Epidemiological studies of left ventricular mass should, therefore, mainly be based on echocardiographic findings. In addition to the relationship of left ventricular mass to hypertension, there are important links between left ventricular mass and body size measurements such as weight, height and body surface area' 131. In our study, we indexed left ventricular mass to body surface area. This is a well accepted method used in others studies' 5 ' 61. The prevalence of echocardiographic left ventricular hypertrophy is mainly based on studies in the hypertensive population with reference to normotensive subjects. These studies suggest that the prevalence of left ventricular hypertrophy is 23% to 48% in hypertensives' 5 ' 14 ' 151, with a higher prevalence in elderly patients with well controlled hypertension' 16 '. The overall prevalence in the general population with and without hypertension has been suggested to be 16% and 19% for men and women, respectively 1171. In our study, we found the prevalence of left ventricular hypertrophy to be /20% (men/women) in normotensives and 25%/% in the hypertensive population. The difference between our results and those previously reported could be due to selection criteria. In some studies, the hypertensive population consisted of highly selected patients attending a particular clinic having mild uncomplicated hypertension 151, or 140 mmhg systolic and/or 90 mmhg diastolic blood pressure was used as a cut off value 1 ' 3 ' 14 '. We reported the prevalence of left ventricular hypertrophy in an unselected hypertensive population, and used the WHO recommendation for definition of hypertension. We found a relatively high prevalence of left ventricular hypertrophy in normotensives, particularly in the younger age groups. In some respects, we believe this reflects the value in a non-selected normotensive population. Our mean left ventricular mass index for normotensives was 94 g. m~ 2 for men and 83 g. m~ 2 for women (Table 3), which is in accordance with the findings of others' 6 ' 7 "'. Therefore, the discrepancy with other studies in frequency of left ventricular hypertrophy in the normal population was unlikely to be due to measurement problems. The frequency of left ventricular hypertrophy in a subgroup is sensitive to the cut-off value for normal mass. The cut-off values used in this investigation were taken from the Framingham study' 71 and from a study by Devereaux et a/.'" 1. We tested whether these values were appropriate in our population. Using a similar normal population as described in the Framingham study 171, we found 89 super normal individuals. Mean LVM. m~ 2 was similar in our normal population and that of Framingham/Devereaux, but the standard deviation was greater in our population. However, our population of super-normals was small and therefore, we decided to use the previously published values. The principal results of this study are not sensitive to the chosen cut-off values, as similar results were obtained when left ventricular mass was used as a continuous variable. Similar to others studies, we found a weak overall correlation between blood pressure and left ventricular hypertrophy 121. The correlation was highly significant because of the many data available, but the r-values of approximately 0-2 indicate that only about 5% of the variation in left ventricular mass can be accounted for by linear correlation with blood pressure. The correlation to blood pressure may be stronger when 24 h ambulatory blood pressure monitoring is used" 81. A significant difference in left ventricular hypertrophy between normotensives and hypertensives was

LV hypertrophy in hypertensives 149 found only in the -year-age group. It is interesting to speculate whether this reflects the notion that hypertension needs to be present for a long time to induce left ventricular hypertrophy. However, as illustrated by the analysis of participants who had died since 1982, comparison between the age groups is biased. Left ventricular hypertrophy in essential hypertension can be reversed by medical treatment. Centrally acting alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel antagonists induce an effective reduction in left ventricular mass, whereas the vasodilators, diuretics and beta-adrenergic blockers do not have this effect' 19 ' 20 '. Although there was a tendency toward a lower prevalence of left ventricular hypertrophy between successfully and unsuccessfully medically treated patients, this difference did not become significant. In our hypertensive population, diuretic and beta-adrenergic drugs were used almost universally as antihypertensive treatment, and this may explain the lack of difference in prevalence of left ventricular hypertrophy between treated and non-treated subjects. In conclusion, we found that in younger age groups there is no difference in the prevalence of left ventricular hypertrophy between normotensives and hypertensives. With increasing age there is a moderate but significant relation to hypertension. References [1] Kannel WB. Prevalence and natural history of electrocardiographic left ventricular hypertrophy. Am J Med 1983; 75: 4-11. [2] Savage DD, Garrison RJ, Kannel WB et al. The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study. Circulation 1987, 75: i 33. [3] Savage DD, Drayer JI, Henry WL et al. Echocardiographic assessment of cardiac anatomy and function in hypertensive subjects. Circulation 1979; 59: 623-32. [4] Casale PN, Devereux RB, Milner M et al. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105: 173-8. [5] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561-6. [6] Hammond 1W, Devereux RB, Alderman MH et al. The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed persons with uncomplicated hypertension. J Am Coll Cardiol 1986; 7: 639-50. [7] Levy D, Savage DD, Garrison RJ, Anderson KM, Kannel WB, Castelli WP. Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol 1987; 59: 956-60. [8] Laufer E, Jennings GL, Korner PI, Dewar E. Prevalence of cardiac structural and functional abnormalities in untreated primary hypertension. 1989; 13: 151-62. [9] Devereux RB, Reicheck N. Echocardiographic determination of left ventricular mass: Anatomic validation of the method. Circulation 1977; : 613-18. [10] Devereux RB, Alonson DR, Lutas EM et al. Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings. Am J Cardiol 1986; 57: 450-8. [11] Devereux RB, Lutas EM, Casale PN et al. Standardization of M-mode echocardiographic left ventricular. J Am Coll Cardiol 1984; 4: 1222-30. [12] Reickek N, Devereux RB. Left ventricular hypertrophy: relationship of anatomical, echocardiographic, and electrocardiographic findings. Circulation 1981; 63: 1391-8. [13] Devereux RB. Left ventricular mass in children and adolescents J Am Coll Cardiol 1988; 12: 709-10 [14] Devereux RB, Savage DD, Drayer JI, Laragh JH. Left ventricular hypertrophy and function in high, normal, and low-renin forms of essential hypertension. 1982; 4: 524-31. [15] Devereux RB, Pickering TG, Harshfield GA et al Left ventricular hypertrophy in patients with hypertension: importance of blood pressure response to regularly recurring stress. Circulation 1983, 68: 470-6. [16] Jones E, Morgan TO, Califiore P, Johns J. Prevalence of left ventricular hypertrophy in elderly patients with well controlled hypertension. Clin Exp Pharmacol Physiol 1990; 17: 207-10. [17] Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC,Castelli WP. Echocardiographically detected left ventricular hypertrophy: Prevalence and risk factors. Ann Int Med 1988; 108:7-13. [18] Verdecchia P, Schillaci G, Guerrieri M et al. Orcadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990; 81: 528-36. [19] Liebsen PR. Clinical studies of drug reversal of hypertensive left ventricular hypertrophy. Am J Hypertens 1990; 3: 512-17. [20] Ram CV. Regression of left ventricular hypertrophy in hypertension with alpha-adrenergic blockade: physiological basis and therapeutic implications. J Hypertens 1987; 7 (Suppl): s98-9.