Left Ventricular Hypertrophy in HypertensionPrevalence and Relationship to Pathophysiologic Variables

RICHARD B. DEVEREUX, THOMAS G. PICKERING, MICHAEL H. ALDERMAN, SHU CHIEN,

JEFFREY S. BORER, AND JOHN H. LARAGH

SUMMARY In less than a decade since development of echocardiographic measurement of left ventricularmuscle mass, studies using this technique have provided considerable information about the prevalence andpathophysiology of left ventricular hypertrophy in human hypertension. Increased left ventricular mass has beenfound in a significant minority of patients with systemic hypertension, with the exact prevalence dependent bothon how a population is selected and on the sex, race, and possibly age composition of its members. All publishedstudies have reported that left ventricular hypertrophy is more closely related to blood pressure recorded in thepatient's natural setting during normal activity or exercise — whether measured by portable recorder or homemanometer — than to blood pressure measured by the physician. In addition, studies indicate that the classichypertensive abnormalities of concentric left ventricular hypertrophy and increased peripheral resistance areinterrelated, while left ventricular hypertrophy is absent in a subgroup of patients with mild essential hyperten-sion who exhibit high cardiac output and evidence of supernormal myocardial contractility. Conversely, the leftventricular functional response to exercise is inversely related to the degree of hypertrophy. High levels of bloodviscosity, which would tend to blunt the reduction in peripheral resistance expected during sleep or exercise, havealso been associated with left ventricular hypertrophy in patients with essential hypertension. Echocardiographicstudies have provided evidence both for and against the hypothesis that activity of the sympathetic or renin-angiotensin systems plays a direct role in causing hypertensive cardiac hypertrophy. These findings demonstratethe useful role that echocardiographic assessment of left ventricular structure and function may play in hyperten-sion research. (Hypertension 9 [Suppl II]: II-53-II-60, 1987)

KEY WORDS •blood viscosity

echocardiography • hypertension • left ventricular hypertrophy • blood pressure

LEFT ventricular hypertrophy (LVH) plays a dual role inpatients with systemic hypertension — being both a

J necessary adaptation to pump a normal amount ofblood against the increased pressure load and a pathologic mani-festation of hypertensive cardiovascular disease. For manyyears, knowledge of the complex status of the heart in humanhypertension advanced slowly because of the lack of suitablemeans of measuring cardiac anatomy and function in unselectedhypertensive patients or of following their natural history. Thedevelopment over the last decade of accurate echocardiographicmethods for detection of LVH and characterization of ventricu-lar contractile performance has catalyzed an explosion of infor-mation about the heart in hypertension.

From the Department of Medicine, The New York Hospital-CornellMedical Center; the Department of Epidemiology and Social Medicine,Albert Einstein College of Medicine; and the Department of Physiology,Columbia University College of Physicians and Surgeons, New York, NewYork.

Supported in part by Grant HL 18323 from the National Heart, Lung, andBlood Institute.

Address for reprints: Richard B. Devereux, M.D., Division of Cardiolo-gy, Box 222, The New York Hospital-Cornell Medical Center, 525 East68th Street, New York, NY 10021.

In this review, we summarize the available data to providepreliminary answers to the following questions: Do all patientswith systemic hypertension exhibit cardiac involvement? Is hy-pertensive cardiac hypertrophy closely related to the level ofblood pressure, or does it convey independent informationabout disease severity? Are cardiac findings related to cardio-vascular dynamics in patients with hypertension? Do neural orendocrine factors directly influence the heart — beyond theirinfluence on hemodynamics?

Prevalence of Left Ventricular Hypertrophy inHypertension

Detection of LVH by echocardiogram depends not only onthe established accuracy of the method in reflecting anatomicfindings1'2 but also on use of correct normal limits. Althoughconsiderable progress has been made in establishing statisticallyreliable and reproducible normal limits,3' 4 no single criterion isyet completely validated and universally accepted. Despite this,tentative conclusions may be drawn about the prevalence ofLVH among patients with hypertension by examining theresults of studies in which hypertensive patients and normoten-

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FIGURE 1. Prevalence of left ventricular hypertrophy (LVH) infour independent groups of patients with essential hypertension andnormotensive controls.5~s (Reprinted from Devereux el al.'° withpermission.)

sive controls were evaluated by identical echocardiographicmethods.

This approach can be applied in four available clinical studiesof patients with essential hypertension5"8 that include compari-son groups of apparently normal subjects.6"9 In these studies theoverall prevalence of LVH was determined by applying identi-cal cutoffs for left ventricular (LV) mass indexed for body size(e.g., LV mass/body surface area > 120 g/m2) to both patientsand control populations. The prevalence of LVH was 23 to 48%in hypertensive patients and 0 to 10% in normal subjects (Figure1). Overall, 189 of 450 (42%) of hypertensive patients and 9 of251 (3.6%) of controls exhibited LVH (chi square test = 117.1,p< 10"6).10 These data establish that LVH occurs in a substan-tial minority of patients with mild to moderately severe essentialhypertension evaluated in a referral center. The finding thatLVH was detected by echocardiogram in a slightly higher per-centage of apparently normal subjects than had been expectedstatistically for upper 95% confidence limits (3.6% vs 2.5%)may reflect a slight random fluctuation of results in a moderatesized sample or admixture of a few individuals with clinicallyundetected heart disease. A recent study" indicates that theprevalence of LVH by the same echocardiographic criteria issomewhat lower — 17% and 21%, respectively — among unse-lected patients with uncomplicated borderline or establishedhypertension drawn from an employed population.

Further information about the prevalence of LVH in patientswith hypertension has been derived from more recent studies offactors that influence normal LV mass or appear to modify thecardiac response to hypertension. Of greatest importance in thisregard is recognition of demographic variables that should betaken into account in determining statistically valid upper limitsof normal LV mass. All available studies agree that LV massshould be indexed by body size, of which body surface areaappears to be the best measure by a narrow margin.4 Similarly,the three largest echocardiographic studies of normal sub-jects3- *•' have found that LV mass indexed by body surfacearea differs significantly between men and women, and theprimary LV measurements reported by Valdez et al.12. are inaccord with this conclusion. The tentative cutoff values we haveproposed for recognition of LVH, representing the 97th percen-tile of values in apparently normal subjects,4 are 2 111 g/m2 inwomen and a 135 g/m2 in men.

Effect of SexThe prevalence of LVH found in men and women with essen-

tial hypertension is strikingly dependent on whether one usessuch sex-specific criteria or a single criterion of LV mass in-dexed for body surface area. When a single cutoff value forhypertension is applied to both sexes, the prevalence of LVH isconsistently higher among men (26-56%) than women (18-42%) in clinical studies7'l3'14 (Figure 2A). When sex-specificcriteria are used, however, a higher proportion of female(43-61%) than male (18—41%) hypertensive subjects exhibitLVH (Figure 2B). We have recently obtained similar results(i.e., a higher prevalence of LVH in women by sex-specificcriteria and in men by unified criteria) in a study of patients withhypertension in an employed population." The reasons for thisdiscrepancy between men and women with hypertension are notclear but might include either a selective reduction in physicalactivity among men with hypertension or a substantial preva-lence of clinically inapparent heart disease, associated with mildLVH, among apparently normal men. Longitudinal studies ofphysical activity, cardiac status, and cardiovascular morbiditywill be needed to determine the cause.

Influence of RaceNo difference has been detected between normal black and

white subjects in any echocardiographic measurement of LVanatomy or function."' " In contrast, both Dunn etal.16 and ourgroup"' 15 have reported that black patients with essential hy-pertension have a greater degree of LVH than white patientswith similar levels of clinically measured blood pressure, butthis was not found in a previous study.17 Our findings demon-strate a significant increase in relative wall thickness, an indexof concentric LVH, in black patients compared to white patientsof similar age, duration of hypertension, and prior treatmentstatus identified through the same worksite clinics (Table 1). Inthe same group, the greater degree of concentric LVH amongblack patients was associated with a modest elevation of periph-eral resistance (Table 1), whereas white patients from the samepopulation exhibited an increased cardiac output without a sig-nificant increase in peripheral resistance.15 This evidence ofgreater concentric LVH and a hemodynamic pattern felt to char-acterize more advanced hypertension in black as compared towhite patients makes an interesting parallel with the knownhigher incidence of cardiovascular morbidity in black hyperten-sive persons,18 although it has not yet been established whetherthe excess morbidity among blacks is accounted for by thesubset with concentric LVH.

Age and Hypertensive Cardiac HypertrophyBoth increasing age and duration of hypertension would logi-

cally be expected to be associated with a higher prevalence andgreater severity of hypertensive cardiac hypertrophy, but wehave not been able to demonstrate this in cross-sectional studiesof large clinical6'7 or unselected" populations of patients withsystemic hypertension. Evidence does suggest, however, that asmall proportion of elderly hypertensive patients develop severeLVH associated with symptoms of cardiac dysfunction. Topolet al.19 recently reported 21 elderly patients with systemic hy-pertension, predominantly black women, with a mean age of 73years, who exhibited severe concentric LVH, supernormal LVsystolic function, and severely impaired early diastolic LV fill-ing. In an echocardiographic study of the original Framinghamcohort (mean age, 70 ± 7 years), Savage et al.20 found that 27 of1620 (1.7%) exhibited disproportionate thickness of the inter-ventricular septum, associated in nearly all such subjects with ahistory of at least mild hypertension as well as a high prevalenceof heart murmurs and cardiac symptoms. By their design, nei-ther of these reports permits calculation of the prevalence ofcardiac hypertrophy among elderly patients in whom systemic

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FIGURE 2. Prevalence of left ventricular hypertrophy (LVH) in three independent groups of patients with essentialhypertension subdivided by sex.7' '*• '5 A. When the upper limit of normal for both sexes pooled (> 120 glm2) is used,prevalence of LVH is higher in male patients. B. When sex-specific 97thpercentile upper limits of normal are used (males2:135 glm2; females ^110 glm2), the prevalence of LVH is higher in female patients. (Reprinted from Devereux et al.10

with permission.)

hypertension has been diagnosed by conventional clinical crite-ria although the Framingham Study has an optimal data base inwhich to do so.3

Hypertensive Cardiac Hypertrophy and Blood PressureAlthough early studies of highly selected patients suggested

that heart weight was closely related to the level of arterial bloodpressure,21 it is now clear that this is not normally the case. Inseveral groups of patients with uncomplicated essential hyper-tension, physician measurements of systolic blood pressurehave been only weakly related to echocardiographic LV mass,with correlation coefficients of 0.24 to 0.45.7'1322-23 Evenweaker correlations were observed in these studies betweendiastolic arterial pressure and LV mass. A similarly modestrelationship (r = 0.43) was observed by Abi-Samra et al.24 in astudy of 74 patients with systemic hypertension.

Ambulatory Blood PressureTwenty years ago Sokolow et al.25 reported that evidence of

cardiovascular damage in patients with hypertension was moreclosely related to blood pressure measured by a portable record-er than by physicians. More recently, the same group has report-ed that ambulatory blood pressure measurements were betterpredictors than casual determinations of subsequent morbidevents in patients with hypertension.26 Both these studies, how-ever, used an ambulatory recording system that was patient-

activated, thus precluding complete 24-hour recordings, andalso employed indirect means of detecting LVH, such as theelectrocardiogram.

Recording blood pressure through the entire 24-hour periodhas been made possible by development of invasive27 and non-invasive28- M systems with acceptable accuracy. Because oftheir greater acceptability and safety, noninvasive systems havebeen most widely used and have provided important informa-tion about blood pressure variability30 with implications forpatient management.31 Three studies have compared the rela-tionships between echocardiographically determined LV massand physician or 24-hour blood pressure measurement.7'32-33 Ineach study average 24-hour systolic blood pressure was theclosest correlate of LV mass (Table 2). To gain further insightinto the relationship between cardiac hypertrophy and Bloodpressure during normal activity, we categorized.ambulatoryblood pressures by the setting in which they were recorded(e.g., physician's office, occupational workplace, home, andsleep).7 The closest relationships were observed between LVmass index and average workplace systolic blood pressure(r = 0.50, p<0.001) and between end-diastolic relative wallthickness and average workplace diastolic blood pressure (r =0.59, p<0.001). In this study LV mass was less closely relatedto peak blood pressure than to the average workplace bloodpressure. These data suggest that the blood pressure response toregularly recurring stress may have particular importance in thepathogenesis of hypertensive cardiac hypertrophy.

TABLE 1. Cardiac Anatomy and Function in Black and White Normotensive and Hypertensive Subjects

Measurement

Left ventricular mass (g)

Relative wall thickness

Cardiac output (L/min)

Total peripheral resistancex 103 dyncmsec" 3

Blacks(n = 70)

163.2 ±62.6

0.36±0.08

5.63 ±1.91

1.43 ±0.47

Narmotensive

PNS

NS

NS

NS

Whites(n = 62)

163.8±49.2

0.34±0.06

5.93 ±2.05

1.36±0.45

Blacks(n = 30)

207.2±56

0.43 ±0.11

5.80±2.16

1.85±0.72

Hypertensive

P

NS

<0.05

<0.01

<0.01

Whites(n = 45)

203.8 ±76.6

0.37 ±0.07

7 25±2.35

1.42 ±0.46

Data are means ± SD. NS - not significant.Adapted from Hammond et al.13

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11-56 ECHOCARDIOGRAPHY SUPPL II HYPERTENSION, VOL 9, No 2, FEBRUARY 1987

TABLE 2. Correlation Between Blood Pressure Measurements and Left Ventricular Mass

Reference

Devereux et al.7

Kleinert et al.22

Rowlands et al.32

Drayer et al.33

Ren et al.34

n

100

86

50

12

67

Physician

Casual

Systolic

0.24t

0.22

0.45*

0.55

0.16

Diastolic

0.20t

0.07

0.46*

0.10

-0.02

Portable

24-hour

Systolic

0.38

0.26

060*

081*

—

Diastolic

0.31t

0.24

0.35t

0.56

—

recorder

Workplace

Systolic Diastolic

0.50* 0.39*

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Self

Home

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— —

— —

— —

Physician

Exercise

Systolic Diastolic

— —

— —

— —

— —

0 58* 0.05

Data are correlation coefficients between left ventncular mass and the specified type of blood pressure measuring except for the studyof Kleinert et al.20 in which end-diastolic relative wall thickness was the index of left ventncular hypertrophy.

*= p < 0.001; t = p < 0.05; t= p < 0.01. Other correlations are not significant.

Other Blood Pressure MeasurementsBecause obtaining precise 24-hour ambulatory blood pres-

sure recordings is cumbersome and technically difficult, consid-erable attention has been devoted to finding other methods ofobtaining a reliable estimate of patients' average blood pres-sure. Two recent studies have yielded promising results. In thefirst, we22 demonstrated that home blood pressure recordings bytrained patients not only provided a better estimate of average24-hour blood pressure than did physician measurements butalso were more closely correlated to indices of LVH. The sec-ond study, by Ren et al.,34 reported a substantially closer rela-tionship of LV mass to maximum systolic arterial pressure dur-ing treadmill exercise testing than to blood pressure at rest priorto exercise (see Table 2).

Hypertensive Cardiac Hypertrophy and CardiovascularDynamics

Because cardiac hypertrophy is felt to be an important adap-tive response to hypertension, consideration must be given tothe degree to which LVH is matched to the hemodynamic loadand is successful in maintaining cardiac performance in hyper-tension. In the first studies in this regard, performed by Fol-kow35 in experimental animals, the severity of cardiac hyper-tropHy tended to parallel the severity of peripheral vascularresistance. In a subsequent study by Shkhvatsabaya and co-workers,36 echocardiographically determined LV mass correlat-ed significantly (r = 0.60, p<0.001) with vascular resistancein the calf, measured by plethysmography during maximalvasodilation.

Extending this line of investigation to 100 patients with es-sential hypertension, we examined the relationships betweensystemic hemodynamics and the pattern of LV anatomy.13 Asignificant positive correlation (r = 0.52, p<0.001) was ob-served between total peripheral resistance and end-diastolic LVrelative wall thickness (Figure 3A). Furthermore, cardiac indexwas inversely related to relative wall thickness (r = —0.47,p < 0.001) (Figure 3B). Taken together, these experimental andclinical studies suggest that the cardiac pattern of concentricLVH and the hemodynamic pattern of elevated peripheral resis-tance with low cardiac output are pathophysiologically interre-lated.

Left Ventricular PerformanceTo investigate further the relationships between cardiac struc-

ture and function, we have performed an additional series ofstudies. In order to exclude the possibility that excessive orinadequate degrees of LVH in relation to blood pressure loadaccounted for differences in LV function, we measured myocar-dial afterload by calculating end-systolic LV wall stress with acatheterization-validated formula.37 As predicted from basicprinciples of cardiac mechanics, a close inverse relationship

existed in 87 normotensive subjects between end-systolic stressand LV fractional shortening, an echocardiographic index ofsystolic ventricular performance (r = -0.83, /?<0.OOOl).38 Asignificant inverse relationship between these variables was alsoobserved in 81 unmedicated patients with essential hypertension(r = -0.78, p<0.001). When the data points from the hyper-tensive patients were superimposed on 95% confidence limitsderived from the normal subjects (Figure 4), a significant pro-portion of the hypertensive patients exhibited high fractionalshortening in relationship to wall stress (19 of 81 or 23%;/><0.001 vs 1 of 87 normotensive subjects).

Subdivision of hypertensive patients into groups with normaland increased LV performance based on this analysis of cardiacmechanics revealed striking differences in both systemic hemo-dynamics and LVH (Table 3). Of note, the patients with in-creased ventricular performance exhibited substantially in-creased cardiac output, lower peripheral resistance, and anabsence of LVH compared to the hypertensive patients withnormal ventricular performance. In a more recent study fromour laboratory, hypertensive patients who had high fractionalshortening in relation to end-systolic stress on baseline measure-ments exhibited a significantly higher (p< 0.005) slope of theend-systolic force-length line during nitroglycerin-induced re-duction in hemodynamic load than hypertensive patients whofell into the normal range of fractional shortening in relation toend-systolic stress.39 Taken together, these studies suggest thatin the majority of mildly hypertensive patients the heart plays asecondary role, undergoing adaptive hypertrophy in proportionto the elevation of blood pressure. In a significant minority ofsuch patients, however, increased myocardial contractility mayhave pathogenetic importance by allowing the heart to pump anincreased cardiac output without need for any hypertrophy.

Since an important capacity of the normal heart is the abilityto sustain a strikingly increased hemodynamic load during nor-mal activity, assessment of the heart in hypertension is notcomplete without evaluation of the cardiac responses to exer-cise. This has been directly evaluated by means of radionuclidecineangiography at rest and during exercise in several recentstudies.40' 41 Among hypertensive patients with no evidence ofcoronary artery disease, the prevalence of abnormal LV ejectionfraction responses to exercise has ranged from 9 of 37 patients(24%)42 to 15 of 20 patients (75%).43 Our studies40'4I indicatethat a small proportion — approximately 10% — of the hyper-tensive patients who exhibit abnormal LV functional reservecan be identified by evidence of impaired myocardial contractil-ity (low echocardiographic fractional shortening in relation toend-systolic stress) at rest; whereas in the remainder, LV dys-function is only revealed by imposition of exercise stress. Apreliminary study from our laboratory44 suggests that LV dys-function during exercise and LVH are closely linked, with aninverse linear relationship (r = -0.50, p<0.0\) between echo-

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(end-diastole)

FIGURE 3. A. Left ventricular (LV) relative wall thickness at end diastole (vertical axis) is directly related to totalperipheral resistance (horizontal axis) in 100 unmedicated patients. B. Cardiac index (vertical axis) is inversely relatedto LV relative wall thickness at end diastole (horizontal axis). (Reprinted from Devereux et al.'3 with permission.)

cardiographically determined LV muscle mass and the changein LV ejection fraction from rest to exercise observed amonghypertensive patients with LVH.

The ability of the left ventricle to sustain a normal or in-creased workload is also dependent on its diastolic performancecharacteristics. Abnormalities of LV diastolic time intervals andfilling rates have been well documented in patients with system-ic hypertension45' ** and may be a more sensitive marker ofhypertensive cardiac involvement than echocardiographicLVH.47 These diastolic abnormalities appear to be manifesta-tions of so-called pathologic LVH since subjects with a similardegree of exercise-induced physiologic hypertrophy exhibitednormal LV diastolic properties in one study.48

40 60 SO DO

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FIGURE 4. Data points for left ventricular fractional shorteningand end-systolic stress in 81 untreated patients with essential hy-pertension are superimposed on the solid regression line anddashed 95% confidence interval of this relationship in 87 normalsubjecfs. A close inverse relation is observed (T = —0.78, p<0.001), and 19 of 81 hypertensive patients exhibit increased ven-tricular function in relation to wall stress (compared to 1 of 87normotensive subjects, p<0.0001). (Reprintedfrom Lulas et al.3S

with permission of the American Heart Association.)

Blood ViscositySeveral lines of evidence suggest that altered blood rheology

may be importantly related to cardiac findings in hypertension.Hematocrit and blood viscosity have been found to be higher inhypertensive than normotensive individuals.49' w Recently wereported a modest direct relationship between blood pressureand whole blood viscosity in both hypertensive and normoten-sive subjects." We found that increased whole blood viscosityin unselected patients with mild essential hypertension account-ed for the entire increase in peripheral resistance in them ascompared with normotensive subjects drawn from the sameemployed population.52 Finally, high rates of cardiovascularmorbidity have been reported in patients with hyperviscositydue to hypertension53 or so-called pseudo-polycythemia.54 Nostudy, however, had related blood viscosity to objective cardiacmeasurements in patients with hypertension.

Therefore, we recently undertook a study to examine therelationships among arterial blood pressure, whole blood vis-cosity, and LVH in 24 patients with essential hypertension and13 age- and sex-matched control subjects.23 A significant corre-lation was observed between mean arterial blood pressure andwhole blood viscosity in this study population (r = 0.52,p<0.005). Similarly, mean blood pressure was modestly relat-ed to LV mass in the hypertensive patients (r = 0.47, p<0.02)and in the normotensive subjects (r = 0.44, p = NS; Figure

TABLE 3. Hemodynamics and Left Ventricular Hypertrophy in Hypcrten-sive Patients with Normal and Increased Left Ventricular Performance

Patients Patientswith with

normal LV increased LVVariable performance p performance

Age (yr)

Mean blood pressure (mm Hg)

Cardiac index (L/min/m2)

Total peripheral resistance(dyncmsec"5)

Relative wall thickness

53±9

111±13

3.39±1.00

1,582 ±584

0 42±0.10

NS

NS

<0.005

<0.05

<0.005

55 + 13

112±15

4.25±1.33

l,257±5O2

0.34±0.06

LV = left ventricular, NS = not significant.Adapted from Lutas et al.3*

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FIGURE 5. A. Mean blood pressure and left ventricular (LV) mass in patients with essential hypertension (r = 0.47,p < 0.02) and in normotensive control subjects (r = 0.44, NS). B. Relationship between blood viscosity at a shear rate of104 sec'1 (T\B 104) and LV mass. A close relation exists between these variables in the hypertensive patients (r = 0.80,p < 0.001), and the points for hypertensive patients without LV hypertrophy (below dotted line) tend to overlap those ofthe normotensive control subjects. (Reprinted from Devereux et al.23 with permission.)

5A). A close correlation was observed (Figure 5B) betweenwhole blood viscosity at the high shear rate of 104 sec ~' and LVmass in the hypertensive patients (r = 0.80, p< 0.001), whichwas significantly closer than the correlation between meanblood pressure and LV mass (p<0.02). Furthermore, as shownin Figure 5B, the relationship between viscosity and LV mass innormotensive subjects closely resembled that in the hyperten-sive patients with normal whole blood viscosity.

Neurohumoral Factors and Hypertensive CardiacHypertrophy

Although hemodynamic factors have received the most atten-tion in studies of the pathogenesis of hypertensive cardiac hy-pertrophy, considerable scatter clearly exists in the relationshipsbetween the best available measures of blood pressure and LVmuscle mass. The search for nonhemodynamic causes of LVHin hypertensive patients has focused mostly on neurohumoralfactors, principally the sympathetic and renin-angiotensinsystems.

Evidence in favor of the so-called catecholamine hypothesisof LVH was originally derived from studies using sympatheticagonists33 and antagonists56 in intact animals. More recently,Simpson and co-workers37' 38 have provided evidence that in-duction of protein synthesis by norepinephrine in tissue-cul-tured cardiac myocytes is an a,-receptor-mediated phenom-enon. Limited studies in patients with essential hypertensionhave suggested a positive relationship between plasma norepi-nephrine concentration and LV mass59 and a greater reduction inLV mass than blood pressure during treatment with sympatho-lytic drugs.60'6I These results have not been consistently ob-served,62 however, and recent observations in patients withpheochromocytoma63 suggest that applicability of the catechol-amine hypothesis to clinical hypertension may be limited.

The suggestion that renin-angiotensin system activity direct-ly stimulates myocardial hypertrophy is also based primarily onexperimental observations. Thus, Robertson et al.6* reportedthat radiolabeled angiotensin II rapidly localized in nuclei ofcardiac and smooth muscle cells, while Khairallah and Kana-bus65 have documented a significant increase in ventricularweight after 6 days of angiotensin II infusion at a mildly pressordose. Some studies of patients treated with angiotensin convert-ing enzyme inhibitors have suggested that echocardiographic

LV mass may decrease more than expected for the inducedreduction in blood pressure,6* but this finding has not beenconsistent.67' M

Our studies suggest that the renin-angiotensin system mayhave more important effects on LV function than on its struc-ture. Thus, patients with low-renin essential hypertension hadhigher LV fractional shortening and cardiac index than those innormal and high-renin subgroups,6 while relief of vasoconstric-tion by captopril in those with high-renin essential hypertensionwas associated with an increase in cardiac index.68 In a separatestudy,69 we observed an inverse relation between plasma reninactivity and LV fractional shortening, an index of systolic per-formance. We have subsequently documented that patients withrenovascular hypertension, the overwhelming majority ofwhom have high plasma renin levels, have significantly poorerLV systolic function than age-, sex- and blood pressure-matched patients with essential hypertension.70

AcknowledgmentWe thank Miss Virginia Bums for her assistance in preparation of this

manuscript.

References1. Devereux RB, Reichek N. Echocardiographic determination of left ven-

tricular mass in man: anatomic validation of the method. Circulation1977^5:613-618

2. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assess-ment of left ventricular hypertrophy: comparison to necropsy findings.Am J Cardiol 1986^7.450-458

3. Savage DD, Abbott RD, Padgett S, Anderson SJ, Garrison RJ. Epide-miologic features of left ventricular hypertrophy in normotensive andhypertensive subjects. In: ter Keurs HEDJ, Schipperheyn JJ, eds. Cardi-ac left ventricular hypertrophy. The Hague: Martinus Nijhoff, 1983:2—15

4. Devereux RB, Lutas EM, CasalePN.etal. Standardization of M-modeechocardiographic left ventricular anatomic measurements. J Am CollCardiol 1984;4:1222-1230

5. Savage DD, Drayer JIM, Henry WL, et al. Echocardiographic assess-ment of cardiac anatomy and function in hypertensive patients. Circula-tion 1979^9:623-632

6. Devereux RB, Savage DD, Drayer JIM, Laragh JH. Left ventricularhypertrophy and function in high, normal, and low-renin forms of es-sential hypertension. Hypertension 1982;4:524-531

7. Devereux RB, Pickering TG, Harshfield GA, et al. Left ventricularhypertrophy in patients with hypertension: importance of blood pressureresponse to regularly recurring stress. Circulation 1983;68:470—476

8. Reichek N, Devereux RB. Reliable estimation of peak left ventricular

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systolic pressure by M-mode echographic determined end-diastolic rela-tive wall thickness: identification of severe aortic stenosis in adult pa-tients. Am Heart J 1982; 103:202-209

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R B Devereux, T G Pickering, M H Alderman, S Chien, J S Borer and J H Laraghpathophysiologic variables.

Left ventricular hypertrophy in hypertension. Prevalence and relationship to

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