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Original Investigation |

Reduction of Left Ventricular Hypertrophy After Exercise and Weight Loss in Overweight Patients With Mild Hypertension FREE

Alan Hinderliter, MD; Andrew Sherwood, PhD; Elizabeth C. D. Gullette, PhD; Michael Babyak, PhD; Robert Waugh, MD; Anastasia Georgiades, PhD; James A. Blumenthal, PhD
[+] Author Affiliations

From the Department of Medicine, University of North Carolina, Chapel Hill (Dr Hinderliter), and the Departments of Psychiatry and Behavioral Sciences (Drs Sherwood, Gullette, Babyak, Georgiades, and Blumenthal) and Medicine (Dr Waugh), Duke University Medical Center, Durham, NC.


Arch Intern Med. 2002;162(12):1333-1339. doi:10.1001/archinte.162.12.1333.
Text Size: A A A
Published online

Background  Hypertrophy and concentric remodeling of the left ventricle are important manifestations of hypertension that are associated with increased morbidity and mortality. Although lifestyle interventions are efficacious in lowering blood pressure, evidence that they have a beneficial effect on target organs has been lacking.

Objective  To assess the effects of regular aerobic exercise or exercise plus weight management counseling on left ventricular mass and geometry in overweight, sedentary men and women with high-normal or mildly elevated blood pressure.

Methods  Eighty-two participants in a randomized, controlled trial were assigned to supervised aerobic exercise only, a behavioral weight management program that included exercise, or a waiting-list control group for 6 months. Blood pressure and echocardiographic measures of left ventricular structure were measured at baseline and at the conclusion of the treatment phase.

Results  The 45 women and 37 men had a mean ± SD age of 47 ± 9 years and had a mean ± SD blood pressure of 140 ± 10/93 ± 5 mm Hg. Blood pressure fell by 7/6 mm Hg in the weight management group and by 3/4 mm Hg in the aerobic exercise group. In association with these decreases in blood pressure, participants in the intervention groups exhibited significant decreases in left ventricular relative wall thickness (P = .003), posterior wall thickness (P = .05), and septal thickness (P = .004) and a trend toward a decrease in indexed left ventricular mass (P = .08) relative to the control group.

Conclusions  In a cohort of overweight, sedentary men and women, exercise and weight loss reduced blood pressure and induced favorable changes in left ventricular structure.

Figures in this Article

HYPERTROPHY and concentric remodeling of the left ventricle are important manifestations of hypertension that are associated with an enhanced risk for morbidity and mortality. In the general population and in cohorts with hypertension or coronary artery disease, increased left ventricular mass is a predictor of cardiovascular events independent of blood pressure or other traditional risk factors.14 The geometric pattern of hypertrophy is also of prognostic importance. Patients with concentric remodeling, ie, an increase in the ratio of wall thickness to chamber dimension but normal left ventricular mass, have a cardiovascular risk intermediate between those with normal left ventricular structure and those with concentric hypertrophy.5,6 Regression of hypertrophy is associated with a reduction in cardiovascular risk.79

A number of studies have demonstrated that lowering blood pressure with medication results in regression of left ventricular hypertrophy.10,11 Although lifestyle modifications such as regular aerobic exercise are viewed as important elements of antihypertensive therapy in patients with high-normal or mildly elevated blood pressure,12,13 the effects of nonpharmacologic measures on left ventricular mass and structure have not been extensively evaluated. Kokkinos et al14 demonstrated significant blood pressure reduction and regression of left ventricular hypertrophy in severely hypertensive African Americans who engaged in moderately intense aerobic exercise training. However, several smaller studies in patients with milder hypertension have yielded conflicting results.1518 Published reports have not consistently demonstrated a beneficial effect of weight loss or of weight loss combined with exercise on left ventricular structure.15,1923

A randomized, controlled trial recently reported by our group demonstrated that exercise training is effective in lowering blood pressure in overweight, sedentary patients with high-normal or mildly elevated blood pressure, and that weight loss is of added benefit when combined with aerobic training.24 To assess the effect of these lifestyle modifications on ventricular hypertrophy, we examined echocardiographic measures of left ventricular structure in a substudy of this trial.

SUBJECTS

Participants were aged at least 29 years and were generally healthy, with no history of cardiac disease, renal insufficiency, or diabetes mellitus and no evidence of secondary hypertension. None had been treated with antihypertensives for at least 6 weeks. Inclusion criterion consisted of a casual systolic blood pressure of 130 to 180 mm Hg and/or diastolic blood pressure of 85 to 110 mm Hg, determined by averaging blood pressure measurements from 4 separate visits during a 3-week period. All subjects were overweight or obese (body mass index [BMI], 25-37) and sedentary (not performing regular aerobic exercise). None were treated with medications that have hemodynamic effects, and none had a history of abuse of alcohol or other drugs.

PROTOCOL

Details of the study protocol have been described previously.24 The protocol was approved by the institutional review board at Duke University Medical Center, Durham, NC, and informed consent was obtained from each subject before participation.

Subject eligibility for the study was established during a series of screening visits that included a history and physical examination, measurement of height and weight, determination of baseline casual blood pressure, and assessment of dietary content. Exercise capacity was determined by treadmill exercising testing, and left ventricular geometry and mass were measured by echocardiography. Participants were than randomized in a 2:2:1 ratio, by sex, to 1 of the following 6-month treatment conditions: (1) exercise, (2) exercise plus a behavioral weight loss program, or (3) waiting-list control. In addition, 5 subjects who met all eligibility criteria but were unable to commit to regular participation in the supervised exercise sessions were included in the control group. At the conclusion of treatment, measurements of weight, blood pressure, dietary content, exercise capacity, and left ventricular structure were repeated.

MEASUREMENTS
Blood Pressure

Blood pressure was measured by a trained technician using a random-zero sphygmomanometer. On each visit, blood pressure was measured 4 times at 2-minute intervals after an initial 5-minute rest. The last 3 measurements were averaged to represent the blood pressure value for that visit, and the values for each of 4 visits during a 3-week period were averaged to determine the casual blood pressure. Blood pressure determinations were made in this standardized manner at baseline and after the 6-month intervention.

Body Weight

Weight was measured in kilograms using a standard-balance scale, and height was measured in meters. Body mass index was calculated as weight in kilograms divided by the square of height in meters.

Exercise Capacity

Exercise capacity was assessed by measuring maximum oxygen consumption using the Duke–Wake Forest Protocol.25 This protocol begins at 3.2 km/h (2.0 mph) and 0% grade, and the workload is increased at a rate of 1 metabolic equivalent per minute. Expired gases were collected for the determination of peak oxygen consumption using a metabolic cart.

Dietary Content

Subjects recorded all food intake for 4 consecutive days in a diet diary that was analyzed for energy and nutritional content.

Echocardiography

Echocardiography was performed with the use of an imaging system (Hewlett-Packard, Palo Alto, Calif) equipped with a 2.5-MHz phased-array transducer. Images were obtained with the patient in the partial left lateral decubitus position, and were recorded on a Super-VHS videotape. The studies were subsequently quantified by one of us (A.H.), who was masked to the subjects' identifying information. Left ventricular end-diastolic diameter, posterior wall thickness, and interventricular septal thickness were measured just distal to the mitral valve tips at end diastole, using a leading edge–to–leading edge convention. Left ventricular mass was estimated using a cube function model with a correction factor.26 Relative wall thickness, a measure of the ratio of the left ventricular wall thickness to the chamber diameter, was calculated as the sum of the posterior wall thickness and the interventricular septal thickness divided by the left ventricular end-diastolic diameter. To adjust for variations in heart size due to differences in body size, indexed left ventricular mass was calculated as ventricular mass (in grams) divided by height (meters)2.7 (g/m2.7), as described by de Simone et al.27

INTERVENTIONS
Exercise

Subjects in this group participated in supervised exercise sessions 3 to 4 times per week for 6 months. The exercise protocol consisted of 10 minutes of warm-up exercise; 35 minutes of bicycle ergometry, walking, or jogging on a track to achieve a heart rate between 75% and 85% of the maximal heart rate reserve; and 10 minutes of cool-down exercise. All training sessions were supervised by an exercise physiologist, who monitored the heart rates of each participant several times per session. Subjects in this treatment group were instructed to maintain their usual diets.

Weight Management

Subjects randomized to this intervention exercised 3 to 4 times weekly as described in the previous paragraph. In addition, they participated in a behavioral modification program designed to facilitate weight loss. This program consisted of 26 weekly group sessions. Sessions were based on the LEARN program,28 which focuses on the following 5 elements: lifestyle, exercise, attitudes, relationships, and nutrition. Topics of discussion included distinguishing cravings from hunger, planning healthy meals, shopping for food, dealing with pressure to eat, eating away from home, and coping with relapse. The primary goal of the intervention was a weight loss of 0.5 to 1.0 kg/wk achieved by decreasing energy and fat intake through permanent lifestyle changes. Initial dietary goals consisted of an energy intake of approximately 1200 calories for women and 1500 calories for men, with 15% to 20% of this energy from fat.

Waiting-List Control

Subjects in the waiting-list control group were contacted monthly and encouraged to maintain their usual dietary and exercise habits until the second evaluation after 6 months of observation. They were then offered the opportunity to participate in either of the active treatment groups.

ANALYSIS OF DATA

Descriptive statistics of the study cohort and the participants in each intervention were expressed as mean ± SD. We assessed baseline differences among treatment groups using 1-way analysis of variance for continuous variables and χ2 tests for categorical variables. We evaluated the treatment effects on weight, exercise duration, blood pressure, and left ventricular dimensions using a general linear model, with the posttreatment value for the measurement of interest serving as the dependent variable and treatment group and baseline values for the measurement of interest serving as independent variables. Because controlling for baseline values of the outcome variables of interest has the effect of producing residualized change scores, the present analyses can be interpreted as testing treatment group differences on the change in outcome variables. Orthogonal contrasts were estimated by comparing the weight management group with the exercise group and the combined treatment groups with the control group. Tests for homogeneity of slopes (treatment group × sex and treatment group × race) were conducted to exclude an influence of sex or race on the treatment effects on measures of left ventricular structure.

Echocardiograms of high technical quality were obtained before and after treatment in 82 subjects. Of the 144 subjects originally enrolled, 4 (3%) did not have baseline echocardiograms; 16 (11%) did not return for a follow-up study; and 42 (29%) had studies in which left ventricular dimensions or wall thicknesses could not be quantified with confidence. The subjects with interpretable ultrasound studies tended to weigh less (91.7 ± 16.8 vs 97.6 ± 13.9 kg; P = .03) and have a lower BMI (31.4 ± 4.1 vs 34.2 ± 3.9; P<.001) than those with unsatisfactory images; no differences were seen in age, sex, race, or baseline clinic blood pressure. The results described in this manuscript refer to the 82 subjects for whom complete echocardiographic data were available.

Characteristics of the study population and subjects in each intervention group are noted in Table 1. The 3 groups were comparable in all baseline clinical and demographic characteristics except that the control group had more nonwhite subjects than the active treatment groups (P = .03).

Table Graphic Jump LocationTable 1. Baseline Characteristics of the Study Population by Intervention Group*

Echocardiographic characteristics of subjects in the 3 groups are shown in Table 2. For the study group as a whole, 25 participants (30%) had left ventricular hypertrophy, defined as a left ventricular mass index exceeding the 95th percentile for a lean, normotensive reference population previously studied in our laboratory (>53.9 g/m2.7). An additional 11 (13%) had concentric left ventricular remodeling (ie, an increased relative wall thickness [>0.51] but normal left ventricular mass). Participants in the 3 treatment groups were similar in each measure of left ventricular structure.

Table Graphic Jump LocationTable 2. Baseline Echocardiographic Characteristics of the Study Population by Intervention Group*

At the conclusion of the intervention phase of the study, subjects in the weight management group consumed less energy than those in the exercise and control groups (P<.001). The decrease in daily energy intake from baseline averaged 717 calories in the weight management group but only 120 and 109 calories in the exercise and control groups, respectively. Similarly, those in the weight management group consumed less sodium after the intervention (P<.001), averaging a decrease of 1094 mg/d, compared with decreases of 568 mg/d in the exercise group and 217 mg/d in the control group. No significant differences were found between groups in the consumption of potassium, calcium, or magnesium.

Figure 1 illustrates posttreatment values for weight, BMI, peak oxygen consumption, and blood pressure, corrected for baseline values, for subjects in each of the 3 groups. Significant group differences were seen in postintervention weight and BMI (P<.001 for the exercise group vs the weight management group; P<.001 for both active treatment groups vs the control group). Participants in the weight management group exhibited an average weight loss of 7.4 kg, compared with a loss of 2.3 kg in the exercise group and a gain of 0.2 kg in the control group. Both interventions also resulted in improved exercise capacity, as demonstrated by increases in peak oxygen consumption (P<.001 for the active treatment groups vs the control group). Adjusted posttreatment diastolic blood pressure was significantly lower (P<.001), and posttreatment systolic blood pressure was marginally lower (P = .09) in the active treatment groups relative to the control group. The average reductions in blood presssure were 6.8/5.9 mm Hg and 3.2/4.4 mm Hg in the weight management and exercise groups, respectively, compared with an increase of 0.1/0.8 mm Hg in the control group.

Place holder to copy figure label and caption
Figure 1.

Weight, body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), peak oxygen consumption, and blood pressure (BP) after treatment, adjusted for pretreatment levels. CT indicates waiting-list control group; EX, exercise group; WM, weight management group; asterisk, a significant difference between the combined WM and EX groups and the CT group (P<.05); and dagger, a significant difference between the WM and EX groups (P<.05).

Graphic Jump Location

The effects of the interventions on echocardiographic variables are shown in Figure 2. Relative to the control group, subjects in the active intervention groups had significantly smaller adjusted posttreatment posterior wall (P = .05) and septal (P = .004) thicknesses and a nonsignificant trend toward a greater end-diastolic diameter. Subjects in the weight management group exhibited 5% decreases in posterior wall and septal thicknesses and a 3% increase in end-diastolic diameter. Those in the exercise group had similar changes, with a 3% decrease in posterior wall thickness, a 5% decrease in septal thickness, and a 2% increase in left ventricular chamber dimension. No significant changes in these dimensions were noted in the control group. In part due to the increase in chamber size associated with exercise training, the adjusted decrease in left ventricular mass index in the intervention groups was modest and not statistically significant (P = .08). However, subjects in the active treatment groups had a significantly smaller adjusted posttreatment relative wall thickness compared with those in the control group (P = .003). During the intervention, relative wall thickness decreased by 7% in the weight management group and by 6% in the exercise group. This decrease in relative wall thickness in the intervention groups remained significant when analyses controlled for baseline differences in race (P = .01) and when the 5 nonrandomized controls were excluded (P = .04). No significant interactions were noted between treatment group and race or sex for any of the measures of left ventricular structure.

Place holder to copy figure label and caption
Figure 2.

Echocardiographic variables after treatment, adjusted for pretreatment values. LV indicates left ventricular; asterisk, significant difference between the combined WM and EX groups and the CT group (P<.05). Other abbreviations are described in the legend to Figure 1.

Graphic Jump Location

In our study of overweight, sedentary subjects with high-normal or mildly elevated blood pressure, lifestyle interventions consisting of regular aerobic exercise and weight management counseling resulted in improved exercise capacity, weight loss, and decreases in blood pressure that were associated with ventricular remodeling. Regular aerobic exercise with or without weight loss led to decreases in posterior wall and septal thicknesses, a decrease in relative wall thickness, and a trend toward a decrease in indexed left ventricular mass, independent of sex or race.

LEFT VENTRICULAR ADAPTATIONS TO EXERCISE AND WEIGHT LOSS

Aerobic conditioning in normotensive individuals is associated with an increase in the end-diastolic dimension of the left ventricle and a proportionate increase in wall thickness.29 These adaptations to exercise develop rapidly, with significant changes in left ventricular architecture detectable by echocardiography within weeks of the initiation of training.30 Cross-sectional studies document that obesity is associated with eccentric hypertrophy, an increase in left ventricular chamber size and wall thickness, at all levels of blood pressure.3133 Most weight reduction intervention trials that have used echocardiography have found that weight loss leads to a decrease in left ventricular wall thickness but has little effect on chamber size.19,20

EXERCISE AND WEIGHT LOSS INTERVENTIONS IN HYPERTENSION

Few studies have evaluated the effects of lifestyle modifications on left ventricular structure in patients with hypertension. Kokkinos et al14 described the changes in left ventricular mass and architecture observed in severely hypertensive, medically treated African American men who completed a 12-week program of moderately intensive exercise. Subjects participating in the exercise intervention exhibited a decrease in diastolic blood pressure from 89 to 84 mm Hg, accompanied by decreases in left ventricular mass and wall thickness but no significant change in end-diastolic diameter. Previous studies in patients with mild hypertension have examined smaller numbers of patients and have generally not included randomized control groups. Reid et al15 described the effects of 12 weeks of exercise, weight loss, or both in 23 obese individuals with a mean baseline blood pressure of 131/84 mm Hg. Exercise and weight loss resulted in significant blood pressure reduction, and the effects of these interventions were additive. No significant changes were noted in left ventricular mass or dimensions, however. Baglivo et al17 demonstrated a decrease in blood pressure in 25 middle-aged hypertensive subjects after endurance exercise training, with a marginally significant decrease in left ventricular mass. Eleven older adults with mild to moderate hypertension were studied by Turner et al.18 After 7 months of regular aerobic exercise, resting systolic blood pressure, left ventricular wall thickness, and the wall thickness-radius ratio were significantly decreased. Finally, Zanettini et al16 described reductions in left ventricular mass and wall thickness, with no significant change in chamber diameter, in an uncontrolled trial of aerobic exercise in 14 patients with mildly elevated diastolic blood pressure.

In our study, significant blood pressure reductions were observed in both active intervention groups, but the amount of weight loss and the magnitude of blood pressure lowering were greater in those who received weight management counseling in addition to exercise training. Subjects in the 2 groups exhibited similar changes in left ventricular structure, however. This observation suggests that, in a relatively short 6-month intervention, exercise has a greater influence on left ventricular architecture than does weight loss. Additional research will be required to determine whether weight loss sustained over a longer period results in incremental changes in left ventricular wall thickness and mass.

CLINICAL SIGNIFICANCE OF THE FINDINGS

Previous observational studies using echocardiography have demonstrated that left ventricular hypertrophy and remodeling are predictors of cardiovascular morbidity and mortality, independent of blood pressure and other traditional risk factors.1,6 More recent data suggest that favorable changes in left ventricular structure are associated with a reduction in risk.7,9 Lifestyle interventions such as regular aerobic exercise and weight loss are recommended as initial therapy in overweight patients with high-normal or mildly elevated blood pressure. Although a number of studies have suggested that these interventions are efficacious in reducing blood pressure, evidence that they minimize end-organ damage or prevent cardiovascular events has been lacking. Our study demonstrates that these nonpharmacologic measures not only reduce blood pressure but also induce favorable changes in left ventricular structure. These findings support a strategy of lifestyle modification as an initial approach in the management of overweight, sedentary patients with high-normal or mildly elevated blood pressure.

Accepted for publication October 22, 2001.

This study was supported by grants HL 49572 and HL 59672 from the National Institutes of Health, Bethesda, Md; and grant M01-RR-30 from the General Clinical Research Center Program, National Center for Research Resources, National Institutes of Health.

We thank Anne Middleton for her contribution in the preparation of the manuscript.

Corresponding author and reprints: Alan L. Hinderliter, MD, Division of Cardiology, University of North Carolina, CB 7075, 338 Burnett-Womack, Chapel Hill, NC 27599-7075 (e-mail: hinderli@med.unc.edu).

Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med. 1989;110101- 107
Link to Article
Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;3221561- 1566
Link to Article
Casale  PNDevereux  RBMilner  M  et al.  Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med. 1986;105173- 178
Link to Article
Liao  YCooper  RSMcGee  DLMensah  GAGhali  JK The relative effects of left ventricular hypertrophy, coronary artery disease, and ventricular dysfunction on survival among black adults. JAMA. 1995;2731592- 1597
Link to Article
Koren  MJDevereux  RBCasale  PNSavage  DDLaragh  JH Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114345- 352
Link to Article
Verdecchia  PSchillaci  GBorgioni  C  et al.  Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass. J Am Coll Cardiol. 1995;25871- 878
Link to Article
Yurenev  APDyakonova  HGNovikov  ID  et al.  Management of essential hypertension in patients with different degrees of left ventricular hypertrophy: multicenter trial. Am J Hypertens. 1992;5 (suppl) 182S- 189S
Levy  DSalomon  MD'Agostino  RBBelanger  AJKannel  WB Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation. 1994;901786- 1793
Link to Article
Muiesan  MLSalvetti  MRizzoni  DCastellano  MDonato  FAgabiti-Rosei  E Association of change in left ventricular mass with prognosis during long-term antihypertensive treatment. J Hypertens. 1995;131091- 1105
Link to Article
Gottdiener  JSReda  DJMassie  BMMaterson  BJWilliams  DWAnderson  RJfor the VA Cooperative Study Group on Antihypertensive Agents, Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. Circulation. 1997;952007- 2014
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Schmieder  REMartus  PKlingbeil  A Reversal of left ventricular hypertrophy in essential hypertension: meta-analysis of randomized double-blind studies. JAMA. 1996;2751507- 1513
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Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, The Sixth Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med. 1997;1572413- 2446
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Guidelines Subcommittee of the World Health Organization, International Society of Hypertension (WHO-ISH), 1999 World Health Organization–International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens. 1999;17151- 183
Kokkinos  PFNarayan  PColleran  JAPittares  ANotargiacomo  AReda  D Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension. N Engl J Med. 1995;3331462- 1467
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Blumenthal  JASherwood  AGullette  ECD  et al.  Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med. 2000;1601947- 1958
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Figures

Place holder to copy figure label and caption
Figure 1.

Weight, body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), peak oxygen consumption, and blood pressure (BP) after treatment, adjusted for pretreatment levels. CT indicates waiting-list control group; EX, exercise group; WM, weight management group; asterisk, a significant difference between the combined WM and EX groups and the CT group (P<.05); and dagger, a significant difference between the WM and EX groups (P<.05).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Echocardiographic variables after treatment, adjusted for pretreatment values. LV indicates left ventricular; asterisk, significant difference between the combined WM and EX groups and the CT group (P<.05). Other abbreviations are described in the legend to Figure 1.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Baseline Characteristics of the Study Population by Intervention Group*
Table Graphic Jump LocationTable 2. Baseline Echocardiographic Characteristics of the Study Population by Intervention Group*

References

Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med. 1989;110101- 107
Link to Article
Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;3221561- 1566
Link to Article
Casale  PNDevereux  RBMilner  M  et al.  Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med. 1986;105173- 178
Link to Article
Liao  YCooper  RSMcGee  DLMensah  GAGhali  JK The relative effects of left ventricular hypertrophy, coronary artery disease, and ventricular dysfunction on survival among black adults. JAMA. 1995;2731592- 1597
Link to Article
Koren  MJDevereux  RBCasale  PNSavage  DDLaragh  JH Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114345- 352
Link to Article
Verdecchia  PSchillaci  GBorgioni  C  et al.  Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass. J Am Coll Cardiol. 1995;25871- 878
Link to Article
Yurenev  APDyakonova  HGNovikov  ID  et al.  Management of essential hypertension in patients with different degrees of left ventricular hypertrophy: multicenter trial. Am J Hypertens. 1992;5 (suppl) 182S- 189S
Levy  DSalomon  MD'Agostino  RBBelanger  AJKannel  WB Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation. 1994;901786- 1793
Link to Article
Muiesan  MLSalvetti  MRizzoni  DCastellano  MDonato  FAgabiti-Rosei  E Association of change in left ventricular mass with prognosis during long-term antihypertensive treatment. J Hypertens. 1995;131091- 1105
Link to Article
Gottdiener  JSReda  DJMassie  BMMaterson  BJWilliams  DWAnderson  RJfor the VA Cooperative Study Group on Antihypertensive Agents, Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. Circulation. 1997;952007- 2014
Link to Article
Schmieder  REMartus  PKlingbeil  A Reversal of left ventricular hypertrophy in essential hypertension: meta-analysis of randomized double-blind studies. JAMA. 1996;2751507- 1513
Link to Article
Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, The Sixth Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med. 1997;1572413- 2446
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Guidelines Subcommittee of the World Health Organization, International Society of Hypertension (WHO-ISH), 1999 World Health Organization–International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens. 1999;17151- 183
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