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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Am J Med. Author manuscript; available in PMC Oct 1, 2009.
Published in final edited form as:
PMCID: PMC2574427
NIHMSID: NIHMS74464

Left Ventricular Hypertrophy and Cardiovascular Mortality by Race and Ethnicity

Abstract

Background

Left ventricular hypertrophy is a major independent risk factor for cardiovascular mortality. The contribution of left ventricular hypertrophy to racial and ethnic differences in cardiovascular mortality is poorly understood.

Methods

We used data from the Third National Health and Nutrition Examination Survey and from the National Death Index to compare mortality for those with an electrocardiographic (ECG) diagnosis of left ventricular hypertrophy to those without left ventricular hypertrophy separately for whites, African Americans, and Latinos. We used Cox proportional hazards regression to control for other known prognostic factors.

Results

ECG left ventricular hypertrophy was significantly associated with ten-year cardiovascular mortality in all three racial/ethnic groups, both unadjusted and adjusted for other known prognostic factors. The hazard ratio for this association was significantly greater for African Americans (2.31, 95% CI 1.55–3.42) than for whites and Latinos (1.32, 95% CI 1.14–1.76 and 2.11, 95% CI 1.35–3.30 respectively) independent of systolic blood pressure.

Conclusions

ECG left ventricular hypertrophy contributes more to the risk of cardiovascular mortality in African Americans than it does in Whites. Using regression of ECG left ventricular hypertrophy as a goal of therapy might be a means to reduce racial differences in cardiovascular mortality; prospective validation is required.

Keywords: left ventricular hypertrophy, electrocardiography, cardiovascular risk assessment, racial/ethnic differences

Rates of cardiovascular mortality in the United States are higher for minority patients1. Hypertension might play a major role in the genesis of this mortality difference. The incidence of hypertension is greater in African Americans than in whites and Latinos. Although the incidence of hypertension is comparable in whites and Latinos, rates of controlled hypertension are significantly lower in Latinos1.

Left ventricular hypertrophy is a consequence of poor hypertension control as well as a risk factor for cardiovascular mortality independent of elevation in blood pressure2,3 perhaps because it identifies a sub-population that is particularly sensitive to the adverse effects of hypertension. Differences in prevalence of left ventricular hypertrophy by race and ethnicity might be expected to explain differences in cardiovascular mortality, but data supporting this view are scarce. In one study confined to patients with coronary heart disease, left ventricular hypertrophy by echocardiography was associated with a higher population attributable risk for mortality in African American patients than in whites4.

The aim of the current study was therefore to assess the degree to which the presence of left ventricular hypertrophy predicts mortality across race and ethnicity in community-based adults unselected with regard to co-morbidity. The study used electrocardiographic (ECG) criteria for determining left ventricular hypertrophy that are based on thresholds in the relationship between ECG parameters and mortality5. We chose to use ECG criteria because the electrocardiogram is less expensive and more widely available compared with echocardiography or magnetic resonance imaging, and thus may be more suited for application to population-wide hypertension management.

Methods

Data Sources

The data sources for the study were the Third National Health and Nutrition Examination Survey (NHANES III)6 database and the NHANES III Linked Mortality File7. NHANES III was an epidemiologic survey designed to obtain a sample representative of the civilian, non-institutionalized population of the United States greater than 2 months old between 1988 and 1994. Twelve-lead electrocardiograms were obtained from all subjects older than 40 years. Tracings were recorded at the mobile examination center and later transferred to a central location for electronic analysis.

The NHANES III Linked Mortality File contains the results of matching NHANES III subject identifiers with data available in the National Death Index8 as of December 31, 2000. Date of death and cause of death available in the National Death Index are derived from death certificates.

Inclusion criteria

We included all subjects for whom data was available to calculate the ECG measure, for whom vital status at ten years was known, and who were identified as Caucasian, African American or Hispanic. In addition, we included only those subjects with a QRS duration < 0.12 msec, since validity of the ECG measure in the presence of bundle branch block has not been established.

Definitions

We defined left ventricular hypertrophy with an ECG measure, the Novacode estimate of left ventricular mass index. We chose this measure because it had the strongest associations with mortality and the greatest percent population attributable risk compared with other validated measures in a previous study5. The reasons for the superior performance of this measure over other ECG measures for predicting mortality likely include that it accounts for the presence of obesity and for the presence of the “strain pattern” that has been demonstrated to predict mortality independently911. The Novacode system has also been found to predict cardiovascular endpoints in other prior studies12,13. This measure is calculated from a set of linear regression equations, one for African American women, one for white (including Latino) women, and one for men14:

  • Novacode LVMI African American women = 0.0216(R aVL) + 0.0184(R V6 + S V2) − 0.0143(R V2) − 0.0693(Q or S V6) + 0.199(T aVL) + 0.746(QRS duration) − 22.3064
  • Novacode LVMI white women = 0.0178(R V5) + 0.0528(Q or S V5) − 0.1128(Q or S I) + 0.1075(T V1) + 0.1701(T aVF) − 0.0939(T V6) + 88.4357
  • Novacode LVMI men = 0.01(R V5) + 0.0203(Q or S V1) + 0.0287(Q or S III) + 0.1819(T V6) − 0.1482(T aVR) + 1.0485(QRS duration) − 36.429

We considered left ventricular hypertrophy to be present when Novacode LVMI is greater than 115 gms/m2 for women and greater than 130 gms/m2 for men5.

We selected ten-year cardiovascular mortality as the primary outcome of interest. We defined cardiovascular deaths as those for which the death certificate principal cause of death was ICD-9 codes 390.0–459.9 (for deaths before or during 1999) or ICD-10 codes I10–15, I20–25, I50–51, I60–69, I70–73 (for deaths after 1999). In secondary analyses, we assessed the association between left ventricular hypertrophy and five-year cardiovascular mortality, and five- and ten-year total mortality. We also explored five- and ten-year coronary heart disease (CHD) mortality as possible outcomes of interest. Because of small numbers of CHD deaths (at ten years, whites 71 deaths, African Americans 17 deaths, Latinos 8 deaths), possibly as a result of under-coding of CHD on death certificates, multivariable analyses with CHD as an outcome are not feasible with this data set.

Statistical Analysis

Descriptive statistics and frequency distributions were generated for sociodemographic and clinical variables by race/ethnicity. Comparisons of patient characteristics across racial/ethnic groups for these variables were made with one-way analysis of variance for continuous variables and chi-square tests for binary variables.

We used Cox proportional hazards models to test whether left ventricular hypertrophy was associated with cardiovascular mortality separately among African American, Latino, and white subjects. In the first set of models (unadjusted), the presence or absence of left ventricular hypertrophy was the only independent variable. It should be noted that there is an accounting for gender inherent in this “unadjusted” model, since the presence of left ventricular hypertrophy is defined separately for men and women. In the second set, age and systolic blood pressure were added to left ventricular hypertrophy. In the third set, smoking, total and HDL cholesterol, and diabetes were added to left ventricular hypertrophy, age, and blood pressure.

We used Cox proportional hazards models with a race/ethnicity × left ventricular hypertrophy interaction term to test whether left ventricular hypertrophy was differentially associated with outcome across the three racial/ethnic categories. In the first model we included race/ethnicity, presence of left ventricular hypertrophy, and the interaction term. In the second model we included the above terms along with age and systolic blood pressure as continuous variables. In the third model we added smoking, total and HDL cholesterol, and diabetes to race/ethnicity, left ventricular hypertrophy, the interaction term, age, and blood pressure. Hazards ratios associated with left ventricular hypertrophy were estimated for the three race/ethnicity groups for all models.

Statistical analysis was performed using SAS, Version 9.1 for personal computer.

Results

There were 7495 subjects in the NHANES III data set with ECG, vital status, and race/ethnicity data that met the requirements for inclusion in the study. The mean age of the included patients was 59.5 years. Among included patients, 52.3% were women. The sample was 24.4% African American, 51.7% white, and 23.9% Latino. Clinical characteristics of the study sample are shown in Table 1. As a result of the large sample size, racial/ethnic differences were statistically significant for all variables and of small magnitude for most. The notable exception is that the prevalence of ECG left ventricular hypertrophy in African Americans was approximately twice that in Latinos and whites despite rather small differences in mean systolic blood pressure across the three groups; the prevalence of left ventricular hypertrophy by hypertension categorization did not differ across racial/ethnic categories.

Table 1
Demographic and clinical characteristics of the study sample

In unadjusted analyses, left ventricular hypertrophy was significantly associated with ten-year cardiovascular mortality for all three racial/ethnic groups (Table 2), and remained significant after adjusting first for age and systolic blood pressure and then for smoking, total and HDL cholesterol, and diabetes in addition to age and systolic blood pressure. The results of the secondary analyses with five-year cardiovascular mortality and five- and ten-year total mortality as the outcomes (Table 3) parallel the results of the primary analysis.

Table 2
Hazard ratios for 10 year cardiovascular mortality associated with left ventricular hypertrophy
Table 3
Hazard ratios for associations between secondary outcome measures and left ventricular hypertrophy, controlling for age, blood pressure, smoking, total and HDL cholesterol, and diabetes

We also assessed whether or not the effect of left ventricular hypertrophy on mortality differed across the three racial/ethnic groups (African American vs. white and Latino vs. white). As shown in Table 2, the magnitude of the association between electrocardiographically-estimated left ventricular mass index and cardiovascular mortality was not significantly different for Latino and white subjects. For African American subjects, however, the hazard ratio associated with left ventricular hypertrophy was significantly greater than the hazard ratio for white subjects in the model adjusting for age and blood pressure and was borderline greater in the fully adjusted model.

Discussion

Using data from a nationally representative epidemiological survey, we found that the presence of left ventricular hypertrophy determined by ECG was a strong predictor of subsequent cardiovascular mortality for whites, African Americans, and Latinos. The ECG indicator of left ventricular hypertrophy remained a significant predictor of outcome across all three groups after adjustment for systolic blood pressure. Furthermore, left ventricular hypertrophy was a stronger predictor of cardiovascular mortality in African Americans than it was in whites. The hazard ratios in Latinos were consistently greater than the hazard ratios in whites and consistently similar to the hazard ratios in African Americans, suggesting that the relatively low number of events in Latinos might have rendered this analysis underpowered to detect meaningful differences for this ethnic group. With five- and ten-year total mortality as outcomes the differences by race and ethnicity are muted, perhaps reflecting excess non-cardiovascular mortality in minority communities during the 1990s when the NHANES III cohort was created15.

Comparison with prior literature

Prior studies have suggested that the ECG is a less useful tool for assessing for the presence of left ventricular hypertrophy in African Americans. Lee et al16 compared the sensitivity and specificity of ECG indicators of left ventricular hypertrophy in African Americans and whites compared with echocardiography. Among 122 African American and 148 white subjects with hypertension, each of the five ECG indicators of left ventricular hypertrophy had lower specificity in African Americans compared with whites. The authors concluded that “standard ECG criteria will yield a higher number of false positive diagnoses of left ventricular hypertrophy in black hypertensives than in white hypertensives”. Chapman and colleagues17 likewise reported lower specificity for ECG indicators of left ventricular hypertrophy in African Americans compared with whites among 408 patients with hypertension. Arnett et al18 found sensitivity and specificity of ECG criteria for left ventricular hypertrophy in a community-based group of 196 African Americans to be similar to that previously reported for whites; direct racial comparisons were not reported. Okin and colleagues19, reporting data from a randomized trial of anti-hypertensive therapy, reported lower specificity for African American subjects compared with white subjects using the Sokolow-Lyons ECG indicator of left ventricular hypertrophy (R wave amplitude in lead V1 + S wave amplitude in lead V5 or V6 > 35 mm) but not the Cornell voltage indicator (R wave amplitude in lead aVL + S wave amplitude V3 > 20 mm in women or 28 mm in men). In a study of patients with coronary heart disease, left ventricular hypertrophy by echocardiography was associated with a higher population attributable risk for mortality in African American patients (20%) compared with whites (16%)4.

In contrast to the relatively large number of studies of the diagnosis and prognostic implications of left ventricular hypertrophy for African Americans, data for Latinos are scarce. It has been reported that ECG voltages in Latinos varies systematically from other ethnic groups20. A study of a database containing information on over 45,000 electrocardiograms at a single Veterans Administration hospital found a lower prevalence of left ventricular hypertrophy using the Romhilt-Estes criteria in Latinos (3.3%) compared with non- Latinos (5.3%)21. The proportion of the non-Latino group that was African American is not given. Although the presence of left ventricular hypertrophy by echocardiography has been demonstrated to be an independent predictor of vascular events in Latinos22, comparisons of the strength of the association with other demographic groups has not been reported.

The prevalence of left ventricular hypertrophy by ECG in our study is somewhat lower than the prevalence reported by Drazner and colleagues using magnetic resonance imaging and careful control for body size and composition in the Dallas Heart Study23. These investigators studied 2193 African American or white Dallas residents selected at random, with over-sampling of African American subjects in order to ensure that adequate racial comparisons could be made. They report a prevalence of left ventricular hypertrophy of 2.8% in white women and 7.7% in African American women, and 4.5% and 8.2% in white and African American men respectively. Despite differences in absolute values, the white:African American ratio of prevalences in the Dallas Heart Study is similar to that seen in our study.

Our study differs from most previous studies in three important ways. First, our indicator of left ventricular hypertrophy was defined against mortality rather than echocardiographically-determined left ventricular mass. Second, we used a relatively underutilized ECG indicator of left ventricular hypertrophy, the Novacode estimate of left ventricular mass index, which has a stronger relationship with mortality than other indicators. This indicator incorporates the T wave inversion found in the strain pattern that is associated with higher mortality911, partially accounts for obesity, and uses gender- and race-specific regression equations. Third, we assessed the impact of left ventricular hypertrophy on mortality in a community sample rather than in a sample containing only patients with hypertension or coronary heart disease.

Potential mechanisms

There are several potential reasons why Novacode left ventricular mass index above threshold might be associated with cardiovascular mortality to a greater degree in African American patients. The pattern of concentric left ventricular hypertrophy, characterized by both increased wall thickness and increased cavity dimension, has been associated with poorer prognosis in most studies2426, and African American27 and Latino28 patients are more likely to develop concentric hypertrophy compared with whites. It is possible that an increase in the Novacode left ventricular mass index reflects not only increases in mass but also changes in geometry. Genetic factors may play a role. Polymorphisms that cause a more vigorous hypertrophic response to hypertension may be more common in African Americans. There may linkage in African Americans between a predisposition to left ventricular hypertrophy and predisposition to atherosclerotic disease or cardiomyopathy. Environmental factors common among socio-economically disadvantaged patients such as chronic psychological stress or a diet more likely to result in obesity may also play a role, particularly if these environmental factors interact with genetic factors. Finally, treatment factors may play a role, with disadvantaged patients receiving less vigorous treatment subsequent to the initial examination as a result of poorer access to care.

Limitations

There are important limitations to our study. First, the study relies on cross-sectional data. Treatment patterns and blood pressure subsequent to the initial NHANES III examination are not known. Second, our definition of cardiovascular mortality relies on death certificate diagnoses rather than medical record review. Finally, our methodology relies on an ECG measure that requires computer-assisted interpretation, potentially limiting generalizability.

Conclusions

An ECG indicator of left ventricular hypertrophy, the Novacode estimate of left ventricular mass index, predicted cardiovascular mortality independent of systolic blood pressure in whites, African Americans, and Latinos. The hazard ratio for the association between left ventricular hypertrophy and outcome was greater for African Americans compared with whites. If validated in other populations, these findings suggest that electrocardiographic left ventricular hypertrophy identifies a particularly high-risk group among minority patients, who may benefit from more aggressive intervention. Electrocardiography might be a useful means of following response to treatment in minority patients with hypertension and as such might augment efforts to reduce health disparities attributable to hypertension.

Acknowledgments

This studied was supported by National Heart Lung and Blood Institute grant U01 HL079160 and by Health Resources Service Award Administrative Unit Grant HP00054 5 D12.

Footnotes

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References

1. Rosamond W, Flegal K, Friday G, et al. Heart Disease and Stroke Statistics--2007 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115:e69–e171. [PubMed]
2. Levy D, Garrison R, Savage D, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322:1561–1566. [PubMed]
3. Brown D, Giles W, Croft J. Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension. Am Heart J. 2000;140:848–856. [PubMed]
4. East M, Jollis JG, Nelson C, et al. The influence of left ventricular hypertrophy on survival inpatients with coronary artery disease: Do race and gender matter? J Am Coll Cardiol. 2003;41:949–954. [PubMed]
5. Havranek EP, Emsermann C, Bailey D, et al. Thresholds in the relationship between mortality and left ventricular hypertrophy defined by electrocardiography. J Electrocardiol. 2008 in press (e-published March 13, 2008). [PMC free article] [PubMed]
9. Verdecchia P, Schillaci G, Borgioni C, et al. Prognostic value of a new electrocardiographic method for diagnosis of left ventricular hypertrophy in essential hypertension. J Am Coll Cardiol. 1998;31:383–390. [PubMed]
10. Levy D, Salomon M, D'Agostino RB, et al. Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation. 1994;90:1786–1793. [PubMed]
11. Okin PM, Devereux R, Nieminen MS, et al. Electrocardiographic strain pattern and the prediction of cardiovascular morbidity and mortality in hypertensive patients: The LIFE Study. J Am Coll Cardiol. 2003;41:247A–248A.
12. Denes P, Larson J, Lloyd-Jones D, et al. Major and minor ECG abnormalities in asymptomatic women and risk of cardiovascular events and mortality. JAMA. 2007;297:978–985. [PubMed]
13. Rautaharju P, Manolio T, Siscovick D, et al. The Cardiovascular Health Study Collaborative Research Group. Utility of new electrocardiographic models for left ventricular mass in older adults. Hypertension. 1996;28:8–15. [PubMed]
14. Rautaharju P, Lacroix A, Savage D, et al. ECG estimate of left ventricular mass versus radiographic cardiac size and the risk of cardiovascular disease mortality in the epidemiologic Follow-Up Study of the First National Health and Nutrition Examination Survey. Am J Cardiol. 1988;62:59–66. [PubMed]
15. Harper S, Lynch J, Burris S, Davey Smith G. Trends in the black-white life expectancy gGap in the United States, 1983–2003. JAMA. 2007;297:1224–1232. [PubMed]
16. Lee D, Marantz P, Devereux R, et al. Left ventricular hypertrophy in black and white hypertensives: Standard electrocardiographic criteria overstate racial differences in prevalence. JAMA. 1992;267:3294–3299. [PubMed]
17. Chapman J, Mayet J, Chang C, et al. Ethnic differences in the identification of left ventricular hypertrophy in the hypertensive patient. Am J Hypertens. 1999;12:437–442. [PubMed]
18. Arnett D, Rautaharju P, Sutherland S, et al. Validity of electrocardiographic estimates of left ventricular hypertrophy and mass in African Americans (The Charleston Heart Study) Am J Cardiol. 1997;79:1289–1291. [PubMed]
19. Okin PM, Wright JT, Nieminen MS, et al. Ethnic differences in electrocardiographic criteria for left ventricular hypertrophy: The LIFE Study. Am J Hypertens. 2002;15:663–671. [PubMed]
20. Rautaharju P, Zhou S, Calhoun H. Ethnic differences in ECG amplitudes in North American white, black, and Hispanic men and women. J Electrocardiol. 1994;27:20–31. [PubMed]
21. Perez M, Yaw T, Myers J, Froelicher VF. Prognostic value of the computerized ECG in Hispanics. Clinical Cardiol. 2007;30:189–194. [PubMed]
22. Rodriguez C, Lin F, Sacco R, et al. Prognostic implications of left ventricular mass among Hispanics: The Northern Manhattan Study. Hypertension. 2006;48:87–92. [PubMed]
23. Drazner M, Dries DL, Peshock R, et al. Left ventricular hypertrophy is more prevalent in blacks than whites in the general population: The Dallas Heart Study. Hypertension. 2005;46:124–129. [PubMed]
24. Krumholz HM, Larson M, Levy D. Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol. 1995;25:879–884. [PubMed]
25. Ghali J, Liao Y, Cooper R. Influence of left ventricular geometric patterns on prognosis in patients with or without coronary artery disease. J Am Coll Cardiol. 1998;31:1635–1640. [PubMed]
26. Koren M, Devereux R, Casale PN, et al. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Int Med. 1991;114:345–352. [PubMed]
27. Kizer J, Arnett D, Bella J, et al. Differences in left ventricular structure between black and white hypertensive adults: The Hypertension Genetic Epidemiology Network Study. Hypertension. 2004;43:1182–1188. [PubMed]
28. Zabalgoitia M, Ur Rahman S, Haley W, et al. Impact of ethnicity on left ventricular mass and relative wall thickness in essential hypertension. Am J Cardiol. 1998;81:412–417. [PubMed]
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