Background Epidemiologic studies have shown that left ventricularhypertrophy is often found in the absence of an elevated cardiacworkload. To investigate whether such hypertrophy is determinedin part by genetic factors, we studied the association betweenthis condition, as assessed by electrocardiographic criteria,and a deletion (D)-insertion (I) polymorphism of the angiotensin-converting-enzyme(ACE) gene.
Methods A population-based random sample of 711 women and 717men 45 to 59 years of age was studied cross-sectionally in Augsburg,Germany. Electrocardiographic indexes, including the Sokolow-Lyonindex, Minnesota Code 3.1, and the Rautaharju equations, wereused to detect left ventricular hypertrophy. The status of theACE gene with respect to the deletion-insertion allele was determinedby the polymerase chain reaction in all subjects with left ventricularhypertrophy and an identical number of control subjects withoutthe condition who were matched for age, sex, and blood-pressurestatus.
Results We identified 141 women and 149 men with evidence ofleft ventricular hypertrophy. Among these subjects, an excesswere homozygous for the D allele of the ACE gene (odds ratio,1.76; 95 percent confidence interval, 1.22 to 2.53; P = 0.003).The association of the DD genotype with left ventricular hypertrophywas stronger in men (odds ratio, 2.63; 95 percent confidenceinterval, 1.50 to 4.64; P<0.001) than in women and was mostprominent when blood-pressure measurements were normal (oddsratio, 4.05; 95 percent confidence interval, 1.76 to 9.28; P= 0.001). This association was evident for each of the scoresrecorded in the electrocardiographic testing for left ventricularhypertrophy.
Conclusions The findings suggest that left ventricular hypertrophyis partially determined by genetic disposition. They identifythe DD genotype of ACE as a potential genetic marker associatedwith an elevated risk of left ventricular hypertrophy in middle-agedmen.
Left ventricular hypertrophy, a major independent risk factorfor morbidity and mortality from cardiovascular disease,1,2,3,4is widely thought to be a consequence of left ventricular pressureoverload5,6. However, the degree of such hypertrophy in patientswith mildly elevated arterial pressure is not uniform and mayrange from normal ventricular mass to severe hypertrophy6,7.Furthermore, recent epidemiologic studies have shown that manysubjects with left ventricular hypertrophy have normal bloodpressure, suggesting that factors other than hemodynamic overloadmay contribute to the hypertrophy4.
Neuroendocrine factors such as angiotensin II and bradykininhave been implicated in the modulation of cardiac growth8,9.Experimental studies suggest that angiotensin II may stimulatecardiac protein synthesis,10,11,12 whereas bradykinin may havean antiproliferative effect13. Angiotensin-converting enzyme(ACE) is a key enzyme in the production of angiotensin II aswell as the degradation of bradykinin and thus may participatein the modulation of cardiac growth. In addition, recent studiesof experimental left ventricular hypertrophy due to pressureoverload as well as studies in patients with dilated cardiomyopathyhave demonstrated elevated cardiac expression of ACE messengerRNA and ACE activity14,15,16.
The cloning of the ACE gene has made it possible to identifya deletion (D)-insertion (I) polymorphism that appears to affectthe level of serum ACE activity17,18,19. More important, thegenotype (DD) with the highest ACE levels may be a risk factorfor myocardial infarction as well as dilated and hypertrophiccardiomyopathy20,21,22. We explored a possible association betweenhomozygosity of the ACE D allele (the DD genotype) and leftventricular hypertrophy identified by electrocardiography ina population-based random sample of 1428 Western Europeans.
Methods
Study Population
The cross-sectional study was carried out in Augsburg, Germany,as part of the Multinational Monitoring of Trends and Determinantsin Cardiovascular Disease project of the World Health Organization23,24.Eligible participants were initially sampled at random in 1984-1985(in a two-stage cluster sampling stratified for age and sex)from all inhabitants of a mixed urban and rural area. All whoparticipated in the first follow-up examination in 1987-1988(participation rate, 93.1 percent) were included after theygave informed consent to participate in the study. The studypopulation comprised 711 women and 717 men, 45 to 59 years ofage. All the subjects were whites of Western European descent.
All the subjects responded to a questionnaire on their medicalhistory and lifestyle. Laboratory evaluations for the determinationof blood count and cholesterol were carried out with standardmethods. Blood pressure was measured three times with a random-zerodevice (Hawksley, Lancing, United Kingdom), and strict qualitycontrol was applied. The mean of the last two measurements wasused. Hypertension was defined as a systolic blood pressureof 160 mm Hg or higher, a diastolic blood pressure of 95 mmHg or higher, or both. The status of antihypertensive treatmentwas assessed on the basis of the prescriptions used during theweek before the interview. Standard 12-lead electrocardiogramswere recorded in all patients and analyzed with a digital system.Left ventricular hypertrophy was defined according to publishedcriteria, with the Sokolow-Lyon index,25 Minnesota Code 3.1,26and Rautaharju equations (for both men and women)27. Subjectswith evidence of bundle-branch block or Wolff-Parkinson-Whitesyndrome were excluded from the analysis.
Extraction and Amplification of Genomic DNA
DNA was prepared from frozen peripheral blood with standardprocedures28. Briefly, 500 microl of blood was diluted in 4.5ml of buffer (155 mM ammonium chloride, 10 mM potassium carbonate,and 0.1 mM EDTA; pH 8.0), vortexed, and centrifuged. The pelletswere resuspended in 100 microl of buffer (10 mM TRIS-hydrochloricacid and 1 mM EDTA; pH 8.0) to which 300 microl of lysis buffer(400 mM sodium chloride, 10 mM TRIS-hydrochloric acid, and 2mM EDTA; pH 8.0), 15 microl of sodium dodecyl sulfate (20 percent),and 30 microl of proteinase K (10 mg per milliliter of solution)were added. Overnight digestion with proteinase K at 55 °Cwas followed by centrifugation and precipitation of the supernatantin ethanol. The polymerase chain reaction (PCR) was carriedout as described elsewhere,29 except that glycerine (2.5 microl)was added to the reaction mixture. The PCR products were denaturedand separated by agarose-gel electrophoresis21.
Statistical Analysis
Subjects were considered to have left ventricular hypertrophyif they fulfilled any of the three electrocardiographic criteria.Controls were selected from the remaining subjects and matchedone-to-one for age, sex, and blood-pressure status (i.e., normotensive,normotensive with antihypertensive treatment, hypertensive withantihypertensive treatment, or hypertensive without treatment).
The statistical analyses were based on the calculation of oddsratios to provide an estimate of the relative risk of left ventricularhypertrophy in groups of subjects with different genotypes.To account for the influence of matching, odds ratios were calculatedfor all pairs, for men and women separately, and for prespecifiedsubgroups defined according to blood-pressure status30. Theanalyses were performed by means of conditional logistic-regressionmodels that, in the final stage, also included potential confoundingvariables such as body-mass index, blood pressure, and heartrate as a continuous variable.
Results
The screening of this large, population-based sample identifiedelectrocardiographic evidence of left ventricular hypertrophyin 141 women and 149 men. The demographic characteristics ofthe subjects with left ventricular hypertrophy and the matchedcontrols did not differ significantly with regard to systolicand diastolic blood pressure, heart rate, body-mass index, hematocrit,total and high-density lipoprotein cholesterol, or smoking behavior(data not shown).
The distribution of the DD, ID, and II genotypes in the controlgroup was 24.8 percent, 58.6 percent, and 16.6 percent, respectively;there was an overall frequency of 54 percent for the D alleleand 46 percent for the I allele (Table 1), which compares closelywith other white populations studied19,20. In contrast, thegroup with left ventricular hypertrophy was characterized byan excess of subjects homozygous for the D allele (Table 1).Analyses of the matched pairs revealed that the DD genotypewas associated with a significantly increased risk of left ventricularhypertrophy, as detected by electrocardiography (Table 1).
Table 1. Distribution of ACE Genotypes among Middle-Aged Subjects with Left Ventricular Hypertrophy and Matched Controls.
The DD genotype was not associated with a significant increasein the risk of left ventricular hypertrophy in women (odds ratio,1.22; 95 percent confidence interval, 0.84 to 1.77; P = 0.42).In contrast, men who were homozygous for the D allele (i.e.,who had the DD genotype) more often had electrocardiographicevidence of left ventricular hypertrophy than did those withthe ID and II genotypes (odds ratio, 2.63; 95 percent confidenceinterval, 1.50 to 4.64; P<0.001) (Table 1).
A substantial proportion of women and men with electrocardiographicevidence of left ventricular hypertrophy were found to be normotensive.Figure 1 shows the increasing prevalence of left ventricularhypertrophy in subjects with borderline blood-pressure readingsor readings indicating hypertension; in absolute numbers, however,the majority of subjects with left ventricular hypertrophy (asdefined by all the electrocardiographic criteria combined) hadnormal blood-pressure readings (Figure 1). Therefore, we studiedprespecified subgroups to determine whether the associationbetween the DD genotype of the ACE gene and left ventricularhypertrophy was influenced by blood-pressure levels. Interestingly,the strongest association was found when blood pressure wasnormal (Figure 2 and Table 2). The association of the DD genotypewith left ventricular hypertrophy was evident in groups of normotensivemiddle-aged men with the condition as identified by the Sokolow-Lyonindex, Minnesota Code 3.1, or the Rautaharju equations, as wellas in the combined group, for which the odds ratio reached 4.05(P = 0.001) (Table 2).
Figure 1. Percentage of Subjects with Electrocardiographically Detected Left Ventricular Hypertrophy (LVH), According to Blood Pressure.
The prevalence of LVH increased with increasing blood pressure. Absolute numbers of subjects with the condition, shown below the graph, indicate that the majority were normotensive. Sixteen men and 25 women receiving antihypertensive medication were excluded from this analysis.
Figure 2. Odds Ratios and 95 Percent Confidence Intervals for Left Ventricular Hypertrophy in Subjects Homozygous for the D Allele of the ACE Gene.
The strongest association between the ACE DD genotype and electrocardiographically detected left ventricular hypertrophy was found among normotensive men.
Table 2. Distribution of ACE Genotypes among Normotensive and Hypertensive Men with Left Ventricular Hypertrophy and Matched Controls.
Additional covariables were not related to the ACE genotype.Conditional logistic-regression analyses demonstrated that thesignificant association of the DD genotype with electrocardiographicevidence of left ventricular hypertrophy was independent ofpossible confounding variables, such as blood pressure, heartrate, body-mass index, lipid profile, hematocrit, and cigaretteconsumption (data not shown). Likewise, excluding subjects withelectrocardiographic evidence of myocardial infarction (12 menand 1 woman) or ischemia at rest (9 men and 3 women) did notaffect the observed association between the DD genotype andleft ventricular hypertrophy detected by electrocardiography.
Discussion
Our results strongly suggest that genetic background, in additionto hemodynamic overload,5,6 obesity,31 and certain environmentalfactors,32 may influence the development of left ventricularhypertrophy. The idea that genetic background contributes tothe regulation of cardiac hypertrophy originated in studiesof twins. The investigation by Adams et al. suggested that leftventricular mass is partly determined by familial influences33.Verhaaren et al. concluded that over 60 percent of the variabilityin left ventricular mass can be explained by heritable factors34.Our study extends these findings by identifying a moleculargenetic marker, a deletion polymorphism in intron 16 of theACE gene, that is associated with electrocardiographic evidenceof left ventricular hypertrophy.
Further analyses identified two factors that affected the associationbetween the ACE DD genotype and left ventricular hypertrophy.First, among men homozygous for the deletion allele of the ACEgene, the odds of meeting the electrocardiographic criteriafor left ventricular hypertrophy were 2.63 times greater thanamong the other men, whereas no significant association wasseen among women. Interestingly, previous epidemiologic studiespointed out that the heritability of left ventricular mass aswell as the incidence of left ventricular hypertrophy may differbetween men and women, suggesting sex-related differences inthe pathogenesis of the condition4,34.
Second, 62 percent of the subjects with electrocardiographicevidence of left ventricular hypertrophy in this study werefound not to have hypertension. This finding, although surprising,agrees with prior population-based studies. In particular, Levyet al. reported for the Framingham Heart Study that 56 percentof middle-aged women and 57 percent of middle-aged men withleft ventricular hypertrophy identified by echocardiographyhad systolic blood-pressure readings below 140 mm Hg4. In thepresent study, the large number of normotensive subjects withleft ventricular hypertrophy allowed us to test whether theassociation of that condition with the ACE deletion-insertionpolymorphism was influenced by blood pressure. Interestingly,the strongest association between the ACE DD genotype and leftventricular hypertrophy was identified when blood pressure wasnormal. We postulate that the effect of the DD genotype on thedevelopment of left ventricular hypertrophy may be strongerwhen no other causative factors are present, such as left ventricularpressure overload.
A potential limitation of this study is that the identificationof left ventricular hypertrophy by electrocardiography may haveinfluenced the results. Electrocardiography is less sensitivethan echocardiography for the estimation of left ventricularmass2; however, digital and automated electrocardiographic interpretationcarries the advantage of unbiased classification of left ventricularhypertrophy and allows screening in large populations such asours3. The clinical relevance of the electrocardiographic indexesused may be underscored by an increased mortality from cardiovascularcauses among subjects with electrocardiographic evidence ofleft ventricular hypertrophy1,3,27. Finally, to reduce furtherany potential bias created by the use of electrocardiographiccriteria, we carried out three analyses with different electrocardiographicscores for left ventricular hypertrophy. All the electrocardiographicindexes used identified an increased risk of left ventricularhypertrophy among normotensive men homozygous for the D alleleof ACE.
Our study does not identify the mechanism by which the DD genotypeof the ACE gene may affect cardiac hypertrophy. Since some componentsof the renin-angiotensin system have been genetically linkedto arterial hypertension,35,36,37 elevation of blood pressurein itself could potentially account for the increased incidenceof left ventricular hypertrophy in subjects homozygous for theACE D allele. This explanation seems unlikely. First, the ACEpolymorphism did not show linkage with blood pressure in twoprevious studies19,38 or in this one (data not shown). Second,in the present study, the subjects with left ventricular hypertrophyand the control subjects were matched by the study design forthe presence (or absence) of hypertension and antihypertensivetreatment. Finally, the association of the ACE DD genotype wasmost prominent when blood pressure was normal. Thus, even ifa potential interaction of exercise-related or situational hypertensioncannot be fully excluded, the association of the ACE DD genotypeand left ventricular hypertrophy seems to involve other mechanismsthan blood-pressure levels. In this regard, it may be of interestthat a meta-analysis of multiple clinical studies has suggestedthat pharmacologic inhibitors of ACE may be superior to someother antihypertensive agents in inducing regression of cardiachypertrophy, even though they have similar effects on bloodpressure39. Furthermore, ACE inhibitors promote better survivalin heart failure than do other vasodilators40. Therefore, clinicaldata support the hypothesis that the inhibition of ACE may affectcardiac structure and function by mechanisms other than simplereduction in blood pressure.
The data do not permit us to conclude definitely that the Dallele of ACE mediates the development of left ventricular hypertrophy.Alternatively, the DD genotype may serve as a marker of a criticalgene in close proximity. Thus, it is certainly premature tospeculate whether the association of the ACE DD genotype andleft ventricular hypertrophy may affect outcomes for patientstreated with ACE inhibitors. A final limitation is that thisstudy examined a Western European population composed of whiteadults. Further population-based studies are needed to determinewhether homozygosity for the ACE D allele is associated withan increased risk of hypertrophy in normotensive adults fromother geographic areas and racial backgrounds. However, thisstudy suggests that genetic disposition may substantially contributeto the development of left ventricular hypertrophy in normotensivesubjects.
Supported by a grant (DFG Schu 617/3-1) from the Deutsche Forschungsgemeinschaft,by an Astra Award for Cardiovascular Research, and by the Bundesministeriumfur Forschung und Technologie. Dr. Lorell is an EstablishedInvestigator of the American Heart Association.
We are indebted to Ingrid Kirst, Peter Schickling, and GuntherBruckschlegel for technical assistance, and to Dr. CharalamposAslanidis for critical discussion of this work.
Source Information
From the Medizinische Klinik II, University of Regensburg, Regensburg, Germany (H.S., S.R.H., G.A.J.R.); the Institut fur Epidemiologie (H.-W.H., M.S., U.K.) and the MEDIS Institut (S.P.), GSF Forschungszentrum, Munchen-Neuherberg, Germany; the Institut fur Epidemiologie und Sozialmedizin (H.-W.H., U.K.), University of Munster, Munster, Germany; and the Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Internal Medicine, Cardiovascular Division, Beth Israel Hospital and Harvard Medical School, Boston (B.H.L.). Presented in part at the 66th scientific sessions of the American Heart Association, Atlanta, November 8-11, 1993.
Address reprint requests to Dr. Schunkert at the Klinik and Poliklinik fur Innere Medizin II, Universitat Regensburg, Franz-Josef Strauss Allee, D-93053 Regensburg, Germany.
References
Kannel WB, Gordon T, Castelli WP, Margolis JR. Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease: the Framingham Study. Ann Intern Med 1970;72:813-822.
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;322:1561-1566. [Abstract]
Sullivan JM, Vander Zwaag RV, el-Zeky F, Ramanathan KB, Mirvis DM. Left ventricular hypertrophy: effect on survival. J Am Coll Cardiol 1993;33:508-513.
Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors: the Framingham Heart Study. Ann Intern Med 1988;108:7-13.
Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975;56:56-64.
Ganau A, Devereux RB, Pickering TG, et al. Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension. Circulation 1990;81:25-36. [Free Full Text]
Drayer JIM, Weber MA, DeYoung JL. BP as a determinant of cardiac left ventricular muscle mass. Arch Intern Med 1983;143:90-92. [Free Full Text]
Morgan HE, Baker KM. Cardiac hypertrophy: mechanical, neural, and endocrine dependence. Circulation 1991;83:13-25. [Free Full Text]
Lindpaintner K, Ganten D. The cardiac renin-angiotensin system: an appraisal of present experimental and clinical evidence. Circ Res 1991;68:905-921. [Free Full Text]
Khairallah PA, Kanabus J. Angiotensin and myocardial protein synthesis. Perspect Cardiovasc Res 1983;8:337-47.
Sadoshima J-I, Izumo S. Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts: critical role of the AT1 receptor subtype. Circ Res 1993;73:413-423. [Free Full Text]
Farhy RD, Ho KL, Carretero OA, Scicli AG. Kinins mediate the antiproliferative effect of ramipril in rat carotid artery. Biochem Biophys Res Commun 1992;182:283-288. [CrossRef][Medline]
Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy: effects on coronary resistance, contractility, and relaxation. J Clin Invest 1990;86:1913-1920.
Schunkert H, Jackson B, Tang SS, et al. Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation 1993;87:1328-1339. [Free Full Text]
Studer R, Muller B, Reinecke H, Just H, Holtz J, Drexler H. Quantified RNA-polymerase chain reaction demonstrates augmented gene expression of angiotensin converting enzyme in ventricles of patients with heart failure. Circulation 1992;86:Suppl I:I-119.abstract
Soubrier F, Alhenc-Gelas F, Hubert C, et al. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci U S A 1988;85:9386-9390. [Free Full Text]
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343-1346.
Harrap SB, Davidson HR, Connor JM, et al. The angiotensin I converting enzyme gene and predisposition to high blood pressure. Hypertension 1993;21:455-460. [Free Full Text]
Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641-644. [CrossRef][Medline]
Raynolds MV, Bristow MR, Bush EW, et al. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet 1993;342:1073-1075. [CrossRef][Medline]
Marian AJ, Yu Q-T, Workman R, Greve G, Roberts R. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet 1993;342:1085-1086. [CrossRef][Medline]
Keil U, Stieber J, Doring A, et al. The cardiovascular risk factor profile in the study area Augsburg: results from the first MONICA survey 1984/85. Acta Med Scand Suppl 1988;728:119-128. [Medline]
Bothig S. WHO MONICA Project: objectives and design. Int J Epidemiol 1989;18:Suppl 1:S29-S37. [Abstract]
Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J 1949;37:161-186. [CrossRef][Medline]
Prineas RJ, Crow RS, Blackburn H. The Minnesota code manual of electrocardiographic findings: standards and procedures for measurement and classification. Littleton, Mass.: John Wright/PSG, 1982.
Rautaharju PM, LaCroix AZ, Savage DD, et al. Electrocardiographic 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. [Medline]
Leadon SA, Cerutti PA. A rapid and mild procedure for the isolation of DNA from mammalian cells. Anal Biochem 1982;120:282-288. [CrossRef][Medline]
Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992;20:1433-1433. [Free Full Text]
Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research: principles and quantitative methods. Belmont, Calif.: Lifetime Learning, 1982.
Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry: the Framingham Heart Study. JAMA 1991;266:231-236. [Free Full Text]
Lindpaintner K, Sen S. Role of sodium in hypertensive cardiac hypertrophy. Circ Res 1985;57:610-617. [Free Full Text]
Adams TD, Yanowitz FG, Fisher AG, et al. Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins. Circulation 1985;71:39-44. [Free Full Text]
Verhaaren HA, Schieken RM, Mosteller M, Hewitt JK, Eaves LJ, Nance WE. Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study). Am J Cardiol 1991;68:661-668. [CrossRef][Medline]
Rapp JP, Wang SM, Dene H. A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure. Science 1989;243:542-544. [Free Full Text]
Jacob HJ, Lindpaintner K, Lincoln SE, et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 1991;67:213-224. [CrossRef][Medline]
Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992;71:169-180. [CrossRef][Medline]
Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM. Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1992;1:72-75. [CrossRef][Medline]
Dahlof B, Pennert K, Hansson L. Regression of left ventricular hypertrophy -- a meta-analysis. Clin Exp Hypertens [A] 1992;14:173-80.
Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303-310. [Abstract]
Vasan, R. S., Glazer, N. L., Felix, J. F., Lieb, W., Wild, P. S., Felix, S. B, Watzinger, N., Larson, M. G., Smith, N. L., Dehghan, A., Grosshennig, A., Schillert, A., Teumer, A., Schmidt, R., Kathiresan, S., Lumley, T., Aulchenko, Y. S., Konig, I. R., Zeller, T., Homuth, G., Struchalin, M., Aragam, J., Bis, J. C., Rivadeneira, F., Erdmann, J., Schnabel, R. B., Dorr, M., Zweiker, R., Lind, L., Rodeheffer, R. J., Greiser, K. H., Levy, D., Haritunians, T., Deckers, J. W., Stritzke, J., Lackner, K. J., Volker, U., Ingelsson, E., Kullo, I., Haerting, J., O'Donnell, C. J., Heckbert, S. R., Stricker, B. H., Ziegler, A., Reffelmann, T., Redfield, M. M., Werdan, K., Mitchell, G. F., Rice, K., Arnett, D. K., Hofman, A., Gottdiener, J. S., Uitterlinden, A. G., Meitinger, T., Blettner, M., Friedrich, N., Wang, T. J., Psaty, B. M., van Duijn, C. M., Wichmann, H.-E., Munzel, T. F., Kroemer, H. K., Benjamin, E. J., Rotter, J. I., Witteman, J. C., Schunkert, H., Schmidt, H., Volzke, H., Blankenberg, S.
(2009). Genetic Variants Associated With Cardiac Structure and Function: A Meta-analysis and Replication of Genome-wide Association Data. JAMA
302: 168-178
[Abstract][Full Text]
Mayosi, B. M., Avery, P. J., Farrall, M., Keavney, B., Watkins, H.
(2008). Genome-wide linkage analysis of electrocardiographic and echocardiographic left ventricular hypertrophy in families with hypertension. Eur Heart J
29: 525-530
[Abstract][Full Text]
Lin, T.-H., Chiu, H.-C., Lee, Y.-T., Su, H.-M., Voon, W.-C., Liu, H.-W., Lai, W.-T., Sheu, S.-H.
(2007). Association Between Functional Polymorphisms of Renin-Angiotensin System, Left Ventricular Mass, and Geometry Over 4 Years in a Healthy Chinese Population Aged 60 Years and Older. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
62: 1157-1163
[Abstract][Full Text]
Amir, O., Amir, R., Yamin, C., Attias, E., Eynon, N., Sagiv, M., Sagiv, M., Meckel, Y.
(2007). Human, Environmental & Exercise: The ACE deletion allele is associated with Israeli elite endurance athletes. Exp Physiol
92: 881-886
[Abstract][Full Text]
Shen, Y., Xu, Q., Han, Z., Liu, H., Zhou, G.-B.
(2007). Analysis of phenotype-genotype connection: the story of dissecting disease pathogenesis in genomic era in China, and beyond. Phil Trans R Soc B
362: 1043-1061
[Abstract][Full Text]
Arndt, P. G., Young, S. K., Poch, K. R., Nick, J. A., Falk, S., Schrier, R. W., Worthen, G. S.
(2006). Systemic Inhibition of the Angiotensin-Converting Enzyme Limits Lipopolysaccharide-Induced Lung Neutrophil Recruitment through Both Bradykinin and Angiotensin II-Regulated Pathways. J. Immunol.
177: 7233-7241
[Abstract][Full Text]
Sayed-Tabatabaei, F.A., Oostra, B.A., Isaacs, A., van Duijn, C.M., Witteman, J.C.M.
(2006). ACE Polymorphisms. Circ. Res.
98: 1123-1133
[Abstract][Full Text]
Hueb, J. C., Zanati, S. G., Okoshi, K., Raffin, C. N., de Arruda Silveira, L. V., Matsubara, B. B.
(2006). Association Between Atherosclerotic Aortic Plaques and Left Ventricular Hypertrophy in Patients With Cerebrovascular Events. Stroke
37: 958-962
[Abstract][Full Text]
Koch, W., Latz, W., Eichinger, M., Ganser, C., Schomig, A., Kastrati, A.
(2005). Genotyping of the Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism by the TaqMan Method. Clin. Chem.
51: 1547-1549
[Full Text]
Lin, L., Finn, L., Zhang, J., Young, T., Mignot, E.
(2004). Angiotensin-converting Enzyme, Sleep-disordered Breathing, and Hypertension. Am. J. Respir. Crit. Care Med.
170: 1349-1353
[Abstract][Full Text]
Karagiannis, A., Balaska, K., Tziomalos, K., Gerasimidis, T., Karamanos, D., Papayeoryiou, A., Zamboulis, C.
(2004). Lack of an association between angiotensin converting enzyme gene polymorphism and peripheral arterial occlusive disease. Vasc Med
9: 189-192
[Abstract]
Tian, X.-L., Pinto, Y. M., Costerousse, O., Franz, W. M., Lippoldt, A., Hoffmann, S., Unger, T., Paul, M.
(2004). Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats. Hum Mol Genet
13: 1441-1450
[Abstract][Full Text]
Hernandez, D.
(2004). Left ventricular hypertrophy after renal transplantation: new approach to a deadly disorder. Nephrol Dial Transplant
19: 1682-1686
[Full Text]
Yasunari, K., Maeda, K., Watanabe, T., Nakamura, M., Yoshikawa, J., Asada, A.
(2004). Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy. J Am Coll Cardiol
43: 2116-2123
[Abstract][Full Text]
Wiwanitkit, V.
(2004). Angiotensin-converting Enzyme Gene Polymorphism: I and D Alleles From Some Different Countries. CLIN APPL THROMB HEMOST
10: 179-182
[Abstract]
Petrovic, D., Bregar, D., Guzic-Salobir, B., Skof, E., Span, M., Terzic, R., Petrovic, M. G., Keber, I., Letonja, M., Zorc, M., Podbregar, M., Peterlin, B.
(2004). Sex Difference in the Effect of ACE-DD Genotype on the Risk of Premature Myocardial Infarction. ANGIOLOGY
55: 155-158
[Abstract]
Ocaranza, M. P., Diaz-Araya, G., Carreno, J. E., Munoz, D., Riveros, J. P., Jalil, J. E., Lavandero, S.
(2004). Polymorphism in gene coding for ACE determines different development of myocardial fibrosis in rats. Am. J. Physiol. Heart Circ. Physiol.
286: H498-H506
[Abstract][Full Text]
Huang, W., Xie, C., Zhou, H., Yang, T., Sun, M.
(2004). Association of the angiotensin-converting enzyme gene polymorphism with chronic heart failure in Chinese Han patients. Eur J Heart Fail
6: 23-27
[Abstract][Full Text]
Hernandez, D., de la Rosa, A., Barragan, A., Barrios, Y., Salido, E., Torres, A., Martin, B., Laynez, I., Duque, A., De Vera, A., Lorenzo, V., Gonzalez, A.
(2003). The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes. J Am Coll Cardiol
42: 527-532
[Abstract][Full Text]
Mulder, H J G H, van Geel, P P, Schalij, M J, van Gilst, W H, Zwinderman, A H, Bruschke, A V G
(2003). DD ACE gene polymorphism is associated with increased coronary artery endothelial dysfunction: the PREFACE trial. Heart
89: 557-558
[Full Text]
Hoeper, M M, Tacacs, A, Stellmacher, U, Lichtinghagen, R
(2003). Lack of association between angiotensin converting enzyme (ACE) genotype, serum ACE activity, and haemodynamics in patients with primary pulmonary hypertension. Heart
89: 445-446
[Full Text]
Palmer, B. R., Pilbrow, A. P., Yandle, T. G., Frampton, C. M., Richards, A. M., Nicholls, M. G., Cameron, V. A.
(2003). Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction. J Am Coll Cardiol
41: 729-736
[Abstract][Full Text]
Swan, L., Birnie, D.H., Padmanabhan, S., Inglis, G., Connell, J.M.C., Hillis, W.S.
(2003). The genetic determination of left ventricular mass in healthy adults. Eur Heart J
24: 577-582
[Abstract][Full Text]
Abraham, W. T, Raynolds, M. V, Badesch, D. B, Wynne, K. M, Groves, B. M, Roden, R. L, Robertson, A. D, Lowes, B. D, Zisman, L. S, Voelkel, N. F, Bristow, M. R, Perryman, M B.
(2003). Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics. Journal of Renin-Angiotensin-Aldosterone System
4: 27-30
[Abstract]
Choi, Y.-H., Kim, J.-H., Kim, D. K., Kim, J.-W., Kim, D.-K., Lee, M. S., Kim, C. H., Park, S. C.
(2003). Distributions of ACE and APOE Polymorphisms and Their Relations With Dementia Status in Korean Centenarians. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
58: M227-231
[Abstract][Full Text]
Pereira, A. C., Mota, G. F.A., Cunha, R. S., Herbenhoff, F. L., Mill, J. G., Krieger, J. E.
(2003). Angiotensinogen 235T Allele "Dosage" Is Associated With Blood Pressure Phenotypes. Hypertension
41: 25-30
[Abstract][Full Text]
Mayosi, B. M., Keavney, B., Kardos, A., Davies, C. H., Ratcliffe, P. J., Farrall, M., Watkins, H.
(2002). Electrocardiographic measures of left ventricular hypertrophy show greater heritability than echocardiographic left ventricular mass. Eur Heart J
23: 1963-1971
[Abstract]
Herrmann, S.-M., Nicaud, V., Schmidt-Petersen, K., Pfeifer, J., Erdmann, J., McDonagh, T., Dargie, H. J., Paul, M., Regitz-Zagrosek, V.
(2002). Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies. Eur J Heart Fail
4: 707-712
[Abstract][Full Text]
Fernandez-Sola, J., Nicolas, J. M., Oriola, J., Sacanella, E., Estruch, R., Rubin, E., Urbano-Marquez, A.
(2002). Angiotensin-Converting Enzyme Gene Polymorphism Is Associated with Vulnerability to Alcoholic Cardiomyopathy. ANN INTERN MED
137: 321-326
[Abstract][Full Text]
Raso, F. M., van Popele, N. M., Schalekamp, M. A. D. H., van der Cammen, T. J. M.
(2002). Intima-Media Thickness of the Common Carotid Arteries Is Related to Coronary Atherosclerosis and left Ventricular Hypertrophy in Older Adults. ANGIOLOGY
53: 569-574
[Abstract]
Volzke, H., Engel, J., Kleine, V., Schwahn, C., Dahm, J. B., Eckel, L., Rettig, R.
(2002). Angiotensin I-Converting Enzyme Insertion/Deletion Polymorphism and Cardiac Mortality and Morbidity After Coronary Artery Bypass Graft Surgery*. Chest
122: 31-36
[Abstract][Full Text]
Ortlepp, J R, Vosberg, H P, Reith, S, Ohme, F, Mahon, N G, Schroder, D, Klues, H G, Hanrath, P, McKenna, W J
(2002). Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart
87: 270-275
[Abstract][Full Text]
Fischer, M., Baessler, A., Schunkert, H.
(2002). Renin angiotensin system and gender differences in the cardiovascular system. Cardiovasc Res
53: 672-677
[Abstract][Full Text]
Mayer, N J, Forsyth, A, Kantachuvesiri, S, Mullins, J J, Fleming, S
(2002). Association of the D allele of the angiotensin I converting enzyme polymorphism with malignant vascular injury. Mol. Pathol.
55: 29-33
[Abstract][Full Text]
Rahmutula, D., Nakayama, T., Izumi, Y., Ozawa, Y., Shimabukuro, H., Kawamura, H., Zhen-Wang, S., Xiong-Wang, J., Aisa, M., Run-Yang, C., Mahmut, M., Mahsut, R., Hen-Chen, Z.
(2002). Angiotensin-Converting Enzyme Gene and Longevity in the Xin Jiang Uighur Autonomous Region of China: An Association Study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
57: M57-60
[Abstract][Full Text]
Fava, S., Azzopardi, J., Ellard, S., Hattersley, A. T.
(2001). ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease. Diabetes Care
24: 2115-2120
[Abstract][Full Text]
Francke, S., Manraj, M., Lacquemant, C., Lecoeur, C., Lepretre, F., Passa, P., Hebe, A., Corset, L., Yan, S. L. K., Lahmidi, S., Jankee, S., Gunness, T. K., Ramjuttun, U. S., Balgobin, V., Dina, C., Froguel, P.
(2001). A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Hum Mol Genet
10: 2751-2765
[Abstract][Full Text]
Mathew, J., Basheeruddin, K., Prabhakar, S.
(2001). Differences in Frequency of the Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene in Different Ethnic Groups. ANGIOLOGY
52: 375-379
[Abstract]
Mannami, T., Katsuya, T., Baba, S., Inamoto, N., Ishikawa, K., Higaki, J., Ogihara, T., Ogata, J.
(2001). Low Potentiality of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism as a Useful Predictive Marker for Carotid Atherogenesis in a Large General Population of a Japanese City : The Suita Study. Stroke
32: 1250-1256
[Abstract][Full Text]
Jeron, A, Hengstenberg, C, Engel, S, Lowel, H, Riegger, G.A.J, Schunkert, H, Holmer, S
(2001). The D-allele of the ACE polymorphism is related to increased QT dispersion in 609 patients after myocardial infarction. Eur Heart J
22: 663-668
[Abstract]
Barcelo, A., Elorza, M.A., Barbe, F., Santos, C., Mayoralas, L.R., Agusti, A.G.N.
(2001). Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms. Eur Respir J
17: 728-732
[Abstract][Full Text]
Rossi, G. P., Taddei, S., Virdis, A., Ghiadoni, L., Albertin, G., Favilla, S., Sudano, I., Pessina, A. C., Salvetti, A.
(2001). Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction. Hypertension
37: 293-300
[Abstract][Full Text]
Schmieder, R. E., Erdmann, J., Delles, C., Jacobi, J., Fleck, E., Hilgers, K., Regitz-Zagrosek, V.
(2001). Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans. J Am Coll Cardiol
37: 175-182
[Abstract][Full Text]
Padmanabhan, N., Padmanabhan, S., Connell, J. M.
(2000). Genetic basis of cardiovascular disease -- the renin-angiotensin-aldosterone system as a paradigm. Journal of Renin-Angiotensin-Aldosterone System
1: 316-324
Tsujita, Y., Iwai, N., Tamaki, S., Nakamura, Y., Nishimura, M., Kinoshita, M.
(2000). Genetic mapping of quantitative trait loci influencing left ventricular mass in rats. Am. J. Physiol. Heart Circ. Physiol.
279: H2062-H2067
[Abstract][Full Text]
Crisan, D., Carr, J.
(2000). Angiotensin I-Converting Enzyme: Genotype and Disease Associations. J. Mol. Diagn.
2: 105-115
[Full Text]
Hsieh, M.-C., Lin, S.-R., Hsieh, T.-J., Hsu, C.-H., Chen, H.-C., Shin, S.-J., Tsai, J.-H.
(2000). Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant
15: 1008-1013
[Abstract][Full Text]
Rankinen, T., Gagnon, J., Perusse, L., Chagnon, Y. C., Rice, T., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., Bouchard, C.
(2000). AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study. Am. J. Physiol. Heart Circ. Physiol.
279: H368-H374
[Abstract][Full Text]
Quinones, M. A., Greenberg, B. H., Kopelen, H. A., Koilpillai, C., Limacher, M. C., Shindler, D. M., Shelton, B. J., Weiner, D. H., for the SOLVD Investigators,
(2000). Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. J Am Coll Cardiol
35: 1237-1244
[Abstract][Full Text]
van Geel, P. P., Pinto, Y. M., Voors, A. A., Buikema, H., Oosterga, M., Crijns, H. J. G. M., van Gilst, W. H.
(2000). Angiotensin II Type 1 Receptor A1166C Gene Polymorphism Is Associated With an Increased Response to Angiotensin II in Human Arteries. Hypertension
35: 717-721
[Abstract][Full Text]
Bray, M. S.
(2000). Genomics, genes, and environmental interaction: the role of exercise. J. Appl. Physiol.
88: 788-792
[Abstract][Full Text]
Poch, E., Gonzalez, D., Gomez-Angelats, E., Enjuto, M., Pare, J. C., Rivera, F., de la Sierra, A.
(2000). G-Protein {beta}3 Subunit Gene Variant and Left Ventricular Hypertrophy in Essential Hypertension. Hypertension
35: 214-218
[Abstract][Full Text]
Andersson, B., Blange, I., Sylven, C.
(1999). Angiotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure. Eur J Heart Fail
1: 363-369
[Abstract][Full Text]
Alvarez, R., Alvarez, V., Lahoz, C. H, Martinez, C., Pena, J., Sanchez, J. M, Guisasola, L. M, Salas-Puig, J., Moris, G., Vidal, J. A, Ribacoba, R., Menes, B. B, Uria, D., Coto, E.
(1999). Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry
67: 733-736
[Abstract][Full Text]
Olivieri, O., Trabetti, E., Grazioli, S., Stranieri, C., Friso, S., Girelli, D., Russo, C., Pignatti, P. F., Mansueto, G., Corrocher, R.
(1999). Genetic Polymorphisms of the Renin-Angiotensin System and Atheromatous Renal Artery Stenosis. Hypertension
34: 1097-1100
[Abstract][Full Text]
Verdecchia, P., Reboldi, G., Schillaci, G., Borgioni, C., Ciucci, A., Telera, M. P., Santeusanio, F., Porcellati, C., Brunetti, P.
(1999). Circulating Insulin and Insulin Growth Factor-1 Are Independent Determinants of Left Ventricular Mass and Geometry in Essential Hypertension. Circulation
100: 1802-1807
[Abstract][Full Text]
Danser, A.H.J., Schunkert, H.
(1999). Renin-Angiotensin System and Blood Pressure. Circulation
100
: 85e-e86
[Full Text]
Okamura, A., Ohishi, M., Rakugi, H., Katsuya, T., Yanagitani, Y., Takiuchi, S., Taniyama, Y., Moriguchi, K., Ito, H., Higashino, Y., Fujii, K., Higaki, J., Ogihara, T., Higaki, J.
(1999). Pharmacogenetic Analysis of the Effect of Angiotensin-Converting Enzyme Inhibitor on Restenosis After Percutaneous Transluminal Coronary Angioplasty. ANGIOLOGY
50: 811-822
[Abstract]
Henrion, D., Benessiano, J., Philip, I., Vuillaumier-Barrot, S., Iglarz, M., Plantefeve, G., Chatel, D., Hvass, U., Durand, G., Desmonts, J.-M., Amouyel, P., Levy, B. I.
(1999). The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro. J Am Coll Cardiol
34: 830-836
[Abstract][Full Text]
Taylor, R. R., Mamotte, C. D. S., Fallon, K., van Bockxmeer, F. M.
(1999). Elite athletes and the gene for angiotensin-converting enzyme. J. Appl. Physiol.
87: 1035-1037
[Abstract][Full Text]
Anvari, A., Turel, Z., Schmidt, A., Yilmaz, N., Mayer, G., Huber, K., Schuster, E., Gottsauner-Wolf, M.
(1999). Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias. Cardiovasc Res
43: 879-883
[Abstract][Full Text]
Karjalainen, J., Kujala, U. M., Stolt, A., Mantysaari, M., Viitasalo, M., Kainulainen, K., Kontula, K.
(1999). Angiotensinogen gene M235T polymorphism predicts left ventricular hypertrophy in endurance athletes. J Am Coll Cardiol
34: 494-499
[Abstract][Full Text]
Djuric, D., Popovic, Z., Petrovic, J., Bojic, M., Djuric, D. M.
(1999). Age-Related Progressive Brachial Artery Endothelial Dysfunction Precedes the Changed Carotid and Left Ventricular Geometry in Healthy Humans. ANGIOLOGY
50: 555-561
[Abstract]
Pinto, Y. M, van Gilst, W. H
(1999). The ACE gene polymorphism: the good, the bad and the ugly. Cardiovasc Res
43: 23-24
[Full Text]
Perticone, F., Maio, R., Cosco, C., Ceravolo, R., Iacopino, S., Chello, M., Mastroroberto, P., Tramontano, D., Mattioli, P. L
(1999). Hypertensive left ventricular remodeling and ACE-gene polymorphism. Cardiovasc Res
43: 192-199
[Abstract][Full Text]
van SUYLEN, R. J., WOUTERS, E. F., PENNINGS, H. J., CHERIEX, E. C., van POL, P. E., AMBERGEN, A. W., VERMELIS, A.-M., DAEMEN, M. J.
(1999). The DD Genotype of the Angiotensin Converting Enzyme Gene Is Negatively Associated with Right Ventricular Hypertrophy In Male Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med.
159: 1791-1795
[Abstract][Full Text]
Komajda, M., Charron, P., Tesson, F.
(1999). Genetic aspects of heart failure. Eur J Heart Fail
1: 121-126
[Abstract][Full Text]
Lamb, H. J., Beyerbacht, H. P., van der Laarse, A., Stoel, B. C., Doornbos, J., van der Wall, E. E., de Roos, A.
(1999). Diastolic Dysfunction in Hypertensive Heart Disease Is Associated With Altered Myocardial Metabolism. Circulation
99: 2261-2267
[Abstract][Full Text]
Schunkert, H., Brockel, U., Hengstenberg, C., Luchner, A., Muscholl, M. W., Kurzidim, K., Kuch, B., Doring, A., Riegger, G.u. A. J., Hense, H.-W.
(1999). Familial predisposition of left ventricular hypertrophy. J Am Coll Cardiol
33: 1685-1691
[Abstract][Full Text]
Blackshear, J. L., Pearce, L. A., Hart, R. G., Zabalgoitia, M., Labovitz, A., Asinger, R. W., Halperin, J. L.
(1999). Aortic Plaque in Atrial Fibrillation : Prevalence, Predictors, and Thromboembolic Implications. Stroke
30: 834-840
[Abstract][Full Text]
Phillips, R. A., Krakoff, L. R., Dunaif, A., Finegood, D. T., Gorlin, R., Shimabukuro, S.
(1998). Relation among Left Ventricular Mass, Insulin Resistance, and Blood Pressure in Nonobese Subjects. J. Clin. Endocrinol. Metab.
83: 4284-4288
[Abstract][Full Text]
Yoshioka, T., Xu, Y.-x., Yoshida, H., Shiraga, H., Muraki, T., Ito, K.
(1998). Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schonlein purpura nephritis. Arch. Dis. Child.
79: 394-399
[Abstract][Full Text]
Alvarez, R., Reguero, J. R, Batalla, A., Iglesias-Cubero, G., Cortina, A., Alvarez, V., Coto, E.
(1998). Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphisms: association with early coronary disease. Cardiovasc Res
40: 375-379
[Abstract][Full Text]
Girerd, X., Hanon, O., Mourad, J. J., Boutouyrie, P., Laurent, S., Jeunemaitre, X.
(1998). Lack of Association Between Renin-Angiotensin System, Gene Polymorphisms, and Wall Thickness of the Radial and Carotid Arteries. Hypertension
32: 579-583
[Abstract][Full Text]
Muscholl, M. W, Hense, H.-W, Bröckel, U., Döring, A., Riegger, G. A J, Schunkert, H.
(1998). Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey. BMJ
317: 565-570
[Abstract][Full Text]
Doevendans, P. A, J. Daemen, M., de Muinck, E. D, Smits, J. F
(1998). Cardiovascular phenotyping in mice. Cardiovasc Res
39: 34-49
[Abstract][Full Text]
Mayet, J., Chapman, N., Li, C. K.-C., Shahi, M., Poulter, N. R., Sever, P. S., Foale, R. A., Thom, S. A.McG.
(1998). Ethnic Differences in the Hypertensive Heart and 24-Hour Blood Pressure Profile. Hypertension
31: 1190-1194
[Abstract][Full Text]
Perticone, F., Ceravolo, R., Maio, R., Ventura, G., Zingone, A., Perrotti, N., Mattioli, P. L.
(1998). Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Endothelium-Dependent Vasodilation in Never Treated Hypertensive Patients. Hypertension
31: 900-905
[Abstract][Full Text]
Kupari, M., Hautanen, A., Lankinen, L., Koskinen, P., Virolainen, J., Nikkila, H., White, P. C.
(1998). Associations Between Human Aldosterone Synthase (CYP11B2) Gene Polymorphisms and Left Ventricular Size, Mass, and Function. Circulation
97: 569-575
[Abstract][Full Text]
Post, W. S., Larson, M. G., Myers, R. H., Galderisi, M., Levy, D.
(1997). Heritability of Left Ventricular Mass : The Framingham Heart Study. Hypertension
30: 1025-1028
[Abstract][Full Text]
Hibi, K., Ishigami, T., Kimura, K., Nakao, M., Iwamoto, T., Tamura, K., Nemoto, T., Shimizu, T., Mochida, Y., Ochiai, H., Umemura, S., Ishii, M.
(1997). Angiotensin-Converting Enzyme Gene Polymorphism Adds Risk for the Severity of Coronary Atherosclerosis in Smokers. Hypertension
30: 574-579
[Abstract][Full Text]
TOMITA, H., INA, Y., SUGIURA, Y., SATO, S., KAWAGUCHI, H., MORISHITA, M., YAMAMOTO, M., UEDA, R.
(1997). Polymorphism in the Angiotensin-Converting Enzyme (ACE) Gene and Sarcoidosis. Am. J. Respir. Crit. Care Med.
156: 255-259
[Abstract][Full Text]
Agerholm-Larsen, B., Nordestgaard, B. G., Steffensen, R., Sorensen, T. I.A., Jensen, G., Tybjærg-Hansen, A.
(1997). ACE Gene Polymorphism: Ischemic Heart Disease and Longevity in 10 150 Individuals: A Case-Referent and Retrospective Cohort Study Based on the Copenhagen City Heart Study. Circulation
95: 2358-2367
[Abstract][Full Text]
Rossi, G. P., Sacchetto, A., Pavan, E., Palatini, P., Graniero, G. R., Canali, C., Pessina, A. C.
(1997). Remodeling of the Left Ventricle in Primary Aldosteronism Due to Conn's Adenoma. Circulation
95: 1471-1478
[Abstract][Full Text]
Muller, D. N., Bohlender, J., Hilgers, K. F., Dragun, D., Costerousse, O., Menard, J., Luft, F. C.
(1997). Vascular Angiotensin-Converting Enzyme Expression Regulates Local Angiotensin II. Hypertension
29: 98-104
[Abstract][Full Text]
Busjahn, A., Knoblauch, H., Knoblauch, M., Bohlender, J., Menz, M., Faulhaber, H.-D., Becker, A., Schuster, H., Luft, F. C.
(1997). Angiotensin-Converting Enzyme and Angiotensinogen Gene Polymorphisms, Plasma Levels, Cardiac Dimensions A Twin Study: A Twin Study. Hypertension
29: 165-170
[Abstract][Full Text]
Cambien, F., Tiret, L., Cheung, B., Lindpaintner, K., Larson, M. G., Wilson, A. F.
(1996). Absence of Association or Genetic Linkage between the Angiotensin-Converting-Enzyme Gene and Left Ventricular Mass. NEJM
335: 1070-1071
[Full Text]
Maeda, Y., Ikeda, U., Ebata, H., Hojo, Y., Seino, Y., Hayashi, Y., Kuroki, S., Shimada, K.
(1996). Angiotensin-Converting Enzyme Gene Polymorphism in Hypertensive Individuals With Parental History of Stroke. Stroke
27: 1521-1523
[Abstract][Full Text]
Singer, D. R.J., Missouris, C. G., Jeffery, S.
(1996). Angiotensin-Converting Enzyme Gene Polymorphism: What to Do About All the Confusion?. Circulation
94: 236-239
[Full Text]
Badenhop, R. F., Wang, X. L., Wilcken, D. E.L.
(1996). Association Between an Angiotensinogen Microsatellite Marker in Children and Coronary Events in Their Grandparents. Circulation
93: 2092-2096
[Abstract][Full Text]
Nakata, Y., Katsuya, T., Rakugi, H., Takami, S., Ohishi, M., Kamino, K., Higaki, J., Tabuchi, Y., Kumahara, Y., Miki, T., Ogihara, T.
(1996). Polymorphism of the Apolipoprotein E and Angiotensin-Converting Enzyme Genes in Japanese Subjects With Silent Myocardial Ischemia. Hypertension
27: 1205-1209
[Abstract][Full Text]
Schmieder, R. E., Martus, P., Klingbeil, A.
(1996). Reversal of Left Ventricular Hypertrophy in Essential Hypertension: A Meta-analysis of Randomized Double-blind Studies. JAMA
275: 1507-1513
[Abstract]
Lindpaintner, K., Lee, M., Larson, M. G., Rao, V. S., Pfeffer, M. A., Ordovas, J. M., Schaefer, E. J., Wilson, A. F., Wilson, P. W.F., Vasan, R. S., Myers, R. H., Levy, D.
(1996). Absence of Association or Genetic Linkage between the Angiotensin-Converting-Enzyme Gene and Left Ventricular Mass. NEJM
334: 1023-1028
[Abstract][Full Text]
Harrap, S. B., Dominiczak, A. F., Fraser, R., Lever, A. F., Morton, J. J., Foy, C. J., Watt, G. C.M.
(1996). Plasma Angiotensin II, Predisposition to Hypertension, and Left Ventricular Size in Healthy Young Adults. Circulation
93: 1148-1154
[Abstract][Full Text]
Rotimi, C., Puras, A., Cooper, R., McFarlane-Anderson, N., Forrester, T., Ogunbiyi, O., Morrison Ryk Ward, L.
(1996). Polymorphisms of Renin-Angiotensin Genes Among Nigerians, Jamaicans, and African Americans. Hypertension
27: 558-563
[Abstract][Full Text]
Wang, X.L., McCredie, R.M., Wilcken, D.E.L.
(1996). Genotype Distribution of Angiotensin-Converting Enzyme Polymorphism in Australian Healthy and Coronary Populations and Relevance to Myocardial Infarction and Coronary Artery Disease. Arterioscler. Thromb. Vasc. Bio.
16: 115-119
[Abstract][Full Text]
Bloem, L. J., Manatunga, A. K., Pratt, J. H.
(1996). Racial Difference in the Relationship of an Angiotensin I–Converting Enzyme Gene Polymorphism to Serum Angiotensin I– Converting Enzyme Activity. Hypertension
27: 62-66
[Abstract][Full Text]
Perez, N. G., Alvarez, B. V., Camilion de Hurtado, M. C., Cingolani, H. E.
(1995). pHi Regulation in Myocardium of the Spontaneously Hypertensive Rat : Compensated Enhanced Activity of the Na+-H+ Exchanger. Circ. Res.
77: 1192-1200
[Abstract][Full Text]
Schieken, R. M.
(1995). Large Hearts in Children : Biology or Disease?. Circulation
92: 3156-3157
[Full Text]
Kreutz, R., Hubner, N., Ganten, D., Lindpaintner, K.
(1995). Genetic Linkage of the ACE Gene to Plasma Angiotensin-Converting Enzyme Activity but Not to Blood Pressure : A Quantitative Trait Locus Confers Identical Complex Phenotypes in Human and Rat Hypertension. Circulation
92: 2381-2384
[Abstract][Full Text]
Previous
