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Original article

Normotensive offspring of hypertensive Nigerians have increased Left ventricular mass and abnormal geometric patterns

Normotensive offspring of hypertensive Nigerians have increased Left ventricular mass and abnormal geometric patterns

 

Philip Kolo1, Emmanuel Sanya1, James Ogunmodede1, Ayodele Omotoso1, Ayodele Soladoye2

 

1Department of Medicine, University of Ilorin Teaching Hospital, P.M.B. 1459, Ilorin, Nigeria, 2Department of Physiology, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria

 

 

&Corresponding author
Dr Kolo Philip Manma, Department of Medicine, University of Ilorin Teaching Hospital, P.M.B 1459, Ilorin, Nigeria

 

 

Background

Current approach to the management of systemic hypertension (SH) is early diagnosis and identification of individuals at risk through detection of early makers of the disease. The Writing Group of American Society of Hypertension considers left ventricular hypertrophy (LVH) as one of the early makers of hypertensive cardiovascular disease [1]. The presence of LVH in patients with SH is a strong and independent risk factor for future cardiovascular morbidity and mortality [2-3]. It is well known that normotensive OHP are at increased risk of developing SH later in life when compared with ONP [4]. However, previous studies particularly among Caucasians on cardiovascular anatomic alterations in individuals who have pedigree for SH showed inconsistent results [5-6]. These discrepancies are probably due to selection criteria adopted with respect to the age and body weight of the subjects. On the other hand, it has been suggested that alterations in left ventricular mass and or function may precede development of sustained elevation in blood pressure; and may be genetically determined [7]. In the Tecumseh Offspring Study [8] heredity was found to account for a small but definite proportion of variations of LVM and the predictive power of heredity of LVM was only second to that of the child?s height. Similarly, in the Framingham Heart Study [9], heredity was also found to explained small but discernible proportion of variations in LVM. The aim of the present study was to evaluate left ventricular structure in OHP to determine whether subclinical cardiovascular dysfunction exists before the development of overt hypertension.

 

 

Methods

A simple random sample (using random numbers) of patients who were hypertensive and attending Cardiovascular Clinic of the University of Ilorin Teaching Hospital, Ilorin was conducted. The selected patients were requested to bring one of their eligible children between the ages of 15-25 years for assessment (OHP group). The same procedure was employed to select age and sex-matched children without parental hypertension (ONP) from Medical Outpatient Department to serve as controls. Ethical approval was obtained from the Ethics and Research Committee of the hospital and informed consent was obtained from each participant.

 

All individuals who were pregnant, on cardio active drugs, had cardio-pulmonary disease; and those with organic heart murmur and renal bruit were not eligible to participate. Similarly, those with structural heart disease and poor echocardiographic windows were excluded from the study. A thorough history to exclude cardiovascular disease in the participants was taken and anthropometric parameters, blood pressure and other relevant clinical examination were performed on all subjects. Blood pressure was measured at the left arm in a comfortable position after about 10 minutes rest using an appropriate cuff. However, if the blood pressure was equal or greater than 10mmHg at the right arm, the latter blood pressure was used as the blood pressure of the subjects. An average of three measurements was used as the blood pressure. Individuals with blood pressure ≥ 140/90 mmHg or on anti-hypertensive drugs were also excluded. Electrocardiogram was done in standard position and subsequently echocardiogram. A long parasternal 2D guided M - mode echocardiogram was done and measurement taken according to the recommendations of the American Society of Echocardiography (ASE) (Schiller et al, 1989) [10]. Parameters recorded included: LV internal dimension in diastole (LVIDd), LV internal dimension in systole (LVIDs), interventricular septal thickness in diastole (IVSd), interventricular septal thickness in systole (IVSs), posterior wall thickness in diastole (PWd), posterior wall thickness in systole (PWs), LV ejection fraction (EF) and fractional shortening (FS). Others include right ventricular dimension in diastole (RVd), aortic dimension (AOD) and left atrial dimension (LAD). LV mass (LVM) was calculated using the formula [11]: 0.8 × (1.04 ×((LVIDd + IVSd + PWd)3-(LVIDd)3) ) + 0.6. Left ventricular mass index (LVMI) was determined using formula: LVM/BSA, where BSA is the body surface area.Relative wall thickness (RWT) was calculated by the formula [12]: 2 × PWd/LVIDd. The pattern of LV remodelling was determined using LVMI and RWT. Increased RWT was present if RWT was ≥0.4512. LV geometric pattern was classified using RWT and LVMI as follows: Normal geometry = normal LVMI and RWT; Concentric remodelling= normal LVMI and RWT ≥0.45; Eccentric LV hypertrophy= increased LVMI and RWT <0.45; Concentric LV hypertrophy= increased LVMI and RWT ≥0.45

 

Statiscal analysis

 

Statistical analysis was performed using the SPSS Version 15 and numerical values were presented as mean ± standard deviation. Student t-test was used to compare means of continuous variables while chi-square test was used to compare means of proportions. Test of correlation was done using the Pearson?s correlation method. Stepwise regression analysis using 0.05 as entry probability and 0.10 as removal probability was used to determine predictors of LVM. A statistically significant association was taken at P<0.05

 

 

Results

The demographic characteristics of study participants are presented in Table 1. Sixty-five normotensive OHP with 65-age and sex-matched normotensive ONP were studied. They consisted of 18 (27.7%) females and 47 (72.3%) males in each group and their ages ranged from 15 to 25 years. The mean age of OHP was similar to that of ONP group (p>0.05). The anthropometric parameters showed that the body mass index, waist and hip circumference were similar in the two groups. Twenty-two (33.8%) subjects had history of hypertension in their fathers, 29 (44.6%) in mothers and 14 (21.5%) in both parents. The mean systolic and diastolic blood pressures though higher in OHP than ONP group, the difference did not reach statistical significance. Parameters of right ventricular and left ventricular dimensions are showed in Table 2. The right ventricular dimension in diastole, LVIDd and LVIDs; LAD and AOD were similar between the subjects and controls. However, the mean PWd in OHP was higher (p<0.001) than that of ONP group. Similarly, LVM, LVMI and RWT were significantly increased in the subjects than in controls (p<0.01, <0.01 and 0.001 respectively). On the other hand, parameters of left ventricular systolic function (ejection fraction and fractional shortening) were similar between the two groups. Left ventricular geometric patterns are shown in Figure 1. The incidence of abnormal left ventricular geometric patterns was significantly higher (p<0.01) in subjects than controls. In the subjects, SBP, DBP, waist and hip circumference as well as ECG voltage criteria correlated positively with LVMI while negative correlation was observed between LVMI and left ventricular ejection fraction (Table 3). Only waist circumference was independently associated with LVMI (Mean square=3724.339, F=20.745, P<0.001) in the patients.

 

 

Discussion

The main purpose of the present study was to evaluate left ventricular structure in normotensive OHP with the aim of detecting early abnormalities (if any) preceding onset of SH. The results showed that the LVMI as well as PWd were significantly higher in OHP than ONP (p<0.001 and 0.01 respectively). Similarly, prevalence of abnormal left ventricular geometric pattern was higher in the OHP compared with ONP (Figure 1). These results further confirm the findings of previous studies which demonstrated increased LVM in normotensive OHP against ONP [13-14]. On the other hand, our results contrast that of Jalal et al [15] and Graetinger et al [16] who did not find significant difference in LVM between the two groups. However, it is significant to note that our patients were older than those evaluated by Jalal et al [15] but similar in age to offspring of Dutch Hypertension and Offspring Study [17]. Therefore, age does appear to be an important factor in the expression of LVM phenotypes in OHP and; it is possible that difference in LVM and left ventricular structure may not be apparent at younger age group (<18 years) as alluded to by Jalal et al. Although, the clinical impact of left ventricular hypertrophy on morbidity and mortality is well known in cardiovascular diseases in adults, nevertheless, the origin of increased LVM and its clinical significance is still debated in OHP. Some investigators have suggested that increased LVM may be a forerunner of hypertension and future cardiovascular events in these individuals [18-19]. The association of obesity with LVM in normotensive children has been demonstrated in some studies [20]. Our study showed that the waist circumference correlated positively with LVMI; and at the same time an independent predictor of LVMI. Waist circumference reflects the visceral distribution of fat and may be more important than the body mass index in this group of individuals [21].

 

Published observations had also shown mean 24-hour ambulatory systolic and diastolic blood pressure values to be an important determinant of LVM in hypertensive children and OHP [22-23]. In our study, both mean systolic and diastolic blood pressures were similar in the two groups. On the other hand, the role of genetic contribution to the variations in LVM has been recognized and these variations are thought to be co-inherited with risk of hypertension in genetically predisposed individual [24]. However, the selection of our subjects was based on parental and offspring?s blood pressures but not on parental LVM. Therefore, the influence of parental LVM on variations of LVM in the offspring was not demonstrated in the present study.

 

Assessment of left ventricular geometry further refined risk associated with LVH in individuals with systemic hypertension [25]. This study showed higher incidence of abnormal left ventricular geometric patterns in the subjects compared with the controls. The presence of abnormal left ventricular geometry in normotensive offspring of hypertensive parents suggests that alterations in left ventricular structure may also have genetic basis. This is supported by a recent study by Lam et al [26] which showed familiar aggregation of left ventricular geometry in a two generation community-based sample.

 

The results of the present study also showed that the parameters of left ventricular systolic function at rest were similar between the OHP and ONP groups. This is not surprising because prior investigations have shown that even in hypertensive individuals, alterations in the indices of left ventricular systolic function occur late in the course of the disease [27].

 

 

Conclusion

In conclusion, normotensive offspring of hypertensive parents have alterations in left ventricular mass and geometry even before they have sustained elevation of blood pressure. OHP should be considered as a special group which needs early dietary adjustment and lifestyles modification in order to prevent future cardiovascular events.

 

 

Acknowledgments

We acknowledge assistance received from staff of the Cardiopulmonary Unit, University of Ilorin Teaching Hospital during echocardiographic examination on the subjects.

 

 

Competing interests

The authors declare that they have no competing interests.

 

 

Authors’ contributions

Dr Kolo was involved in the design of the work, acquisition and analysis of data; drafting of the manuscript and corresponding author. Dr Sanya was involved in data analysis and interpretation. Dr Ogunmodede was part of data acquisition team and analysis. Prof Omotoso guided data acquisition and interpretation while Prof Soladoye was involved in design and data interpretation. All authors reviewed and approved the final manuscript.

 

 

Tables and figures

Table 1: Clinical characteristics of the study group

Table 2: Echocardiographic parameters of the subjects and controls

Table 3: Correlates of Left ventricular mass index in normotensive offspring of hypertensive parents

Figure 1: Left ventricular geometric patterns in the subjects and controls. Normal: Normal-geometry; Con rem: Concentric remodeling; Ecc LVH: Eccentric Left Ventricular Hypertrophy; Con LVH: Concentric left Ventricular Hypertrophy; Abnormal: Abnormal geometry

 

 

References

  1. Giles TD, Berk BC, Black HR, Cohn JN, Kostis JB, Izzo JL, Weber MA. Expanding the definition and classification of hypertension: On behalf of the Hypertension Writing Group, American Society of Hypertension. Journal of Clinical Hypertension. 2005; 7: 505-511. This article on PubMed

  2. Levy D, Garrison RJ, Savage DD, Kannel WB, Casteelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990; 322: 1561-1566. This article on PubMed

  3. Cipriano C, Gosse P, Bemurat L, Mas D, Lemetayer P, N?Tela G, Clementy J. Prognostic value of left ventricular mass and its evolution during treatment in the bordeaux cohort of hypertensive patients. Am J Hypertens. 2001; 14: 524-529. This article on PubMed

  4. Skov K, Eiskjaer H, Hansen HE, Madsen JK, Kvist S, Mulvany MJ. Treatment of young subjects at high familiar risk of future hypertension with an angiotensin receptor blocker. Hypertension. 2007; 50: 89-95. This article on PubMed

  5. Allemann Y, Aeschbacher B, Zwvssig P, Ferrari P, Hopf M, Shaw S, Gurtner HP, et al. Left ventricular structure and determinants in normotensive offsprings of essential hypertensive parents. J Hypertens. 1992;10:1257-1264. This article on PubMed

  6. Galderisi M, Celentano A, Tammaro P, Mureddu GF, Garofalo M, de Simone G, de Divitiis O. Ambulatory blood pressure monitoring in offspring of hypertensive patients Relation to left ventricular structure and function. Am J Hypertens. 1993; 6: 114-120. This article on PubMed

  7. Kapuku GK, Ge D, Vemulapalli S, Harshdield GA, Treiber FA, Snieder H. Change of genetic determinants of left ventricular structure in adolescence: longitudinal evidence from the Georgia cardiovascular twin study. Am J Hypertens. 2008 Jul;21(7):799-805. This article on PubMed

  8. Palatini P, Krause L, Amerena J, Nesbitt S, Majahalme S, Tikhonoff V, Valentini M, et al. Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study. J Hypertens. 2001; 19: 1217-1222. This article on PubMed

  9. Post WS, Larson MG, Myers RH, Galderisi M, Levy D. Heritability of left ventricular mass: the Framingham Heart Study. Hypertension. 1997; 30: 1025-1028. This article on PubMed

  10. Schiller NB, Shah PM, Crawford M. recommendations for quantification of the left ventricle by two-dimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on Quantification of two-dimensional echocardiogram. J Am Soc Echocardiogr. 1989 Sep-Oct;2(5):358-67. This article on PubMed

  11. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986; 57:450-458. This article on PubMed

  12. Savage DD, Garrison RJ, Kannel WB, Levy D, Anderson SJ, Stokes J. The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study. Circulation. 1987 Jan;75(1 Pt 2):I26-33. This article on PubMed

  13. Jaiswal P, Mahajan S, Diwan S, Acharya S Wanjari A. Left ventricular mass in offspring of hypertensive parents: does it predict the future?. The Internet Journal of Cardiovascular Research. 2009; volume 7 number 1

  14. Radice M, Alii C, Avanzini F. Left ventricular structure and function in normotensive adolescents with a genetic predisposition to hypertension. Am Heart J. 1986;111:115-120. This article on PubMed

  15. Jalal S, Rauoof MA, Khan KA, Hamid S, Waheed A, Jan VM. Left ventricular mass and functions in normotensive offspring of hypertensive parents: an echocardiographic study. J Assoc Physicians India. 2009; 57:389-392. This article on PubMed

  16. Graettinger WF, Neutel JM, Smith DHG, Weber MA. Left ventricular diastolic filling alterations in normotensive young adults with a family history of systemic hypertension. Am J Cardiol. 1991;68:51-56. This article on PubMed

  17. van Hooft IM, Grobbee DE, Waal-Manning HJ, Hofman A. Hemodynamic characteristics of the early phase of primary hypertension The Dutch Hypertension and Offspring Study. Circulation. 1993 Apr;87(4):1100-6.. This article on PubMed

  18. Mahajan S, Diwan S, Wanjari A, Acharya S. Left Ventricular Mass ? Forerunner of Future Cardiovascular Morbidity in Young Healthy Population?. The Internet Journal of Cardiology. 2009; 7(2)

  19. Mahoney LT, Schieken RM, Clarke WR, Lauer RM. Left ventricular mass and exercise responses predict future blood pressure The muscatine study. Hypertension. 1988;12: 206-213. This article on PubMed

  20. Friberg P, Allansdotter-Johnson A, Ambring A, Ahl R, Arheden H, Framme J. Increased left ventricular mass in obese adolescents. Eur Heart J. 2004; 25: 987-992. This article on PubMed

  21. Leung LCK, Sung RYT, So HK, Wong SN, Lee KW, Lee KP. Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents: waist circumference predicts hypertension, exercise decreases risk. Arch Dis Child. 2011 Sep;96(9):804-9. This article on PubMed

  22. Sorof JM, Cardwell G, Franco K, Portman RJ. Ambulatory blood pressure and left ventricular mass index in hypertensive children. Hypertension. 2002; 39: 903-908. This article on PubMed

  23. Richey PA, DiSessa TG, Hastings MC, Somes GW, Alpert BS, Jones DP. Ambulatory Blood Pressure and Increased Left Ventricular Mass in Children at Risk for Hypertension. The Journal of Pediatrics. 2008; 152: 343-348. This article on PubMed

  24. Harshfield GA, Grim CE, Hwang C, Savage DD, Anderson SJ. Genetic and environmental influences on echocardiographically determined left ventricular mass in black twins. Am J Hypertens. 1990;3:538-543. This article on PubMed

  25. Muiesan ML, Salvetti M, Monteduro C, Bonzi B, Paini A, Viola S. Left ventricular geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension. 2004; 43: 731-738. This article on PubMed

  26. Lam CSP, Liu X, Yang Q, Larson MG, Pencina MJ, Aragam J, Redfield MM, et al. Familial Aggregation of Left Ventricular Geometry and Association with Parental Heart Failure: The Framingham Heart Study. Circ Cardiovasc Genet. 2010; 3: 492-8. This article on PubMed

  27. Slama M, Susic D, Varagic J, Frohlich ED. Diastolic dysfunction in hypertension. Curr Opin Cardiol. 2002;17: 368-373. This article on PubMed