BIBLIOGRAPHY

LVM is affected by anthropometric indices such as weight, height, BMI and BSA but there is a lack of agreement in literature regarding which of these indices correlates best with LVM. Three studies^18,139,163 in children and adolescent found weight to be the best determinant of LVM. On the other hand other investigators found BMI a better determinant of LVM especially if obesity is present.45,164,165 Brandao et al ⁴⁴ and Devereux et al¹⁶⁶, found BSA to be the best determinant of LVM in adolescents and adults

arrived at a similar conclusion. In this study LVM correlated best with BSA, followed by weight and height, similar to the findings of Oladokun and Omokhodion^167. However, in this study only weight was found to be a determinant of LVM in a multiple regression analysis, suggesting that excess body weight may contribute to the development of excessive LVM and eventual LVH. The drawback of BSA as a determinant of LVM is that it could mask the presence of obesity and its effects on LVM. Indexing LVM to height^2.7 is now generally accepted as the most reliable way of correlating LVM with anthropometric indices and a value greater than 51g/m^2.7 is accepted as the diagnostic cut-off point for LVH.⁴³ This cut-off point is above the 99^th percentile for LVMI in normal children and adolescents and above this point LVM is considered excessive for body size and predicts increased morbidity.⁴³

5.8 LVM and Blood Pressure

Blood pressure especially SBP is known to have a close relationship with LVM, with larger LVM found in the upper quartiles of blood pressure curves. In this study, larger LVM and LVMI were in the upper quartiles of the SBP curve and less distinctly the DBP curve. This is similar to the findings of Dekkers et al⁵⁰ Hansen et al¹⁴⁰ and Schieken et al.^141. This relationship is biologically plausible

in that increased after load associated with elevation of blood pressure presents a stimulus for hypertrophy to reduce the peak systolic wall stress of the left ventricle.¹⁵⁸

Other studies have also shown that the SBP and to a lesser extent DBP are strong predictors of LVM.^15,37,163 In the Bogalusa Heart study, Urbina et al³⁷ found univariate associations between SBP and DBP and LVM but did not find blood pressure significant in a multivariate analysis that included anthropometric variables. In this present study univariate associations between SBP, DBP and LVM were found though the association between DBP and LVM was weaker. Regressional analysis involving SBP, DPB and weight showed that only weight and to a very minor extent SBP were determinants of LVM. This suggests that SBP might play some biological role in determining LVM and its role may be additive to that of weight. This is similar to the findings reported by de Simone et al¹⁶⁹ in adults.

5.9 LVM and Family History of Hypertension

In this study offsprings of hypertensives had a significantly larger LVM than the controls. This is in keeping with findings from other studies.^30,50,132

Furthermore the present study shows that maternal and paternal influences on LVM of offsprings are not the same. Offsprings of maternal hypertensives had larger LVM and LVMI than offsprings of paternal hypertensives. This is in keeping with findings from other offspring studies.^132,139 The difference between these subsets of parental hypertensives is possibly due to the fact that the left ventricular structural adaptation is highly dependent on mitochondrial metabolism and maximal aerobic power has been demonstrated to be under predominant maternal influence¹³⁹. Since mitochondrial genes are inherited matrilineally, offsprings of maternal hypertensives expectedly should have higher LVM and LVMI.

Intrauterine environment has also been shown to play a pivotal role in the development of the fetus and is predominantly determined by genetic and environmental factors linked to the mother¹³⁹. This may account for the higher LVM and LVMI of offsprings of maternal hypertensives. Besides according to the Barkers hypothesis harsh

intrauterine environment is a risk factor for the development of future cardiovascular disease.

Beyond genetic influences, it has been suggested that environmental factors can account for the close concordance between mothers and offsprings’ LVM. Children share the home environment with their mothers and to a lesser extent with their fathers, who are commonly involved in work outside the home. It has been suggested that this environmental factor may partly contribute to the close concordance between mothers and offsprings’ LVM¹³⁹. However this suggestion will not apply in situations where the mother is involved in long hours of work outside the home while the father stays more at home with the children or where both parents are involved in long hours of work outside the home as is the case in most homes in contemporary Nigeria. In this study the length of parental contact with the children was not examined.

Offsprings are thought to derive their genetic make-up in equal proportions from their fathers and mothers in line with the Mendelian hypothesis. Thus subjects in whom both parents are hypertensive were expected to have the largest LVM and LVMI. In this study however, these subset of subjects had high LVM and LVMI, which

were comparable with those whose mothers alone were hypertensive. This shortfall may be due to their number, which was comparatively smaller than subjects with maternal and paternal hypertension respectively. On the other hand, it might be possible that the paternal genetic contributions to LVM could be diluted by the presence of maternal genes that mediate the growth of LVM.

5.10 LVM and Echocardiographic Parameters

Echocardiographic parameters such as the IVS, PWT and RWT were significantly higher in the subjects. There was no significant difference in LV dimensions between subjects and controls. These findings are in agreement with previous studies.^44,132,139 Thus in this study increases in LVM are largely due to ventricular wall thickening.

Analysis of the LV geometry from this study showed that 55% of the subjects had normal geometry, 33% had concentric remodeling, 7%

had concentric hypertrophy and 5% had eccentric hypertrophy.

Schunkert et al¹⁷¹, studying familial predisposition to LVH in normotensive offsprings of hypertensives, obtained similar findings.

However, there was no case of eccentric hypertrophy in that study.

Family history of hypertension appears to contribute to the development of abnormal LV geometry.

5.11 Left Ventricular Hypertrophy

The prevalence of echocardiographic LVH in this study was 19%

which is close to values obtained in similar studies done in Caucasians, in which a prevalence rate of 26-32% was obtained.^18,20,145 However it is lower than the prevalence rate of between 65-72% in Americans of African ancestry.¹⁴⁵ This wide difference could be due to the size of the study population which was larger than that used in the present study. Secondly Americans of African ancestry are a hyper-selected group, whose genetic make-up may not be similar to those of core Africans. Also their genes may represent a hybrid of genetic influence from inter-racial marriages. Paucity of prevalence studies amongst Africans and Nigerians especially makes it difficult to compare data derived from this study.

The prevalence of LVH and abnormal LV geometric patterns was higher in males than in females. This gender difference possibly stems from the know fact that estrogen protects the females from LVH by down-regulating the expression of genes for LVH.⁴⁰ this may also explain the lower prevalence of abnormal forms of LV geometry in females. The prevalence of LVH was also higher in the older age group. Though this could be attributed to the progressive

increase in LVM with age, studies have shown that age as a determinant of LVH becomes weak in the presence of other determinants like weight and SBP.^160-162 Thus as individuals grow older their weights and SBP increase as well and could in addition explain part of the age-related increase in LVM and eventual LVH.

LVH was associated with higher SBP in this study. Previous studies have demonstrated the close relationship between LVM and SBP5,140,141,162 This relationship may be attributed to hypertrophic response to increased after-load to minimize systolic wall stress,¹⁵⁸ though genetic and neuro-humoral factors have also been implicated.

The prevalence of electrocardiographic LVH in this study was 27%

and 18% for the Sokolow-Lyon and Cornel voltage criteria respectively. These are comparable with values obtained by Mayosi et al¹⁴⁵ in which they got a prevalence of 39% and 23% for the Sokolow-Lyon and Cornel voltage criteria respectively. However Mayosi’s study was done in Caucasians. Dada et al¹⁷², studying the prevalence of LVH in adult Nigerian hypertensives found 48% and 28% prevalence of LVH using the Sokolow-Lyon and Cornel voltage criteria respectively. These values are higher than those obtained in

this present study. Age and population characteristics (BP levels) could account for these differences in prevalence.

This study further goes to confirm the known fact that electrocardiography is generally a poorly sensitive but highly specific tool for the diagnosis of LVH.¹⁷³ Of the 27 subjects who had LVH by the Sokolow-Lyon criteria only 11 were confirmed by echocardiography. Similarly echocardiography was able to confirm 7 of the 18 subjects who had LVH by the Cornel voltage criteria.

These yielded a sensitivity of 57.9% and 36.8% for the two criteria respectively. This pattern of sensitivity is comparable with the 51%

and 49% for both criteria obtained in African Americans recruited in the LIFE study.¹⁷⁴ However, the MAVI study,¹⁷³ an all-Caucasian study reported lower sensitivity values of 11.2% and 15.2% for both the Sokolow-Lyon and Cornel voltage criteria respectively. This difference could be genetic as it is known that blacks generate higher precordial voltages on ECG than whites⁶². In Nigeria, Katibi and Adenle,⁵⁷ Araoye⁶⁰ and Dada et al¹⁷² found the Sokolow-Lyon’s criteria to be highly sensitive, 90.5%, 80% and 70.55% respectively.

These studies were done in adult hypertensives and this probably explains the higher sensitivities relative to the one obtained in this present study. When compared with the MAVI¹⁷³ and LIFE¹⁷⁴

studies, both involving adult hypertensives, the Nigerian studies yielded higher sensitivities for the Sokolow-Lyon criteria probably due to genetic differences⁶².

The specificity values of the Sokolow-Lyon and Cornel voltage criteria from this study 78% and 84.7%. In the MAVI study,¹⁷³ a higher specificity of 91.1% was reported for the Sokolow-Lyon criteria while a specificity of 91.4%, comparable to the one obtained in this study was reported. However in the LIFE study,¹⁷⁴ the specificities for both criteria were 44% and 78%. These were lower than those reported in this study. The population characteristics of the study population could account for this difference. From this study the Cornel voltage criteria combines low sensitivity with high specificity and might possibly be a better screening tool for LVH than the Sokolow-Lyon criteria.

CHAPTER SIX

CONCLUSION, RECOMMENDATIONS AND LIMITATION

6.0 This study has been able to show that LVM is affected by family history of hypertension in addition to gender, age, anthropometric parameters and systolic blood pressure.

LVH and abnormalities of LV geometry may pre-date the development of clinically overt hypertension.

6.3.1 Specific Conclusions

(i) The strongest determinants of LVM are positive family history of hypertension, weight, age and systolic blood pressure.

(ii) LVH and abnormality of LV geometry may pre-date the development of clinically overt hypertension.

(iii) Males are at more risk of LVH and abnormal LV geometry than females.

(iv) Echocardiography remains superior to electrocardiography in the diagnosis of LVH even in adolescents.

6.4 RECOMMENDATIONS

(i) Maintenance of ideal body weight is encouraged since weight is a very strong predictor of LVM.

(ii) Offsprings of hypertensives may constitute a special risk population that should be closely followed up with periodic clinical and echocardiographic evaluation.

(iii) Echocardiography is recommended for these individuals when they have LVH on ECG since it combines very high sensitivity and specificity in diagnosing LVH. It is also invaluable in the evaluation of LV geometry.

(iv) More studies especially longitudinal studies should be carried out to truly ascertain the rate of growth of the left ventricle and the rate of change of the blood pressure.

6.5 LIMITATIONS OF THE STUDY

(i) It is known from longitudinal studies that LVM and SBP of offsprings of hypertensives track the highest percentiles and this peer-rank order is maintained over the years. This study being cross-sectional in design could not demonstrate this tracking and thus the rate of growth of the left ventricle and rate of increase in the SBP could not be studied.

(ii) The study population was modest in comparison with the other cited studies that involved very large study population.

Cost implication and limited time for this study made it difficult to recruit a very large number of individuals.

(iii) This study was not blinded. Thus researcher’s bias cannot be objectively ruled out.

REFERENCES

1. Casale PN, Devereux RB, Milner M, Zullo G: Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105:173-178.

2. 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.

3. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP: Left Ventricular Mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med 1989;

110:101-107.

4. Kannel WB, Dannenberg AL, Levy D. Population implications of Electrocardiographic left ventricular hypertrophy. Am J Cardiol 1987; 60:851-931.

5. deSimone G, Devereuex RB, Schlussel Y, Roman MJ, Alderman MH, Laragh JH. Echocardiographic left ventricular mass predicts risk of developing subsequent borderline hypertension. J Am Coll Cardiol 1990; 15: 160-165.

6. Mulvany MJ. Are vascular abnormalities a primary cause or secondary consequences of hypertension? Hypertension 1991; 18 [3 Suppl]: 52-7.

7. Gardin JM, Wagenknecht LE, Anton-Culver H, et al. Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. The CARDIA Study. Circulation 1995; 92:380-387.

8. Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. the Framingham Study.

Ann Intern Med 1988; 108:7-13.

9. Savage DD, Levy D, Dannenberg AL, Garrison RJ, Castelli WP.

Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity; the Framingham Study.

Am J Cardiol 1990; 65:371-376.

10. Manolio TA, Levy D, Garrison RJ, Castelli WP, Kannel WB. Relation of alcohol intake to left ventricular mass: the Framingham Study. J Am Coll Cardiol 1991; 17:717-721.

11. Liebson PR, Grandits G, Prineas R, et al. Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study [TOMHS]. Circulation 1993; 87:476-486.

12. Dekkers JC, Snieder H, Van den Oord EJCG, Treiber FA.

Moderators of blood pressure development from childhood to adulthood: a 10 year longitudinal study in African and European American Youth. J Pediatr 2002; 141:770-779.

13. Dekkers C, Treiber FA, Kapuku G, Van den Oord EJCG, Snieder H.

Growth of left ventricular mass in African American and European American Youth. Hypertension 2002; 39:943-951.

14. Bao W, Threefoot SA, Srinivasan SR, Berenson GS: Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertension 1995; 8:657-665.

15. Malcom DD, Burns TL, Mahoney LT, Lauer RM. Factors affecting the left ventricular mass in childhood: the Muscatine Study.

Pediatrics 1993; 92:703-709.

16. 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.

17. 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.

18. Garner C, Lecomte E, Visvikis S, Abergel E, Lathrop M, Soubrier F.

Genetic and environment influences on left ventricular mass: a family study. Hypertension 2000; 36:740-746.

19. Bielen E, Fagard R, Amery A. The inheritance of left ventricular structure and function assessed by imaging and Doppler echocardiography. Am Heart J 1991; 121:1743-1749.

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

21. Palatini P, Krause L, Amerena J, et al. Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study. J Hypertens 2001; 19:1217-1222.

22. World Health Report 1999: Making a difference Geneva. World Health Organization 1999.

23. Donnison C. O. Blood pressure in African nature. Lancet 1929; 1:6-8.

24. Omran AR: The epidemiologic transition: A theory of the epidemiology of population change. Milbank Mem Fund Q49:509-538, 1974.

25. Akinkugbe OO. World Epidemiology of Hypertension in Blacks. In:

Hall W. D; Saunde E., Shulman B. [editors] Year Book Medical Publishers, New York. 1985:3-16.

26. Akinkugbe OO. Non-Communicable Diseases in Nigeria. The next epidemics: Nigeria preparedness. Third Biennial Abayomi Bamidele Memorial Lecture. Nig J Clin Pract. 2000; 3:37-42.

27. Akinkugbe OO. Non-Communicable Diseases in Nigeria, Final Report of a National Survey, Lagos. Federal Ministry of Health and Social Services. 1997; 12-41.

28. WHO/ISH. Guidelines for the Management of Hypertension. J Hypertens 1999; 17:151-183.

29. Neutel JM, Smith DH, Graettinger WF et al. Heredity and Hypertension: Impact on metabolic characteristics. Am Heart J 1992; 124 [2]: 435-40.

30. Radice M, Alli C, Avanzini F, et al. Left ventricular structure and function in normotensive adolescents with a genetic predisposition to hypertension. Am Heart J 1986; 111:115-120.

31. Munger RG, Prineas RJ, Gomez – Marin O. Persistent elevation of blood pressure among children with a family history of hypertension:

the Minneapolis Children’s blood pressure study. J Hypertens 1988;

6 [Supply 1]: 107-109.

32. http://www.answers.com/topic/adolescent.feb112007.

33. Levy D, Savage DD, Garrison RJ, Anderson KM, Kannel WB, Castelli W. Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol 1987; 59:

956 - 960.

34. Devereux RB, Lutas EM, Casale PN, et al. Standardization of M-mode echocardiographic left ventricular anatomic measurements. J Am Coll Cardiol 1984; 4:1222-1230.

35. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH.

Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991; 114-345-352.

36. Daniels SR, Meyer RA, Liang Y, Bove KE. Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults. J Am Coll Cardiol 1988; 12:703-708.

37. Urbina EM, Gidding SS, Bao W, Pickoff AS, Berdusis K, Berenson GS. Effect of body size, ponderosity and blood pressure of left ventricular growth in children and young adults in the Bogalusa Heart Study. Circulation 1995; 91:2400-2406.

38. Himmelmann A, Svensson A, Hansson L. Influence of sex on blood pressure and left ventricular mass in adolescents: the Hypertension in Pregnancy Offspring Study. J Hum Hypertens 1994; 8:485-490.

39. de Simone G, Devereux RB, Daniels SR, Meyer RA: Gender differences in left ventricular growth. Hypertension 1995; 26: 979 – 983.

40. Cabral A, Vasquez E, Moyses M, Antonio A. Sex hormone modulation of ventricular hypertrophy in sinoaortic denervated rats.

Hypertension 1988; 11:93-97.

41. Malcom DD, Burns TL, Mahoney LT, Lauer RM. Factors affecting left ventricular mass in childhood: the Muscatine study. Pediatrics 1993; 92:703-709.

42. Daniels SR, Kimball TR, Morrison JA, et al. Indexing left ventricular mass to account for differences in body size in children and adolescents without cardiovascular disease. Am J Cardiol 1995;

76:699-701.

43. de Simone G, Devereux RB, Daniels SR, et al. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 1995; 25: 1056 – 1062.

44. Brandao AA, Pozzan R, Albanesi Filho FM, Brandao AP. Role of anthropometric indexes and blood pressure as determinants of left ventricular mass and geometry in adolescents: the Rio de Janeiro Study. Hypertension 1995; 26:1190-1194.

45. Daniels SR, Loggie JMH, Khoury P, Kimball TR. Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension. Circulation 1998; 97:1907-1922.

46. Schunkert H, Hense H, Holmes SR, et al. Association between a deletion polymorphism of the angiotensin-converting enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 330:1634-1638.

47. Gharavi AG, Liptowitz MS, Diamond JA et al: Deletion polymorphism of the angiotensin-converting enzyme gene is independently associated with left ventricular mass and geometric remodelling in systemic hypertension. Am J Cardiol 1996; 73:1315-1319.

48. Gump BB, Matthews DA. Modeling relationships among socioeconomic status, hostility, cardiovascular reactivity, and left ventricular mass in African American and white children. Health Psychol 1999; 18:140-145.

49. Cook BB, Treiber FA, Mensah G, Jindal M, Davis HC, Kapuku GK.

Family history of hypertension and left ventricular mass in youth:

possible mediating parameters. Am J Hypertens 2001; 14:351-356.

50. Dekkers JC, Treiber FA, Kapuku GK, Snieder H. Differential influence of family history of hypertension and premature myocardial infarction on systolic blood pressure and left ventricular mass trajectories in youth: Pediatrics 2003; [3]: 1387 – 1392.