Summary
The determinants of left ventricular mass in normal control subjects and subjects with non-insulindependent diabetes (NIDDM) are ill-defined. We therefore recorded M-mode and pulsed Doppler echocardiograms and 24-h ambulatory blood pressure in 57 normotensive subjects, 34 with NIDDM and 23 matched non-diabetic control subjects. Measurements of erythrocyte sodium-lithium countertransport, plasma angiotensin II, plasma and platelet catecholamines and fasting plasma insulin were also made. Six control subjects (26%) and 15 diabetic subjects (44%) had some degree of left ventricular hypertrophy. Subjects with left ventricular hypertrophy (n=21) had an elevated mean rate of sodium-lithium countertransport (0.40±0.13 vs 0.31±0.09 mmol·l−1 ·h−1; p<0.01), parallel differences being observed in both the diabetic and control groups. Twelve of the subjects with left ventricular hypertrophy (57%) had elevated rates of sodium-lithium counter-transport compared to only seven (19%) of those without (p<0.05). There was no consistent difference between those with and without left ventricular hypertrophy in any other clinical or biochemical variable. Multivariate analysis, with the presence or absence of left ventricular hypertrophy as the dependent variable, demonstrated that the maximal rate of sodium-lithium countertransport was the only variable that independently contributed to left ventricular hypertrophy (partial r=0.35; F 1.55=7.74; p = 0.007). This study demonstrates for the first time an association between left ventricular hypertrophy and erythrocyte membrane cation transport that is independent of hypertension, is present in both diabetic and non-diabetic groups, and may represent a link between elevated rates of membrane sodium transport and cardiovascular risk.
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Abbreviations
- Na-Li CT:
-
Sodium-lithium countertransport
- LVH:
-
left ventricular hypertrophy
- AER:
-
urinary albumin excretion rate
References
Casale PN, Devereux RB, Milner M et al. (1986) Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 105: 173–178
Silberberg JS, Barre PE, Prichard SS, Sniderman AD (1989) Impact of left ventricular hypertrophy on survival in end stage renal disease. Kidney Int 36: 286–290
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP (1989) Left ventricular mass and incidence of coronary heart disease in an elderly cohort. Ann Intern Med 79: 291–293
Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH (1991) Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 114: 345–352
Rosengren A, Welin L, Tsipogianni A, Wilhelmsen L (1989) Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study. BMJ 299: 1127–1131
Galderisi M, Anderson KM, Wilson PWF, Levy D (1991) Echocardiographic evidence for the existence of distinct diabetic cardiomyopathy. Am J Cardiol 68: 85–89
Savage DD, Levy D, Dannenberg AL, Garrison RJ, Castelli WP (1990) Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity (The Framingham study). Am J Cardiol 65: 371–376
Devereux RB, Pickering TG, Cody RJ, Laragh JH (1987) Relation of renin angiotensin system to left ventricular hypertrophy and function in experimental and human hypertension. J Clin Hypertension 3: 87–103
Corea L, Bentivoglio M, Verdecchia P, Motolese M (1982) Left ventricular wall thickness and plasma catecholamines in borderline and stable essential hypertension. Eur Heart J 3: 164–170
Sasson Z, Rasooly Y, Bhesania T, Rasooly T (1993) Insulin resistance is an important determinant of left ventricular mass in the obese. Circulation 88: 1431–1436
Yap L, Arrazola A, Soria F, Diez J (1989) Is there increased cardiovascular risk in essential hypertensive patients with abnormal kinetics of red blood cell sodium-lithium countertransport. J Hypertension 7: 667–673
WHO Study Group (1985) Diabetes mellitus. WHO Technical Report Series. No 727. Geneva
White WB (1990) Predicting hypertensive heart disease via non-invasive methodology: relationship between ambulatory blood pressure and cardiac indices derived by echocardiography and radionuclide ventriculography. J Hypertension 8: s113-s118
Devereux RB, Campo E, Sachs I, Reicheck N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57: 450–458
Levy D, Savage DD, Garrison RJ et al. (1987) Echocardiographic criteria for left ventricular hypertrophy: the Framingham heart study. Am J Cardiol 67: 956–960
Rokey R, Kuo LC, Zoghbi WA, Limacher MC, Quinones MA (1985) Determination of parameters of left ventricular diastolic filling with pulsed Doppler echocardiography: comparison with cineangiography. Circulation 71: 543–550
Friedewald WT, Levy RI, Frederickson DS (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 18: 499–502
Mohamed-Ali V, Yudkin JS (1992) An end point amplified enzymo immunoassay (IEMA) specific for human insulin. Clin Sci 82 [Suppl 27]: 48
Dusterdieck G, McElwee G (1971) Estimation of angiotensin II concentration in human plasma by radioimmunoassay. Some applications to physiological and clinical states. Eur J Clin Invest 2: 32–38
Carstensen E, Yudkin JS (1994) Platelet catecholamine concentrations after short term stress in normal subjects. Clin Sci 86: 35–41
Foyle WJ, Drury PL (1991) Reduction of Li-Na countertransport by physiological levels of insulin in vitro. J Hypertens 9: 713–717
Canessa M, Adragna N, Solomon HS, Connolly TM, Tocheson DC (1980) Increased sodium-lithium countertransport in red cells of patients with essential hypertension. New Eng J Med 302: 772–776
Gould MM, Mohamed-Ali V, Goubet SA, Yudkin JS, Haines AP (1993) Microalbuminuria: associations with height and sex in non-diabetic subjects. BMJ 306: 240–242
Levy D, Anderson KM, Savage DD et al. (1988) Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. Ann Intern Med 108: 7–13
Gambardella S, Frontoni S, Spallone V et al. (1993) Increased left ventricular mass in normotensive diabetic patients with autonomic neuropathy. Am J Hypertension 6: 97–102
Nosadini R, Semplicini A, Fioretto P et al. (1991) Sodium-lithium counter transport and cardiorenal abnormalities in essential hypertension. Hypertension 18: 191–198
Saito T, Kai N, Yamamoto N et al. (1993) Cardiovascular response and red cell membrane sodium transport in hypertensive cardiac hypertrophy. J Hum Hyper 7: 485–489
Weder AB, Schork NJ, Krause L, Julius S (1991) Red blood cell lithium-sodium transport in the Tecumseh blood pressure study. Hypertension 17: 652–660
Schieken RM, Clarke WR, Lauer RM (1981) Left ventricular hypertrophy in children with blood pressures in the upper quintile of the distribution. The Muscatine study. Hypertension 3: 669–675
Rutherford PA, Thomas TH, Wilkinson R (1992) Erythrocyte sodium-lithium countertransport: clinically useful, pathologically instructive or just phenomenology? Clin Sci 82: 341–352
Trevisan R, Cipollina MR, Duner E et al. (1993) Increased alkalinising effect of insulin and angiotensin II on fibroblasts from hypertensive and microalbuminuric type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36 [Suppl 1] A34 (Abstract)
England BK, Chastain JL, Mitch WE (1991) Abnormalities in protein synthesis and degradation induced by extracellular pH in BC3111 myocytes. Am J Physiol 260: C277-C281
Maly K, Hochleitner BW, Grunicke H (1990) Interrelationship between growth factor-induced activation of the Na-H antiporter and mobilisation of intracellular calcium in N1H3T3 fibroblasts. Biochem Biophys Res Commun 167: 1206–1213
Thibonnier M, Bayer AL, Simonson MS, Douglas JG (1992) Effects of amiloride analogues on AVP-binding and activation of V1 receptor expressing cells. Am J Physiol 262: E76-E86
Semplicini A, Lusiani L, Marzola M et al. (1992) Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin dependent diabetics. Eur J Clin Invest 22: 254–259
Mahoney LT, Schieken RM, Clarke WR, Lauer RM (1988) Left ventricular hypertrophy and exercise responses predict future blood pressure. The Muscatine Study. Hypertension 65: 1192–1197
DeSimone G, Devereux RB, Schlussel V et al. (1990) Echocardiographic left ventricular mass predicts risk of developing subsequent borderline hypertension. J Am Coll Cardiol 15: 14–18
Nielsen JR, Oxhoj H (1985) Echocardiographic variables in progeny of hypertensive and normotensive parents. Acta Med Scand 693 [Suppl]: 61–64
Boerwinkle E (1986) Analysis of the distribution of erythrocyte sodium lithium countertransport in a sample representative of the general population. Genet Epidemiol 3: 365–378
Simpson P (1983) Norephinephrine stimulated hypertrophy of cultured rat myocardial cell is an alpha-adrenergic response. J Clin Invest 72: 732–738
Griffin SA et al. (1991) Angiotensin II causes vascular hypertrophy by a non-pressor mechanism. Hypertension 17: 626–635
Sierra A, Coca A, Pare JC et al. (1993) Erythrocyte ion fluxes in essential hypertensive patients with left ventricular hypertrophy. Circulation 88: 1628–1633
Trevisan M, Ostrow D, Cooper RS, Sempos C, Stamler J (1984) Sex and race differences in sodium-lithium countertransport and red cell sodium concentration. Am J Epidemiol 120: 537–541
Paillole C, Dahan M, Paycha F et al. (1989) Prevalence and significance of left ventricular filling abnormalities determined by Doppler echocardiography in young type 1 (insulin dependent) diabetic patients. Am J Cardiol 64: 1010–1016
Genda A, Mizuno S, Nunoda S et al. (1986) Clinical studies on diabetic myocardial disease using exercise testing with myocardial scintigraphy and endomyocardial disease. Clin Cardiol 9: 375–382
Nunoda S, Genda A, Sugihara N, Nakayama A, Mizone S, Takeda R (1985) Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus. Heart and Vessels 1: 43–47
Lynch M, Gammage MD, Lamb P, Nattrass M, Pentecost BL (1994) Acute myocardial infarction in the thrombolytic era. Diabet Med 11: 162–166
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Sampson, M.J., Denver, E., Foyle, W.J. et al. Association between left ventricular hypertrophy and erythrocyte sodium-lithium exchange in normotensive subjects with and without NIDDM. Diabetologia 38, 454–460 (1995). https://doi.org/10.1007/BF00410283
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DOI: https://doi.org/10.1007/BF00410283