Left Ventricular Hypertrophy
Insulin resistance and hyperinsulemia appear prevalently in hypertensive individuals. The question
might be asked: what is the role of insulin resistance in the risk profile and pathogenesis of left
ventricular hypertrophy (LVH)? An association between insulin resistance syndrome and the presence of
LVH has been demonstrated. (1,2) Even stronger findings are presented by Lind
(3) whose analysis yielded only insulin resistance as significantly
associated with LVH, and it accounted for 43% of the variability of left ventricular mass.
Whether it is the insulin resistance or the hyperinsulenimia that is the true factor in the development
of LVH is not clear. A study of insulin resistance, glucose metabolism, and left ventricular mass,
found that insulin resistance but not glucose intolerance and hyperinsulinemia were responsible for
accelerating the pathogenesis of LVH and carotid wall thickening (4)
A Finnish study of the activity of insulin in the cardiac muscle is and excellent clue to the mechanism
of action of this phenomenon (5). They examined glucose uptake rates in the
muscle, and observed that in hypertensives, whole-body and femoral glucose uptake rates were lower
than the controls. The uptake in the myocardium, however, was elevated compared to the controls.
The authors suggest that insulin-stimulated glucose uptake is supressed in the skeletal muscle, but
up-regulated in the myocardium in proportion to cardiac workload in essential hypertension.
This could indicate that glucose uptake may be an indicator of risk in distinguishing those at risk from
insulin-resistance-associated LVH in the preclinical stages. One difficulty with some of the studies that
attempt to characterize relationships among clinical paramaters in the population with small
sample sizes. One such study observed 29 nonobese hypertensive patients(6).
They concluded from their data that insulin resistance is no a factor in either 24-hour blood pressure,
or left ventricular mass. Their data showed no correlation of peak insulin levels after glucose
challenge with ambulatory BP, or left ventricular mass index. This study was, however, carried out
in nonobese patients, and this may account for the equivocal findings.
Another study in support of the insulin resistance model is that of Lind et al. who demonstrated
that in addition to the morphologic characteristics of the left ventricle, actual diastolic dysfunction
was related to decreased insulin sensitivity(6).
They concluded from their data that LVH and its associated
diastolic dysfunction are indeed associated with the insulin resistance syndrome.
Proposal
I propose the following research project: Examine the role of salt sensitivity in the appearance
and progression of LVH. It has been postulated (7) that certain patients
would be ill-served by the removal of salt from their diets. Furthermore, these patients would be at
risk for 'rebound hypertension' and potentially exacerbation of their existing or nascent LVH. I propose
a cohort study of preclinical hypertensives with demonstrated abnormalities of glucose uptake in the
myocardium. This group,compared to a suitable control, could be administered either a low salt diet, or perhaps
the Mediterranian Diet. Changes in left ventricular mass, glucose uptake, insulin, and blood pressure
could be observed to determine if there are indeed individuals in whom salt prohibition could result
in increased risk for left ventricular hypertrophy and its associated sequelae.
References
1. Sasson Z, Rasooly Y, Bhesania T, Rasooly I. Insulin resistance is an important determinant of left
ventricular mass in the obese. Circulation 88(4/1):1431-1436, 1993.
2. Marcus R, Krause L, Weder AB, Dominguez-Meja A, Schork NJ, Julius S. Sex-specific determinants
of increased left ventricular mass in the Tecumseh Blood Pressure Study. Circulation90(2):928-36, 1994.
3. Lind L, Andersson PE, Andren B, Hanni A, Lithell HO. Left ventricular hypertrophy in hypertension
is associated with the insulin resistance matabolic syndrome. Journal of Hypertension 13(4):433-8, 1995.
4. Kamide K, Nagano M, Nakano N, Yo Y, Kobayashi R, Rakugi H, Higaki J, Ohihara T. Insulin resistance
and cardiovascular complications in patients with essential hypertension. American Journal of Hypertension
9(12/1):1165-71, 1996.
5. Nuutila P, Maki M, Laine H, Knuuti MJ, Ruotsalainen U, Luotolahti M, Haaparanta M, Solin O, Jula A, Koivisto VA. et.al.
Insulin action on heart and skeletal muscle glucose uptake in essential hypertension. Journal of
Clinical Investigation96(2):1003-1009, 1995.
6. Costa CH, Batista MC, Moises VA, Kohlmann NB, Ribeiro AB, Zanella MT. Serum insulin levels,
24-hour blood pressure profile, and left ventricular mass in nonobese hypertensive patients. Hypertension
26(6/2):1085-8, 1995.
7. Working notes: Epidemiology of Cardiovascular Disease Medical University of South Carolina, Charleston SC.
Professor: Dr. Daniel Lackland, Fall 1998.