Impaired left ventricular diastolic function during isometric exercise in asymptomatic patients with hyperlipidaemia

https://doi.org/10.1016/j.ijcard.2003.06.005Get rights and content

Abstract

Background: Left ventricular (LV) diastolic dysfunction is an early sign, and may be more sensitive indicator, of ischaemic heart disease (IHD) than systolic dysfunction. Methods: LV diastolic function was assessed during isometric exercise (IME) in 37 consecutive normotensive hyperlipidaemics (LIP), without cardiac history or symptoms. Each patient underwent a stress ECG test and 2-D echo and Doppler cardiography. During the latter, transmitral flow at rest and at peak standardised IME using handgrip was studied. From the tracings, the E/A (peak velocity of the early/atrial components), the contribution of atrial systole to LV filling (ACF), the deceleration time (DT) of the E wave and the isovolumic relaxation time (IVRT) were calculated. Results were compared to 37 age-matched normal healthy volunteers (NOR). Results: Resting E/A was not different between NOR and the LIP. A significant reduction in E/A with IME was observed in LIP but not in NOR. Impaired LV filling (shown by E/A<1) was demonstrated in five patients (13%) at rest and in 20 patients (54%) at peak IME. All NOR had E/A>1 suggesting normal LV filling. Fifteen of the 30 patients with negative stress ECG test demonstrated LV diastolic dysfunction. ACF was higher in LIP than NOR and increased significantly (P<0.005) by 23% during IME. DT and IVRT in LIP were not different from NOR. In neither NOR nor LIP, were the LV diastolic functional parameters related to gender, smoking habit or levels of total cholesterol, LDL- or HDL-cholesterol or triglycerides. Conclusion: The prevalence of LV diastolic dysfunction in asymptomatic patients with hyperlipidaemia despite a negative stress ECG test may be evidence of early underlying pre-clinical myocardial ischaemia.

Introduction

Hyperlipidaemia is a recognised major but modifiable risk factor for the development and progression of coronary heart disease and other atherosclerotic conditions [1], [2]. The benefit of reducing cholesterol level in patients with and without established coronary artery disease (CAD) on the prevention of ischaemic manifestations has been well documented [3], [4], [5].

One of the recognised features of ischaemic heart disease is left ventricular (LV) diastolic dysfunction [6], [7], which, precedes systolic dysfunction in the natural history of ischaemic heart disease [7]. Even in the absence of systolic LV dysfunction, diastolic dysfunction of the LV can cause the clinical syndrome of congestive heart failure [8], [9]. Diminished exercise capacity in patients with congestive heart failure and normal systolic LV function has been reported to be the result of impaired diastolic function [10]. As many as one third of patients with heart failure have normal systolic LV function suggesting that diastolic dysfunction is the main pathophysiological mechanism [8], [11]. It is, therefore, important to identify LV diastolic dysfunction at an early stage even prior to the occurrence of systolic dysfunction or appearance of symptoms.

In normal subjects, isometric exercise (IME) has a positive inotropic effect on the heart by causing a rise in systolic and diastolic blood pressure, a small rise in systemic vascular resistance and a moderate rise in heart rate [12], [13]. Similar effects of IME have been reported in patients with hypertension and patients with ischaemic heart disease [14], [15]. IME has been shown to induce LV diastolic dysfunction as determined by Doppler echocardiography in non-diabetic patients with exertional angina and significant coronary artery lesions who have normal LV diastolic function at rest [16]. On the other hand, in healthy individuals or in patients with atypical chest pain but normal coronary arteriogram IME does not induce LV diastolic function [16].

To our knowledge, LV diastolic function has not yet been studied in asymptomatic subjects with hyperlipidaemia. In this report we examined LV diastolic function both at rest and during IME in patients with hyperlipidaemia whom otherwise had no symptoms related to their cardiovascular system.

Section snippets

Patients and methods

Thirty seven consecutive normotensive patients (20 males and 17 females) with hyperlipidaemia were consecutively recruited from the Lipid Clinic. All had a normal resting ECG, normal fasting blood glucose level and no symptoms or history related to the cardiovascular system. Their ages ranged from 34 to 72 years (mean 54.5±9.8). Other demographic features are shown in Table 1. Twenty eight patients (14 males and 14 females) had type IIa hyperlipidaemia while the other nine were classified as

Results

At rest, no significant difference was found in the E/A between the patients and the volunteers. At peak IME the E/A was significantly lower in the patients than the NOR. This was mainly the result of a higher peak velocity of the active flow resulting from atrial contraction (A) against a lower peak velocity for the early passive flow (E) in the patients than the NOR at peak IME (Table 2). Accordingly, the contribution of the flow due to atrial contraction to the LV filling (ACF) in the

Discussion

We have shown for the first time that LV diastolic function is impaired in asymptomatic normotensive subjects with hypercholesterolaemia but normal fasting glucose level. The diastolic LV abnormalities were revealed by Doppler echocardiography only during IME. These abnormalities were independent of the levels of either total cholesterol, LDL- or HDL-cholesterol and were irrespective of patient's age, gender, family history of cardiovascular disease or smoking habit. Hence hyperlipidaemia is

References (51)

  • S.P Marso

    Optimising the diabetic formulary: beyond aspirin and insulin

    J. Am. Coll. Cardiol.

    (2002)
  • R Detrano et al.

    The diagnostic accuracy of exercise electrocardiogram, a meta-analysis of 22 years of research

    Prog. Cardiovasc. Dis.

    (1989)
  • R Detrano et al.

    Exercise-induced ST segment depression in the diagnosis of multivessel coronary disease. A meta-analysis

    J. Am. Coll. Cardiol.

    (1989)
  • A Rozanski et al.

    The efficacy of cardiovascular nuclear medicine exercise studies

    Semin. Nucl. Med.

    (1987)
  • M Rodriguez-Porcel et al.

    Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous Scavenging activity

    J. Am. Coll. Cardiol.

    (2001)
  • T.D Wang et al.

    The effects of dyslipidemia on left ventricular systolic function in patients with stable angina pectoris

    Atherosclerosis

    (1999)
  • A.M Salmasi et al.

    Age-associated changes in left ventricular diastolic function are related to increasing left ventricular mass

    Am. J. Hypertens.

    (2003)
  • S.M Grundy

    Cholesterol and heart disease; a new era

    J. Am. Med. Assoc.

    (1986)
  • J Simes et al.

    Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project

    Eur. Heart J.

    (2002)
  • Randomised trial of cholesterol lowering lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

    Lancet

    (1994)
  • J Shepherd et al.

    Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group

    New Engl. J. Med.

    (1995)
  • R.O Bonow et al.

    Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography

    Circulation

    (1981)
  • J.T Stewart et al.

    Left atrial and left ventricular diastolic function during acute myocardial infarction

    Br. Heart J.

    (1992)
  • A Dodek et al.

    Pulmonary edema in coronary artery disease without cardiomegaly: paradox of the stiff heart

    New Engl. J. Med.

    (1972)
  • R.J Vecht

    The grip test: a simple method for the assessment of left ventricular performance

    Eur. J. Cardiol.

    (1976)
  • Cited by (15)

    • The Natural History of Patients with Isolated Metabolic Syndrome

      2016, Mayo Clinic Proceedings
      Citation Excerpt :

      To quantitate the LV mass, standard formulas based on M-mode measurement of diastolic dimension and wall thickness were used. Pulsed-wave Doppler examination of mitral flow (before and during Valsalva maneuver) and pulmonary venous inflow, as well as by Doppler tissue imaging of the mitral annulus, was used to measure diastolic dysfunction as previously described.5 A 4-point ordinal scale was created to grade diastolic dysfunction as follows: (1) normal; (2) mild diastolic dysfunction, defined as abnormal relaxation without increased LV end-diastolic filling pressure (peak early (E) to peak late [atrial] (A) diastolic filling velocity ratio <0.75); (3) moderate or “pseudonormal” diastolic dysfunction, defined as abnormal relaxation with increased LV end-diastolic filling pressure (E/A ratio of 0.75-1.5, deceleration time >140 ms, and 2 other Doppler indices of elevated LV end-diastolic filling pressure); and (4) severe diastolic dysfunction, defined as advanced reduction in compliance with restrictive filling (E/A ratio >1.5, deceleration time <140 ms, and Doppler indices of elevated LV end-diastolic filling pressure).

    • Effects of a personalized nine weeks intermittent exercise working program on left ventricle filling function in middle-aged women with mild diastolic dysfunction

      2014, European Geriatric Medicine
      Citation Excerpt :

      Accordingly, both central (cardiac) and peripheral (muscles and vessels) factors contribute to the beneficial effects of exercise training [51]. In the view of our results, we can hypothesize that when cardiac function is nearly normal, and particularly with a normal E-Ea ratio (which strongly and negatively correlated with exercise capacity) [33], training-induced improvement mainly results from peripheral factors such as enhanced vasodilatation and/or increased muscle mitochondrial oxidative capacity [52,53]. Despite interesting results, our study has some limitation.

    • Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

      2011, Atherosclerosis
      Citation Excerpt :

      An inverse correlation between total and LDL cholesterol levels and diastolic function by standard echocardiographic parameters was first noted in hypertensive postmenopausal women [28]. Subsequently, it was observed that diastolic function is impaired in normotensive hyperlipidemic patients [29]. In a more controlled, experimental setting, Huang et al. were able to show that feeding rabbits a high-cholesterol diet leads to an impairment in calcium uptake into the sarcoplasmic reticulum within four days and impairment in systolic shortening and diastolic relaxation rates after ten weeks [30].

    • Regional Diastolic Contour Abnormalities During Contrast Stress Echocardiography: Improved Detection of Coronary Artery Disease

      2008, Journal of the American Society of Echocardiography
      Citation Excerpt :

      Although RDCAs were associated strongly with ischemic heart disease, multifactorial origins of diastolic alterations cannot be excluded. The incidence of diastolic dysfunction increases with age,12,30,31 and several studies associate diastolic dysfunction with LV hypertrophy, diabetes mellitus, or hyperlipidemia.32-35 Indeed, the same risk factors for development of CAD also affect diastolic function before development of angiographically significant stenosis; therefore, the specificity of the findings for detection of clinically significant epicardial coronary artery stenosis may be limited.

    • Early impairment of left ventricular function in hypercholesterolemia and its reversibility after short term treatment with rosuvastatin. A preliminary echocardiographic study

      2008, Atherosclerosis
      Citation Excerpt :

      Echocardiographic techniques have been used to study the consequences of hypercholesterolemia on cardiac function. Salmasi et al. [8] found no significant difference in E/A ratio measured by pulsed wave Doppler between hypercholesterolemic subjects and controls at rest, but a significantly lower E/A ratio at peak isometric exercise in the patient group. Recently, the effect of statins-therapy on left ventricular function has been evaluated by tissue Doppler imaging [9].

    View all citing articles on Scopus
    View full text