Is left ventricular hypertrophy a low-level inflammatory state? A population-based cohort study

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Abstract

Background and Aims

Cross-sectional studies have shown that chronic sub-clinical inflammation is associated with left ventricular hypertrophy (LVH), but results are conflicting. We investigated the association between baseline LVH and high-sensitivity C-reactive protein (CRP) values, both cross-sectionally and after a six-year-follow-up, in a population-based cohort (n = 1564) and a subgroup from this cohort (n = 515), without obesity, diabetes, metabolic syndrome or any drugs.

Methods and Results

ECG tracings at baseline were interpreted according to the Cornell voltage-duration product criteria: 166/1564 subjects (10.6%) showed LVH. Patients with baseline LVH showed increased BMI, waist circumference, blood pressure, and a worse metabolic pattern. Their CRP values both at baseline and at follow-up were almost two-fold higher than in patients without LVH. Similar results were found in the healthier sub-sample. In a multiple regression model, CRP at follow-up was directly associated with baseline LVH (expressed as Cornell voltage-duration product) in the whole cohort (β = 0.0003; 95%CI 0.0002–0.0006; p < 0.001) and in the sub-sample (β = 0.0003; 0.0002–0.0004; p < 0.001), after adjusting for age, sex, BMI, waist circumference, smoking, exercise levels, blood pressure and baseline CRP values.

Conclusion

Baseline LVH, which is associated with systemic inflammation, predicts increased CRP values at follow-up, independently of cardiovascular and metabolic risk factors, both in a population-based cohort and a healthier sub-sample. The inflammatory consequences of LVH might be an intriguing subject for further researches.

Introduction

Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular morbidity and mortality [1], [2]. Pathophysiological mechanisms underlying these associations might be abnormalities in the coronary vessels [3], or platelets [4], a prothrombotic condition [5], endothelial dysfunction, and systemic inflammation, which could lead to accelerated atherosclerosis [6], [7]. Furthermore, LVH is a manifestation of target organ damage from coexistent risk factors, such as hypertension, overweight, and diabetes.

Previous studies have shown that LVH was cross-sectionally associated with fibrinogen, C-reactive protein (CRP) and soluble tumor necrosis factor (TNF) receptor values [7], [8], [9], [10], [11], [12], [13], [14]. It has been hypothesized that LVH itself may be an inflammatory state in animal [15] and human studies [10], [16]. Ventricular wall stress produces an increase in cytokine levels, which may induce and amplify the inflammatory response [17].

Most human studies were performed in selected cohorts (patients with resistant hypertension, chronic hemodialysis, or type 2 diabetes) or were cross-sectional [7], [8], [9], [10], [11], [12], [13], [14]; the latter were therefore unable to derive a temporal or causal relationship between inflammatory markers and LVH. Furthermore, the results of these studies are conflicting, because in multivariable-adjusted models, the relation is no longer significant [11], [12], [13]. Thus, the association of LVH with inflammation might be mediated by clinical risk factors that are themselves related to an inflammatory state.

Electrocardiogram (ECG) patterns of LVH were found to be associated with cardiovascular risk [18], [19]. The ECG is a simple, non-invasive, low-cost, and reproducible test. In addition, its accuracy in diagnosing LVH was recently confirmed in obese patients [20]. In particular, the Cornell voltage-duration product [21], and the Perugia criteria [22], when compared with echocardiography, give the best sensitivity and specificity for LVH diagnosis and have a better prognostic value in predicting cardiovascular risk [20], [21], [22], [23], [24], [25].

In this study, we hypothesized that LVH is a pro-inflammatory state and we investigated the possible association between baseline LVH and high-sensitivity C-reactive protein (CRP) values both cross-sectionally and after a mean six-year-follow-up in a population-based cohort and a normal-weight subgroup from this cohort, without diabetes, metabolic syndrome, or any other known concurrent medical condition requiring drugs.

Section snippets

Study population

The Caucasian patients (n = 1877) aged 45–64 years of six family physicians were invited to participate in a metabolic screening in 2001–2003. These subjects were representative of the Local Health Units of the province of Asti (North-western Italy); 1658 (88.3%) subjects agreed to participate and provided written informed consent, while 219 patients declined. Both participants and non-participants were similar to the resident population of a corresponding age range, with respect to the

Results

The mean follow-up time was 6.1 ± 0.34 years. LVH was identified at baseline in 166/1564 subjects (10.6%). Patients with baseline LVH showed increased values for age, BMI, waist circumference, blood pressure, and percentage of males, and had a significantly worse metabolic pattern, both at baseline and after follow-up (Table 1). CRP values both at baseline and after follow-up were almost two-fold higher in patients with baseline LVH.

In the sub-sample without MS, age, BMI, waist circumference,

Discussion

Both in a population-based cohort and in a healthier sub-sample from this cohort, baseline LVH is associated with systemic inflammation, and its presence predicts increased CRP values after a six-year-follow-up, independently of cardiovascular risk factors and waist circumference.

LVH is a strong predictor of adverse cardiovascular outcome [1], [2]. The inter-relationship between the activation of systemic inflammation and LVH might be one of the mechanisms implied, given the well known

Conclusion

In a population-based cohort without clinically overt cardiovascular disease and in a sub-sample without drug therapy, MS, obesity and diabetes, baseline LVH is prospectively associated with increased CRP values. Screening patients for LVH, therefore, might be useful not only for distinguishing high-cardiovascular risk individuals, independently of associated co-morbidities as already known [1], [2], but for identifying those who are predisposed to a pro-inflammatory state, too.

Although there

Conflict of interest

None declared.

Acknowledgment

This work was supported by a grant: “Progetto di Ricerca Sanitaria Finalizzata, Regione Piemonte, 2008” [DD n. 12,14.01.2008]. The funding source had no involvement in study design, the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.

References (37)

  • P.M. Okin et al.

    Electrocardiographic identification of left ventricular hypertrophy: test performance in relation to definition of hypertrophy and presence of obesity

    J Am Coll Cardiol

    (1996)
  • H.L. Taylor et al.

    Questionnaire for the assessment of leisure time physical activities

    J Chronic Dis

    (1978)
  • S. Bo et al.

    Dietary magnesium and fiber intake, inflammatory and metabolic parameters in middle-aged subjects from a population-based cohort

    Am J Clin Nutr

    (2006)
  • D. Levy et al.

    Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study

    N Engl J Med

    (1990)
  • P. Verdecchia et al.

    Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension

    Circulation

    (2001)
  • B. Schwartzkopff et al.

    Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension

    Circulation

    (1993)
  • R. Ross

    Atherosclerosis: an inflammatory disease

    N Engl J Med

    (1999)
  • V. Palmieri et al.

    Fibrinogen and preclinical echocardiographic target organ damage. The strong heart study

    Hypertension

    (2001)
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