Development of new fatty liver, or resolution of existing fatty liver, over five years of follow-up, and risk of incident hypertension

Background & Aims

Approximately 50% of hypertensive patients have non-alcoholic fatty liver disease (NAFLD), but whether change in fatty liver status over time modifies risk of developing hypertension is uncertain. Our aim was to determine whether a change in fatty liver status (either development of new fatty liver, or resolution of existing fatty liver) over five years modified risk of incident hypertension at five year follow-up.

Methods

11,448 patients without hypertension were examined at baseline and at five year follow-up, using a retrospective cohort study design. Fatty liver status (absent or present) was assessed at baseline and follow-up using standard ultrasound criteria. Adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for incident hypertension at follow-up were estimated controlling for potential confounders, compared to the reference group (patients who did not have fatty liver at either baseline or follow-up).

Results

911 patients developed incident hypertension. Incident fatty liver developed during follow-up in 1418 patients and fatty liver at baseline resolved during follow-up in 684 patients. Developing incident fatty liver was associated with incident hypertension, even after adjustment for multiple confounders (aOR = 1.60 (95% CI 1.30, 1.96; p <0.001). Further adjustment for change in body mass index between baseline and follow-up only slightly attenuated this association (aOR = 1.36 (95% CI 1.10, 1.67; p = 0.004). With resolution of fatty liver at follow-up, risk of incident hypertension was not different from the reference group (aOR = 1.21 (95% CI 0.90, 1.63; p = 0.21).

Conclusions

Development of incident fatty liver is associated with increased risk of hypertension.

Introduction

Approximately 50% of hypertensive patients have non-alcoholic fatty liver disease (NAFLD) [1], [2] and in cross sectional studies increased blood pressure is associated with NAFLD in patients with increased alanine transaminase concentrations [3]. Although the mechanism explaining the association between NAFLD and increased blood pressure is uncertain, it has recently been demonstrated that there is general thickening of the left ventricular wall in NAFLD, independent of changes in left ventricular mass [4]. Increased wall thickness is associated with reduced longitudinal fiber shortening, which is indicative of left ventricular hypertrophy [5]. Hypertrophy of the cardiac wall may lead to the increased ventricular strain seen in NAFLD, both affecting the endocardium and entire wall, as a result of the altered geometry (reduced radius).

Although it is presently not known whether such changes underpin the association between increased blood pressure and NAFLD, it is also plausible that increased renin angiotensin system activity mediated by increased adipose tissue mass or altered renal function [6] could explain the increased prevalence of hypertension. For example many patients with NAFLD are overweight or obese and increasing evidence suggests that NAFLD is associated with chronic kidney disease (CKD) not only in a general population [7] but also in patients with both type 1 [8] and type 2 diabetes [9]. It is possible that common risk factors contribute to development of NAFLD, hypertension and to CVD. Since it is not known whether resolution of fatty liver, or development of new fatty liver, modifies risk of hypertension; the aim of our study was to determine whether a change in fatty liver status (either development of new fatty liver, or resolution of existing fatty liver over a five year period), were associated with incident hypertension at five year follow-up.