Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension

doi:10.1016/j.numecd.2008.12.007

Nutrition, Metabolism and Cardiovascular Diseases

Volume 19, Issue 9, November 2009, Pages 646-653

https://doi.org/10.1016/j.numecd.2008.12.007 Get rights and content

Abstract

Background and aim

Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography.

Methods and results

The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis.

Conclusions

Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, and has been recognized as the hepatic expression of metabolic syndrome [1], [2]. Insulin resistance is the essential requirement for the accumulation of hepatocellular fat [3], [4], and subjects with NAFLD are at risk of developing cardiovascular disease through insulin-resistance related mechanisms [5], [6]. Arterial hypertension also is referred as an insulin resistant state, and insulin resistance may substantially contribute to the cardiovascular risk in this disorder [7], [8]. We recently reported [9] a high prevalence of NAFLD, associated with insulin resistance and low adiponectin, a fat-derived protein with positive effects on insulin sensitivity and cardiovascular function [10], [11], in a hypertensive population without major metabolic abnormalities. Such study confirmed previous observations in unselected hypertensive cohorts [12], [13].

Several reports, in which liver function and morphology were not investigated, have shown an association of insulin resistance and/or low adiponectin levels with cardiac abnormalities in healthy subjects or in hypertensive patients [14], [15], [16], [17]. To our knowledge, only one published study on normotensive patients with documented NAFLD has indicated a major role of factors associated with insulin resistance in the development of cardiac abnormalities [18].

The aim of our study was to investigate in essential hypertension, in a population of never-treated hypertensive patients without risk factors for fatty liver disease, the relationship between NAFLD, metabolic parameters, and left ventricular morphology and function.

Section snippets

Patients

In this observational cross-sectional study, 86 newly diagnosed never-treated patients with essential hypertension were considered. They were consecutively seen, within a larger essential hypertensive population (more than 1000 patients), at our three hospital-based specialized hypertension outpatient clinics over the past 12 months. Patients were first selected according to the following criteria: 1) age 18–65 years; 2) grade 1–2 hypertension, according to the criteria of the European Society

Results

Non-alcoholic fatty liver disease was detected overall in 48 out of 86 patients, i.e., 55.8% of our hypertensive patients. The distribution of ultrasound grading of NAFLD showed a higher prevalence of mild (n = 26, 54.2%) and moderate (n = 20, 41.6%) grade, while the severe degree of steatosis was present in 2 patients only. Clinical, endocrine-metabolic, and main cardiac parameters of hypertensive patients without and with NAFLD are shown in Table 1. The two groups of patients were similar as

Discussion

This study has demonstrated for the first time that hypertensive patients with NAFLD have a higher prevalence of LV diastolic dysfunction than those without fatty liver changes at ultrasonography. Goland et al. [18] have previously investigated by echocardiography the cardiac structure and function in normotensive individuals with NAFLD, reporting a slight increase in LV mass and a markedly impaired LV diastolic function. However, subjects included in that study had obesity and/or

Disclosures

The authors have no conflicts of interest.

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Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD.
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In one study, no differences in clinical or laboratory parameters could be demonstrated in PCOS patients compared with matched controls, but PCOS patients had more histological NASH on liver biopsy (44.0% versus 20.8%) and independent predictors of histological NASH in PCOS patients included elevated AST, high triglycerides, and small amount of alcohol consumption [36]. Taken together, lower oestradiol and higher androgen levels are associated with NAFLD in PCOS patients [26,34,36], and insulin resistance is an important contributing factor [26] and hallmark [31] of NAFLD. A Chinese study not only confirmed that NAFLD was more prevalence in PCOS than in controls (32.9% versus 18.5%), but PCOS patients with NAFLD also had significantly lower luteinizing hormone than those without NAFLD, and the prevalence and severity of NAFLD increased with BMI [28].
Elevated liver enzyme levels can sometimes be encountered in asymptomatic pregnant women. Similar to non-pregnant subjects, women with elevated gamma glutamyltransferase or alanine aminotransferase in early pregnancy have increased risk of subsequent complications, especially gestational diabetes mellitus. In non-pregnant subjects, the commonest cause of abnormal liver function currently is non-alcoholic fatty liver disease. Risk factors include obesity, diabetes, and the metabolic syndrome. It can progress to hepatocellular carcinoma through the development of steatohepatitis, and has become the leading cause for liver transplantation in women. Found in as many as 16–18% of pregnant women, it is associated with an increased risk of pregnancy complications and abnormal foetal growth, which predisposes the offspring to the same problem subsequently. This condition probably explains the majority of the cases of “idiopathic” abnormal liver function in pregnancy, and should be looked out for in high-risk women owing to its implications on their long-term health outcome.
Association between diastolic cardiac dysfunction and nonalcoholic fatty liver disease: A systematic review and meta-analysis
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Recent studies have suggested an association between nonalcoholic fatty liver disease (NAFLD) and diastolic cardiac dysfunction, although the results were inconsistent. This study was conducted to investigate this possible association.
A comprehensive literature review was conducted utilizing the MEDLINE and Embase databases from inception through May 2018 to identify all cross-sectional studies that compared the prevalence of diastolic cardiac dysfunction among patients with NAFLD to individuals without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird.
A total of 12 studies with 280,645 participants fulfilled the eligibility criteria and were included in the meta-analysis. There was a significant association between NAFLD and diastolic cardiac dysfunction with a pooled odds ratio (OR) of 2.02 (95% confidence interval (CI), 1.47–2.79; I² 89%). Subgroup analysis based on the country of origin continued to demonstrate a significant association in subgroups of both Western and Eastern countries with pooled ORs of 1.76 (95% CI, 1.14–2.72; I² 85%) and 2.59 (95% CI, 1.42–4.69; I² 87%), respectively. Limitations included high between-study heterogeneity, lack of unified definition of diastolic dysfunction and presence of publication bias.
A significant association between diastolic cardiac dysfunction and NAFLD was observed in this meta-analysis. This observation could suggest the need for careful cardiovascular surveillance among patients with NAFLD.
Bidirectional association between nonalcoholic fatty liver disease and hypertension from the Dongfeng-Tongji cohort study
2018, Journal of the American Society of Hypertension
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Emerging evidence has shown a clear clustering of hypertension among patients with nonalcoholic fatty liver disease (NAFLD) and vice versa.1,2 Approximately 50% of hypertensive patients have NAFLD,3 and in contrast, the prevalence rates of fatty liver disease (FLD) among hypertensive patients were 30%–56%.4,5 Numerous studies have investigated the association between FLD and hypertension.5–7
The relation between nonalcoholic fatty liver disease (NAFLD) and hypertension is not fully understood. To examine the effect of the change in NAFLD status on the risk of incident hypertension, and vice versa, 6704 eligible hypertension-free subjects and 9328 NAFLD-free subjects from the Dongfeng-Tongji cohort study at baseline were enrolled in the study. Among the hypertension-free subjects, development and persistence of NAFLD were associated with an increased odds ratio (OR) for incident hypertension (OR: 1.49, 95% confidence interval [CI]: 1.26–1.76, P < .0001; OR: 1.50, 95% CI: 1.27–1.78, P < .0001). However, the resolution of NAFLD was not a risk factor for incident hypertension. Among the NAFLD-free subjects, the risk of new-emerging NAFLD was robust for hypertension status both in no-yes (OR: 1.45, CI: 1.23–1.71) and yes-yes (OR: 1.61, CI: 1.35–1.92). Moreover, stratified analysis by diabetes and overweight/obese for the risk of incident NAFLD showed that incident hypertension (no-yes) and persistent hypertension (yes-yes) were associated with risk of incident NAFLD in subjects without diabetes or overweight/obesity. In the overweight/obese participants, persistent hypertension (yes-yes) was a risk factor for incident NAFLD (OR: 1.29, 95% CI: 1.01–1.64, P = .0387). Conclusively, incidence and persistence of NAFLD are associated with increased risk of hypertension, and vice versa.
Nonalcoholic fatty liver disease and advanced fibrosis are associated with left ventricular diastolic dysfunction
2018, Atherosclerosis
Nonalcoholic fatty liver disease (NAFLD) may be associated with a wide spectrum of cardiac abnormalities, which share many metabolic risk factors. This study aimed to evaluate whether NAFLD is associated with left ventricular (LV) diastolic dysfunction independent of other classical risk factors.
A total of 3300 subjects (mean age, 54.1 years; 62.9% men), who underwent echocardiography and hepatic ultrasonography, were enrolled. LV diastolic dysfunction was diagnosed and graded using conventional and Doppler echocardiographic assessments. NAFLD was diagnosed by ultrasonographic findings without any evidence of significant alcohol consumption or viral hepatitis, other liver diseases, or medication provoking fatty liver. Advanced fibrosis was defined as having intermediate-high probability for advanced fibrosis using the NAFLD fibrosis score.
The prevalence of LV diastolic dysfunction was 35.1%. NAFLD had a higher prevalence and severity of LV diastolic dysfunction. The prevalence rates of LV diastolic dysfunction were significantly increased according to the NAFLD fibrosis grade (30.4% for no-NAFLD, 35.2% for NAFLD without advanced fibrosis and 57.4% for NAFLD with advanced fibrosis, p < 0.001). Multivariable analysis showed that NAFLD was associated with a 29% increase in the risk of diastolic dysfunction compared with controls (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.07–1.60). There was significant interaction between obesity (BMI < 25 kg/m² vs. ≥ 25 kg/m²) and advanced fibrosis for LV diastolic dysfunction. A significant, incrementally increased risk of diastolic dysfunction according to the fibrosis grade was more pronounced in the non-obese population [adjusted OR (95% CI), 1.40 (1.06–1.84) for NAFLD without advanced fibrosis, 1.44 (0.95–2.17) for NAFLD with advanced fibrosis vs. no NAFLD, P for trend = 0.022] compared with the obese population (p for trend = 0.081), independent of other well-defined risk factors.
NAFLD was associated with increased risk for LV diastolic dysfunction. In addition, an incrementally increased risk for LV diastolic dysfunction according to fibrosis grade was prominent in the non-obese population.
Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients
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Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake.
A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [¹⁸F]-fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram.
Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e’ ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e’ ratio was independently associated with hepatic fibrosis (standardized β = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e’ ratio was also significant (standardized β = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity).
Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by ¹⁸FDG-PET.
Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake.

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Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension

Abstract

Background and aim

Methods and results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Disclosures

Nutr Metab Cardiovasc Dis

J Am Coll Cardiol

J Am Coll Cardiol

Am J Hypertens

Am J Hypertens

Gastroenterology

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Hypertens

Am J Gastroenterol

J Am Coll Cardiol

J Am Coll Cardiol

J Hepatology

Am J Hypertens

Am J Med

GI epidemiology: non-alcoholic fatty liver disease

Aliment Pharmacol Ther

Liver diseases and metabolic syndrome

J Gastroenterol

Insulin resistance: a metabolic pathway to chronic liver disease

Hepatology

Liver fat in the metabolic syndrome

J Clin Endocrinol Metab

Non-alcoholic fatty liver disease, metabolic syndrome and the risk of cardiovascular disease: the plot thickens

Diabet Med

Insulin resistance in essential hypertension

N Engl J Med