Uncontrolled hypertension: A neglected risk in patients with NAFLD

Dear Editor, Non-alcoholic fatty liver disease (NAFLD) and hypertension share a bi-directional relationship, and both conditions are major risk factors for adverse cardiovascular events [1, 2]. Thus, patients suffering from both represent a population at substantial cardiovascular disease (CVD) risk. Even though hypertension affects up to 50% of all NAFLD patients, the diagnosis of hypertension, as well as the evaluation of treatment control among NAFLD patients, is often based exclusively on office (OBP) instead of out-of-office blood pressure measurements, e.g. 24-h ambulatory blood pressure monitoring (24-h-ABPM), as recommended by current guidelines [3-5]. To improve hypertension management among NAFLD patients, we integrated a 24-h-ABPM-based hypertension screening and control program into NAFLD outpatient care. Here we report our preliminary results on hypertension awareness, treatment and control in this distinctive population at high CVD risk. A total of 226 NAFLD patients were consecutively recruited during follow-up visits to our outpatient department between December 2019 and June 2021 (clinicaltrials.gov-identifier: NCT-04543721). The study protocol was approved by the Ethics Commission of Cologne University's Faculty of Medicine (approved research protocol no.: 20-1048), and written informed consent was obtained from each study participant. All study procedures were performed in accordance with the Declaration of Helsinki. Medical history, anthropometric data, OBP measurements and 24-h-ABPM were documented following a standardized protocol. Blood pressure status was defined according to the current ESH/ESC guidelines [3]. Uncontrolled hypertension was defined as elevated out-of-office blood pressure in treated or untreated individuals. See supplementary material for detailed information. Out of 226 originally recruited patients, eight participants had to be excluded because they stopped the 24-h-ABPM recording prematurely or had fewer than the required ABPM recordings. The median age of the included 218 patients was 51 years, and 48.2% were female. 87.2% of the study participants were overweight (BMI ≥ 25 kg/m2, n = 80) or obese (BMI ≥ 30 kg/m2, n = 110), and 24.3% (n = 53) suffered from type 2 diabetes. At the time of ABPM, 93 of 101 (92.1%) NAFLD patients with a prior history of hypertension received antihypertensive treatment. Among those on antihypertensive monotherapy (n = 41), eight were taking drugs with potential adverse metabolic effects, i.e., beta-blockers or thiazides (Table S1). Controlled hypertension (OBP and ABPM normotension) was confirmed in only 23 of these 93 (24.7%) patients with known and treated hypertension, while 47.3% (n = 44) of study participants on antihypertensive treatment revealed sustained uncontrolled hypertension (OBP and ABPM hypertension). Masked hypertension (normal OBP with elevated out-of-office BP) was identified in 42 (19.3%) NAFLD patients, 18 of whom were receiving antihypertensive treatment (masked uncontrolled hypertension). Nocturnal hypertension was observed in 109 (50%) NAFLD patients. Individuals with diabetes were significantly more likely to have isolated systolic hypertension than those with no diabetes (22.6% vs. 9.1%, Chi2 p = 0.021). A new diagnosis of hypertension, including masked and sustained hypertension, was established in a total of 65 (29.8%) study participants (see Fig. 1 and Table S1). The findings of the present study demonstrate that hypertension represents an uncontrolled burden among NAFLD patients. While more than half of the patients had normal BP values within the office, about 60% of the present cohort of NAFLD patients in fact suffered from uncontrolled hypertension according to 24-h-ABPM. This is markedly higher than the previously reported rates of about 40% from the general population [6]. Hypertension was newly diagnosed in approximately every third participant of the present cohort (29.1%), reflecting a concerningly high level of hypertension unawareness. Because individuals with untreated or uncontrolled hypertension are at increased risk of CVD-specific mortality, this will undoubtedly further enhance the CVD risk of NAFLD patients [7]. Thus, the present findings underscore the need for hypertension screening and management programs in NAFLD care. To use ABPM within such programs seems necessary, as it has been shown to be superior to OBP measurements in predicting total and CVD mortality together with its distinctive role in identifying high-risk BP phenotypes, such as masked hypertension [4, 8]. Masked hypertension confers a cardiovascular risk almost equivalent to that of sustained hypertension and could be confirmed in 19.3% of the study participants, who had normal office BP values. These findings highlight the fact that relying on OBP measurements alone will underestimate the true inherent burden of arterial hypertension among NAFLD patients. This study has several limitations, including the lack of a control group and the fact that only a single 24-h-ABPM recording was performed with its known limited reproducibility over time [9]. The absolute number of patients with distinctive hypertension phenotypes was overall low, and cardiovascular endpoints were not assessed. Furthermore, we studied a Caucasian population, and the results may not apply to people with different ethnic backgrounds [10]. In conclusion, given the high rates of uncontrolled hypertension among patients with NAFLD, the implementation of adequate hypertension screening and management programs including 24-h-ABPM into patient-centered care could substantially reduce the CVD burden in this distinctive cardio-metabolic risk group. PK and HMS designed the study; AM, AMZS, TG and JS provided assistance with data acquisition and study patient recruitment; SL and MD provided assistance for statistical analysis. PK, AM and HMS drafted the manuscript. All authors critically reviewed and approved the manuscript in its final form. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article. The data underlying this article will be shared on reasonable request made to the corresponding author. 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