Improved control of hypertension following laparoscopic fundoplication for gastroesophageal reflux disease

Abstract

This study aims to determine whether successful laparoscopic fundoplication for gastroesophageal reflux disease (GERD) can improve the control of hypertension. We conducted an observational study of GERD patients with hypertension. The esophageal and gastroesophageal symptoms of these patients were successfully treated with laparoscopic fundoplication, as measured by the reduced GERD symptoms and proton pump inhibitor consumption. A hypertension control scale was used to classify the use of antihypertensive medications and the quality of blood pressure control before and after anti-reflux surgery. Wilcoxon signed-ranks test was used for the statistical analyses. Seventy GERD patients were included in the analysis and followed up for a mean period of 3.5±1.4 years. Prior to surgery, all participating patients were taking at least one class of antihypertensive medication, and 56 patients (80%) had intermittently high blood pressure. After surgery, the mean number of antihypertensive medication classes per patient was significantly reduced from 1.61±0.77 pre-procedure to 1.27±0.88 post-procedure (P < 0.001). The blood pressure of 48 of the 56 cases (86%) with preoperative intermittent high blood pressure returned to normal post procedure. A total of 50 patients (71%) recorded improvements on the hypertension control scale, with the overall mean score decreasing from 3.1±1.0 pre-procedure to 1.4±1.0 post-procedure (P < 0.001). Therefore, successful laparoscopic fundoplication may result in better blood pressure control in some hypertensive GERD patients. This result suggests a possible connection between gastroesophageal reflux and hypertension.

Keywords

gastroesophageal reflux disease / hypertension / blood pressure / laparoscopic fundoplication

Introduction

Gastroesophageal reflux disease (GERD) is a collection of symptoms, end-organ effects, and complications caused by the reflux of gastric contents into the esophagus, oral cavity, and/or the lungs [ 1]. The prevalence of GERD, which is typically estimated from reports of the characteristic heartburn and regurgitation symptoms, is estimated to be approximately 10%–20% in Western countries. The prevalence is lower in Asia, but appears to be increasing [ 2].

The spectrum of clinical presentations attributable to GERD has expanded from esophageal symptoms to a broader collection of gastroesophageal symptoms, including chronic cough and asthma [ 3]. However, the diverse array of health issues or comorbidities potentially associated with GERD remain largely under-recognized [ 3]. The potentially serious gastroesophageal complications or comorbidities that have been previously associated with GERD include various pulmonary, laryngeal, cardiovascular, and gastrointestinal diseases [ 4].

Essential hypertension is a cardiovascular disorder commonly observed in general practice [ 5]. Barrett’s esophagus and reflux esophagitis have been associated with an increased prevalence of hypertension and hypercholesterolemia relative to the general population [ 6]. Laparoscopic fundoplication (LF) is a commonly used surgical procedure for resolving the persistent heartburn and regurgitation symptoms in GERD, especially those in patients refractory to the proton pump inhibitor (PPI) therapy [ 7, 8]. Surgery can also decrease the reliance on medications for symptom control of up to 80%–90% of patients with gastroesophageal and extra-esophageal refluxes [ 9– 11]. An association between GERD and hypertension has been postulated, but the underlying pathophysiology of such a relationship is unknown. The hypothesis of this study is that successful GERD surgery may also improve blood pressure control in patients who demonstrated hypertension prior to surgery.

Material and methods

We performed a retrospective analysis of our GERD database of 1052 patients who underwent LF between January 2010 and January 2015. All patients included satisfied the guidelines of the 2010 Society of American Gastrointestinal and Endoscopic Surgeons Guidelines Committee for GERD surgery [ 11]. The surgical technique employed for all eligible patients was either laparoscopic Nissen or Toupet fundoplication, as described in our previous studies (Fig.1) [ 12, 13]. This study was approved by the Ethics Committee of the PLA Rocket Force General Hospital.

Inclusion criteria

The patients enrolled in this study were required to satisfy the following minimum inclusion criteria: (1) aged 18 years or older; (2) had documented pre-surgical hypertension; (3) underwent LF with at least 12 months of post-procedure follow-up; (4) had preoperative ambulatory 24-h esophageal pH monitoring and endoscopic and esophageal high-resolution manometry examination; and (5) recorded a successful post-surgical GERD outcome during the follow-up.

Definitions and instruments

Blood pressure and hypertension data were obtained from patient self-reports and medical records of the chronic use of antihypertensive medication and repeated systolic blood pressure readings of≥140 mmHg and/or diastolic readings of≥90 mmHg [ 5]. A successful LF for GERD was characterized by a minimum reduction of 50% in the GERD symptom score and PPI consumption, as measured by the Reflux Diagnostic Questionnaire. The Reflux Diagnostic Questionnaire (with revision) [ 14, 15] was used in this study to quantify patient symptoms and anti-reflux medication use at the time of admission until the follow-up. The instrument used a six-point scale ranging from 0 to 5 to assess both the severity and frequency of the GERD symptoms (five items, total score of 0–50). The three esophageal symptoms included regurgitation, heartburn, and chest pain, and the extra-esophageal symptoms were coughing and wheezing. The symptom score reduction rate was calculated as (preoperative symptom score – postoperative symptom score) / preoperative symptom score × 100%.

The use of PPI and anti-hypertensive medication, duration of hypertension, quality of blood pressure control, and body mass index (BMI) were assessed and collected at the time of admission and during follow-up. All subjects were monitored postoperatively until the end of the observation period in February 2016. Medication adjustments in the postoperative period were made at the discretion of each patient’s primary care physician. No established study protocol was used in the reduction or discontinuation of antihypertensive medications. The improvement of hypertension control was defined as (1) a reduction in the classes of antihypertensive mediations without dose increase and/or a reduction in the dose of antihypertensive medications or (2) reductions in the systolic blood pressure to under 140 mmHg and the diastolic blood pressure to under 90 mmHg. A hypertension control scale was used to objectively quantify the pre- and post-operative hypertension severities. A score of 0 was defined as the normal blood pressure without medication, 1 as the normal blood pressure with a single medication, 2 as the normal blood pressure with multiple medications, 3 as the intermittent hypertension with single medication, and 4 as the intermittent hypertension with multiple medications.

Statistical analyses

The GERD symptom scores, number of antihypertensive medications classes, and hypertension control scale scores before and after LF were compared using the Wilcoxon signed-ranks test. All values with P<0.05 were considered statistically significant. All analyses were performed using the SPSS version 13 software (IBM, Armonk, NY, USA).

Results

A total of 70 cases satisfying the inclusion criteria were included in the analysis and followed up for a mean period of 3.5±1.4 years after LF. The baseline characteristics of these patients at the time of surgery are described in Table 1. The mean age of the patients at the baseline was 48.7±11.5 years, and 37 patients (52.8%) were male. The mean duration of hypertension and GERD symptoms were 11.3±8.1 and 10.4±9.1 years, respectively. The mean BMI was 21.7±3.6. Nissen fundoplication was performed in 26 (37.1%) patients and Toupet fundoplication was conducted in the remaining 44 (62.9%). After LF, the combined GERD symptom scores across all five esophageal and extra-esophageal domains significantly decreased from a mean of 24.1±9.7 pre-procedure to 3.1±3.4 post-procedure (P<0.001, Table 2). This change corresponded with a combined GERD symptom score reduction rate of 86.9% (54.1%–100%). PPI therapy was discontinued in 51 patients (72.9%), and the remaining 19 patients recorded a minimum reduction of PPI use by least 50%.

The mean number of antihypertensive classes used per patient after surgery significantly decreased from 1.61±0.77 at the baseline to 1.27±0.88 (P<0.001) post-operatively. This trend included 13 patients (18.6%) who ceased antihypertensive medication, 9 (12.9%) who reduced their number of concurrent antihypertensive medications, and 7 (10.0%) who reduced their dosage. The remaining 41 (58.6%) patients had no postoperative changes in terms of their medication. In the 56 patients with intermittent high blood pressure prior to surgery on single or multiple antihypertensive treatments, the blood pressure of 48 patients (85.7%) stabilized to within a normal range after surgery. The observed reduction of the number of antihypertensive medications used and the postoperative normalization of blood pressure translated into an overall improvement in the hypertension control scale for 50 (71.4%) patients. Across all patients, a significant reduction in the mean hypertension control scale score from 3.1±1.0 pre-operatively to 1.4±1.0 post-operatively (P<0.001) was noted. A total of 13 cases were post-operatively classified as normal blood pressure without medication on the hypertension control scale (Table 3).

Discussion

In this study, we observed a significant improvement in the hypertension control scale after anti-reflux surgery across a mean follow-up period of 3.5 years. The mean number of antihypertensive medication classes significantly decreased post-operatively and the blood pressure stabilized within an acceptable range in most cases that demonstrated intermittent hypertension prior to surgery. Overall, 13 cases (18.6%) reported blood pressures in the normal range postoperatively, even after ceasing all antihypertensive medications. This trend suggests that hypertension in some patients may be secondary to GERD.

Obesity is a well-documented risk factor for hypertension [ 5]. Bariatric surgery management for obesity, including the Roux-en-Y gastric bypass, has been previously reported to result in the long-standing remission of hypertension in up to 93% of patients [ 16]. One potential mechanism underlying this phenomenon may involve obesity-associated hypertension, which increases the levels of adipocyte hypertrophy and macrophage infiltration. In turn, this phenomenon may alter the adipokine secretion from the adipose tissue [ 17, 18]. However, only a limited number of studies have investigated the potential association between GERD and hypertension. Any direct relationship between anti-reflux surgery and hypertension remains unclear.

PPI therapy is used in the management of GERD; this approach may be beneficial for patients with cardiovascular disease if they experience chest pain of cardiac and esophageal origins [ 19, 20]. Anginal pain with electrocardiographic evidence of cardiac ischemia could be provoked by acid perfusion [ 21]. The exertional angina threshold could be lowered by acid perfusion [ 22], thereby demonstrating the possible clinical relevance of acid-induced cardiac ischemia. The studies involving coronary artery disease patients monitored with ambulatory pH and electrocardiography demonstrated that the association of some episodes of cardiac ischemia with spontaneous acid reflux [ 23, 24] may further clarify the association of GERD and the cardiovascular system.

Another potential link between GERD and hypertension may involve an irritant gastroesophageal stimuli that alter the autonomic modulation of heart rate, which could lead to a cardiac dysrhythmia. A recent study reported a significant correlation between the episodes of acid reflux and dysrhythmia, thereby suggesting that idiopathic dysrhythmias could be triggered by esophageal acid stimulation [ 25]. We also previously documented a case of long-standing arrhythmia that improved the post-Stretta procedure for GERD [ 26].

Clear evidence supports the benefits of LF on typical esophageal and extra-esophageal GERD symptoms [ 7– 10]. The LF procedure confers these benefits via a complex array of mechanisms, including reduced esophageal and extra-esophageal reflux exposures [ 27, 28], decreased esophageal airways [ 29], esophago-cardiovascular reflexes [ 30, 31], and a possible reduction in the plasma levels of circulating hypertension mediators. A previous study observed a significant increase in nitric oxide metabolite plasma concentrations after eight weeks of gastric acid secretion suppression [ 32]. This trend may lead to the improvement of the overall blood pressure control, but more precise evidence is required.

Conclusions

A successful LF for the management of GERD symptoms may also cause better blood pressure control in some hypertensive patients. Our results indicated the potential association between GERD and hypertension. However, prospective studies are required to characterize this potential association better.

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