In a nationwide case-control study of prodigious proportions, endoscopically confirmed GERD in patients without known coronary or peripheral artery disease at baseline was independently associated with 57 percent increased risk of having a first acute MI within the next five years, reported at the annual Digestive Disease Week.
If this novel finding is confirmed in other databases, the clinical implication would be profound. GERD is after all an extremely common problem, affecting 30 percent-40 percent of the US population, noted at Metro Health Medical Center and Case Western Reserve University, Cleveland.
The good news: When divided the 316,390 study participants with GERD into those who were on proton pump inhibitor therapy and those who weren’t at increased MI risk, compared with the more than 13.6 million similarly aged control subjects who didn’t have GERD, had never undergone an upper endoscopy, and were free of known atherosclerotic disease at baseline. Effective treatment of GERD appears to protect against MI.
The study population was drawn from Explorys, a private, cloud-based health database containing the electronic health records of 35 million U.S. patients as provided by more than 200,000 physicians in 300 –plus health care systems.
A first MI occurred during follow-up 18,860 GERD patients, or 5.96 percent, compared with 144,140 controls, or 1.05 percent. This translates into an unadjusted sixfold increased risk of acute MI in patients with rigorously diagnosed GERD, compared with GERD –free controls.
The investigators then performed a multivariate logistic regression analysis adjusted for six major cardiovascular risk factors: obesity, hypertension, diabetes, tobacco use, hyperlipidemia and sex. Many of these risk factors were substantially more prevalent in the GERD population. As a result, the unadjusted sixfold increase in MI risk associated with GERD was attenuated in this adjusted risk model; however, the adjusted 57 percent increased risk remained highly significant.
Moreover, the increased relative risk of GERD seen in the multivariate analysis was comparable with the risks posed by many of the established risk factors. Obesity, for example, showed a 9 percent increase in MI risk, smoking a 90 percent increase, and hypertension a 10 percent increased relative risk, compared with normotension. Only hyperdelimia and diabetes were in another league, with relative risks of 9.5 –and 2.2 –fold, respectively.
They observed that during the past decade, the research focus has shifted away from GERD as a caustic disease process causing local injury to GERD as a systemic inflammatory disease. Among the proinflammatory cytokines shown to be elevated both in the esophagus and circulation of GERD patients are interleukins -6, -8, and -1B as well as platelet –activating factor. These cytokines are well established as important players in the formation of atherosclerotic plaque in arteries. It was the shared elevations in proinflammatory cytokines that led to hypothesize that patients with GERD might have an increased incidence of MI.
Diabetes, for example, has been repositioned from a straightforward endocrine disease to new status as a coronary heart disease equivalent. And strong bodies of evidence link psoriasis and periodontitis to increased cardiovascular risk.
Search suggested another possible mechanism for the apparent protective effect of PPIs against MI: Effective treatment of GERD; whether using PPIs or via a fundoplication procedure, has been reported to reduce levels of the inflammatory cytokines present in GERD.