Researchers Discover Gut-Heart Connection in Coronary Artery Disease

A newly discovered link between coronary artery disease and the overgrowth of bacteria in the small intestine presented by Cleveland Clinic researchers at Digestive Disease Week 2015 today means that there may soon come a day when the standard of care will be for gastroenterologists and cardiologists to exchange patients for additional evaluations.

After treating a patient’s primary illness, a gastroenterologist would send a patient with bloating or abdominal discomfort to a cardiologist to be checked for coronary artery disease (CAD). And, likewise, cardiologists would send patients with CAD for an additional evaluation with a gastroenterologist.

Although previous studies have shown a connection to the type of flora in the gut and inflammation in the coronary arteries, Cleveland Clinic researchers believe is the first study to look at the relationship between small intestine bacteria overgrowth, known as SIBO, and CAD.

And, that may directly impact treatment for some patients down the road.

“What our research adds is that patients with SIBO may be considered high risk for CAD and may need to have other CAD risk factors, such as hypertension, hyperlipidemia or diabetes, more aggressively controlled to decrease their chances of worsening coronary artery disease, leading to serious event like a heart attack,” says Cleveland Clinic gastroenterologist Bo Shen, MD, who specializes in inflammatory bowel disease.

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death in the United States for both men and women – with about 11.3 percent of the population suffering from CAD. The estimated rate of SIBO ranges up to about 20 percent in the healthy population, but skyrockets in patients with gastrointestinal disorders. For example, patients with irritable bowel syndrome (IBS) have about a 78 percent rate of SIBO.

Study Design

Multiple researchers have gained interest in the intestinal microbiome as a modulator of inflammation throughout the body. But there has not been any previous research evaluating the association of SIBO and CAD, says Dr. Shen.

Cleveland Clinic researchers believed that cause of the link may be due to the metabolic process in digestion that produces bacterial byproducts, predisposing a patient to CAD. For example, the metabolism of dietary choline produces trimethylamine, (TMA) which converts to trimethylamine-N-oxide (TMAO) in the liver. TMAO may cause artherosclerosis, leading to CAD.

To study this, researchers tested 923 patients between 2006 and 2014. Of those, they included 148 who underwent both a left heart catheterization and glucose hydrogen/methane breath test – the standard for detecting SIBO.

The rates of metabolic syndrome were also evaluated in the patients studied. Metabolic syndrome was defined as at least three of five criteria for metabolic syndrome: obesity/BMI > 30; triglycerides > 150 mg/dL; HDL cholesterol < 40 mg/dL (men) or 50 mg/dL (women); blood pressure > 130/85 mmHg; and fasting glucose > 110 mg/dL.

Researchers then compared the 81 (54.7%) of SIBO-positive patients with 67 (45.3%) SIBO-negative, or control group patients.

Patients with SIBO had an overwhelmingly higher frequency of arteries affected by CAD: 80.2 percent vs. 38.8 percent. In addition, SIBO-positive patients had more coronary arteries affected than non-SIBO patients: one-vessel disease, 67.2 percent.vs. 32.8 percent; two-vessel disease, 83.3 percent vs. 16.7 percent; and three-vessel disease, 80 percent vs. 20 percent.

A Bidirectional Relationship Between the Gut and the Heart?

What the study did not clearly distinguish is whether SIBO causes CAD or CAD causes SIBO.

“We actually don’t know the order of the causal relationship, and that’s what makes the research even more interesting,” explains Dr. Shen. “We postulate that there is a poorly understood gut-heart axis in which there is a bidirectional relationship: SIBO, through the increased production of bacterial byproducts, may predispose a patient to CAD. On the other hand, CAD and atherosclerosis may be related to proinflammatory cytokines that lead to changes in the gut microbiota equilibrium.”

Through a multivariable logistic regression analysis, SIBO remained the independent risk factor in the group that linked with CAD. However, other research has shown a possible relationship between the intestinal microbiome and obesity, and many of the patients in the study were obese. But, what, if any, is the connection?

“It is thought that gut bacteria may induce obesity,” Dr. Shen says. “SIBO has been shown to be more common in morbidly obese patients, and we don’t know if it is a cause or a consequence.”

Future Research

In addition to obesity, SIBO has been linked to diabetes and nonalcoholic fatty liver disease. Dr. Shen says further research is needed to understand the role SIBO plays in these metabolic disorders.

But the first step, Dr. Shen says, is to confirm that SIBO is a risk factor for CAD, or vice-versa.

“In addition, it is important to elucidate if treating SIBO improves cardiovascular outcomes in these patients,” says Dr. Shen.

If that proves true, research will need to find the best treatment. Antibiotics are the current standard treatment for SIBO. However, antibiotics can kill off even “good” intestinal flora, so Dr. Shen says there may be a need for probiotics to stabilize gut flora and decrease inflammation, or prebiotics that can encourage the growth of certain bacteria.

While further research is needed, the connection between the gut and the heart and the body’s inflammatory process could lead to new treatment protocols for patients, says Dr. Shen.

For more information, contact Dr. Shen at shenb@ccf.org.