London—Could use of calcium-channel blockers, which are frequently prescribed for high blood pressure, increase the risk that patients will develop diverticulosis?
A new report in the journal Circulation suggests that might be the case.
Imperial College, London–led researchers used genetic analysis in early-stage research to reach that conclusion; the study team was investigating the effectiveness and side effects of three common blood pressure medications: angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and calcium-channel blockers (CCBs).
Researchers point out that the three medications are used by millions of patients, but gauging potential side effects can be difficult and involve lengthy and expensive clinical trials. As an alternative, the team employed genetic analyses to study the effects of the medications. To do that, the investigators identified the proteins targeted by the drugs, which combat hypertension. They then analyzed genetic data from about 750,000 patients to pinpoint genetic variants that code for these proteins, and finally, studied whether those gene variants—which cause increased production of these proteins—were linked to an increased or decreased risk of other diseases.
Much as the researchers expected, they found that the genetic variants that coded for the proteins involved in lowering blood pressure were linked to lower heart disease and stroke risk. However, they also determined, after assessing the risk of around 900 different diseases using data from the Unite Kingdom Biobank study, that the versions of genes related to the effects of a particular type of calcium-channel blocker—the nondihydropyridine class—were also linked to an increased risk of diverticulosis, which causes small bulges or pouches to appear in the lining of the intestine.
Study authors report that their phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio [OR], 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (OR, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio [HR] 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (HR, 1.04; 95% CI, 0.83-1.32).
Calling for larger trials, lead author Dipender Gill, MD, noted, “This is the first time that this class of blood pressure drug has been associated with diverticulosis. We’re not sure of the underlying mechanism—although it may relate to effects on the function of intestine muscles, which perform contractions to transport food through the gut.”
“Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications,” study authors conclude. “The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.”
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A new report in the journal Circulation suggests that might be the case.
Imperial College, London–led researchers used genetic analysis in early-stage research to reach that conclusion; the study team was investigating the effectiveness and side effects of three common blood pressure medications: angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and calcium-channel blockers (CCBs).
Researchers point out that the three medications are used by millions of patients, but gauging potential side effects can be difficult and involve lengthy and expensive clinical trials. As an alternative, the team employed genetic analyses to study the effects of the medications. To do that, the investigators identified the proteins targeted by the drugs, which combat hypertension. They then analyzed genetic data from about 750,000 patients to pinpoint genetic variants that code for these proteins, and finally, studied whether those gene variants—which cause increased production of these proteins—were linked to an increased or decreased risk of other diseases.
Much as the researchers expected, they found that the genetic variants that coded for the proteins involved in lowering blood pressure were linked to lower heart disease and stroke risk. However, they also determined, after assessing the risk of around 900 different diseases using data from the Unite Kingdom Biobank study, that the versions of genes related to the effects of a particular type of calcium-channel blocker—the nondihydropyridine class—were also linked to an increased risk of diverticulosis, which causes small bulges or pouches to appear in the lining of the intestine.
Study authors report that their phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio [OR], 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (OR, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio [HR] 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (HR, 1.04; 95% CI, 0.83-1.32).
Calling for larger trials, lead author Dipender Gill, MD, noted, “This is the first time that this class of blood pressure drug has been associated with diverticulosis. We’re not sure of the underlying mechanism—although it may relate to effects on the function of intestine muscles, which perform contractions to transport food through the gut.”
“Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications,” study authors conclude. “The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.”
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