Effects of helminths and anthelmintic treatment on cardiometabolic diseases and risk factors: A systematic review

Abstract

Background Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and cardiometabolic diseases nor the effect of helminth eradication on cardiometabolic risk have been reviewed systematically in a large number of human and animal studies. Methods We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development and/or severity of cardiometabolic diseases and risk factors. The search was limited to the most prevalent human helminths worldwide. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and rerun on March 2, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently. Results Eighty-four animal and human studies were included in the final analysis. Most studies reported on lipids (45), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), atherosclerotic cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and non-atherosclerotic cardiovascular disease (4). Fifteen different helminth infections were represented. On average, helminth-infected participants had less dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. Eleven studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment increases in dyslipidemia, metabolic syndrome, and diabetes or glucose levels. Results from animal and human studies were generally consistent. No consistent effects of helminth infections on blood pressure, hsCRP, or cardiac function were reported except some trends towards association of schistosome infection with lower blood pressure. The vast majority of evidence linking helminth infections to lower cardiometabolic diseases was reported in those with schistosome infections. Conclusions Helminth infections may offer protection against dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. This protection may lessen after anthelmintic treatment. Our findings highlight the need for mechanistic trials to determine the pathways linking helminth infections with cardiometabolic diseases. Such studies could have implications for helminth eradication campaigns and could generate new strategies to address the global challenge of cardiometabolic diseases. Author summary Helminth infections are caused by parasitic worms and affect over 1.5 billion people worldwide. Helminth infections and cardiometabolic diseases are both common and overlap with one another in many parts of the world. Studies have separately examined the relationship between helminth infections and various cardiometabolic diseases, but the relationships overall, as well as the impact of treatment of parasitic worms, have not been studied systematically. The authors conducted a systematic review to assess the impact of helminth infections, and treatment of helminth infections, on cardiometabolic diseases and risk factors. Eighty-four total studies were analyzed and included in the final review. People and animals infected with helminths were generally found to have fewer cardiometabolic disease risk factors including better overall cholesterol profiles, less diabetes, and less atherosclerotic heart disease than uninfected study participants. After treatment of helminth infections, participants frequently experienced worsening in those cardiometabolic measurements. There were no consistent effects of helminth infections on blood pressure, high-sensitivity CRP (an inflammatory marker), or other cardiac function. In summary, helminth infections may offer protection against certain cardiometabolic diseases and risk factors. More studies are needed to elucidate the pathways linking helminth infections with cardiometabolic diseases as it may impact how we treat both disease processes in regions where both are prevalent.