Individuals with a history of Plasmodium falciparum protozoan parasitic infection had a significantly increased long-term risk of developing heart failure but not myocardial infarction or cardiovascular or all-cause death.
The study found that a history of Plasmodium falciparum infection, a known cause of malaria in humans, was associated with an increased risk of incident HF. There was no observed effect for Plasmodium vivax and Plasmodium ovale. Persons with a history of malaria had a significantly increased long-term risk of developing HF but not myocardial infarction (MI), cardiovascular death, or all-cause death.
This the first study to evaluate the long-term risk of cardiovascular events and death in individuals with a history of malaria. Although there has been progress in reducing the burden of the disease, malaria continues to be a leading cause of morbidity and mortality globally, with an estimated 220 million cases and 405,000 deaths reported each year.
“A potential link between malaria and increased risk of HF is of global scientific interest and may aid in understanding the increasing burden of cardiovascular disease in low- and middle-income countries,” the authors said. “Most medical strategies focus on eliminating the malaria parasite in affected individuals; yet none have assessed the long-term effects of malaria exposure.”
The cohort study used nationwide Danish registries to follow 3912 individuals with a history of malaria for risk of incident HF, MI, cardiovascular death, and all-cause death. Data were collected from January 1, 1994, to January 1, 2017, and those with malaria were matched with individuals without a history of malaria based on age and sex. Patients with known HF and ischemic heart disease were excluded.
Among the 3912 individuals with malaria, the mean (SD) age was 33 (17) years, 57% were male, and 41% had P falciparum infection. The median (interquartile range) follow-up was 9.8 (3.9-16.4) years.
Event rates per 1000 person-years for individuals with a history vs no history of malaria, respectively, for each condition were as follows:
When adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income, and educational level, malaria was associated with a 59% greater risk of HF (HR, 1.59; 95% CI, 1.21-2.09; P = .001). However, it was not associated with MI (HR, 1.00; 95% CI, 0.72-1.39; P = 1.00), cardiovascular death (HR, 1.00; 95% CI, 0.74-1.35; P = .98), or all-cause death (HR, 1.11; 95% CI, 0.94-1.30; P = .21). P falciparum infection, in particular, was associated with a 64% greater risk of HF (HR, 1.64; 95% CI, 1.14-2.36; P = .008).
“These findings support the hypothesis that malaria can cause subclinical myocardial damage, leading to decreased cardiac function and eventually HF,” the authors wrote. “Importantly, a majority of the clinical studies only included P falciparum malaria patients, which is the most serious form of malaria, not least due to the capacity of P falciparum–infected erythrocytes to adhere to vascular endothelium.”
According to the authors, it is mandatory in the Danish health care system to report all malaria diagnoses to the National Malaria Reference Laboratory. They did not have information on use of hydroxychloroquine, an antimalarial drug that may cause cardiomyopathy. They also lacked information on symptoms and paraclinical tests related to the severity of malaria. Because of this, the authors noted these results are “exploratory and hypothesis-generating in nature.”
“The present results bring novel attention to a potentially overlooked complication to malaria and warrant future prospective and larger studies to confirm the results,” the authors concluded. “If present, a causal relationship between malaria and cardiovascular disease would have global impact and could potentially lead to a paradigm shift on how to treat and control cardiovascular disease in malaria risk regions.”
Brainin P, Mohr GH, Modin D, et al. Heart failure associated with imported malaria: a nationwide Danish cohort study. ESC Heart Fail. Published online July 27, 2021. doi:10.1002/ehf2.13441