To study this question, University of Chicago epidemiologist Habibul Ahsan returned to his project studying the consequences of accidental arsenic exposure in the people of Bangladesh. Ahsan’s Health Effects of Arsenic Longitudinal Study (HEALS) has tracked thousands of Bangladeshi citizens who unknowingly consumed well water with high levels of arsenic after health organizations installed wells to reduce water-borne infectious disease. That study, which has expanded to 20,000 subjects, discovered a 70 percent higher risk of death from chronic disease in those drinking water with the highest levels of arsenic. Even people exposed to moderate levels of arsenic, amounts that can be found naturally in some regions of the United States, were at a 20 to 30 percent higher risk of dying from chronic disease.
Ahsan and his team from UChicago, Columbia University, New York University, and Bangladesh, looked at whether the combination of arsenic exposure and smoking made the odds even scarier on one particular mortality endpoint: cardiovascular disease. While arsenic is traditionally thought of as causing different types of cancer and skin lesions, chronic exposure can also produce various heart and circulatory problems such as hypertension and atherosclerosis. Previous studies of these cardiovascular effects have been small, retrospective, and focused on extremely high exposures in Taiwan and Chile. With the Bangladesh study, Ahsan and colleagues could look at a broader spectrum of exposure, and follow subjects carefully over time to isolate the effect of arsenic from other factors.
For the study, published last week in the British Medical Journal, the researchers tracked nearly 12,000 Bangladeshis, taking urine samples to measure arsenic exposure and registering the cause of death in those who died over the time they were tracked (an average of 6.6 years). Overall, 460 subjects died, with nearly half of those (198 people) dying from some form of cardiovascular disease. Associating those deaths with arsenic exposure confirmed the Taiwan and Chile studies on people exposed to high concentrations (as high as 80 times the safe limit of 10 parts per million) of the toxin. But a worrisome trend also emerged for more moderate exposures, with a 50 percent increase in cardiovascular mortality risk observed at levels as low as 2.5 times the safe limit.
“We were able to show that, even at lower doses than previously reported, there seems to be a deleterious effect of arsenic regarding cardiovascular disease mortality, particularly from ischemic and other heart diseases,” Ahsan said.
For those subjects who were smokers – even those who had quit – a deadly synergy emerged. For a current smoker exposed to the high levels of arsenic, the increased risk of dying from cardiovascular disease jumped from 50 percent to 328 percent. Former smokers saw a lower bump in risk, but if exposed to moderate levels of arsenic, they shared the same risk as those exposed to high levels that had never smoked. Ahsan said that the result emphasized the importance of targeting multiple risk factors in improving public health around the world.
“This tells us that there are some individuals who are dying from cardiovascular disease solely because of the presence of both factors, not because of the presence of one or the other,” Ahsan said. “It’s one more reason to pay attention to arsenic exposure, but yet another reason that will underscore the importance of smoking cessation.”
Beneath the epidemiology, a biological mystery about the interaction of smoking and arsenic exposure lingered. Curiously, the effect of arsenic on cardiovascular mortality appeared to be limited to ischemic and heart disease, rather than cerebrovascular diseases such as stroke. So while the toxin is known to narrow arteries, this atherosclerosis is somehow limited to vessels of the body and not the brain. Ahsan’s laboratory is now pursuing experiments to look at biomarkers such as arterial wall thickness to see if there is an effect upon known pre-clinical markers of heart disease. Early identification of arsenic-related heart disease could help doctors try to intervene to offset the toxin’s effects, thanks to a small double-edged feature of the link with cardiovascular disease.
“The latency, the period of exposure to arsenic that is needed for diseases to manifest, seems to be lower for cardiovascular disease than cancers,” Ahsan said. “But at the same time, the benefit of arsenic exposure cessation also seems to take hold faster – you get the benefit of cessation on cardiovascular disease sooner than the benefits on preventing cancer.”
Chen, Y., Graziano, J., Parvez, F., Liu, M., Slavkovich, V., Kalra, T., Argos, M., Islam, T., Ahmed, A., Rakibuz-Zaman, M., Hasan, R., Sarwar, G., Levy, D., van Geen, A., & Ahsan, H. (2011). Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study BMJ, 342 (may05 2) DOI: 10.1136/bmj.d2431