- Mohammad Faisal
Association of moderate to severe Carbon Monoxide (CO) poisoning and Cardiovascular disease
Carbon monoxide (CO) is colorless and odorless gas which can be very fatal and has important clinical values mainly due to the toxicological affects it can create. A broad range of studies suggest that acute CO poisoning may cause sudden deaths and other deadly clinical manifestations such as toxicity of central nervous system, comma etc. In USA 50,000 cases of CO poisoning along with 2700 deaths are reported each year (Lee, F. et al., 2015). However, the relationship between moderate to severe CO poisoning and developing cardiovascular diseases (CVDs) has not been studied properly even though CVD is assumed to be a frequent outcome of CO poisoning (Henry, C. R. 2006). Since general people might easily be exposed to CO through incorrectly installed, poorly ventilated or poorly maintained household appliances, it is not uncommon to be exposed to various level of CO poisoning as well. Therefore, in this literature review I have explored the correlation between moderate to severe CO poisoning and cardiovascular risk in the general population ranging from children to adults. Usually carboxyhemoglobin (COHb) and hemoglobin (Hb) concentrations are measured in order to determine the extent of poisoning (moderate to severe) caused by CO. The articles regarding acute CO poisoning are not considered in this review since it usually causes sudden death and reports regarding acute CO poisoning and long term manifestation of CVD is not clear and very limited. In this review, in total 7 articles were used; five of the studies were published during the last 7 years, whereas 2 of them were published in 2006.
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Relationship of CO poisoning to Myocardial injury and Peripheral artery disease
Moderate to severe CO poisoning was studied in a prospective cohort study from 1994 to 2002 in Hennepin County Medical Center. The study was followed up till 2005 and the investigators found that myocardial injury (MI) was a frequent clinical manifestation in the moderate to severe CO exposed group. The two markers of MI: cardiac troponin I or creatine kinase-MB levels were measured and found to be higher among the exposed group than usual. Investigators determined that the hazard ratio (HR) of patients who eventually died from MI and who died from other consequences other than MI was 2.1 (95% CI: 1.2-3.7) (Henry, C. R. 2006). In another retrospective study in Taiwan, investigators examined a large cohort of patients who were subjected to CO poisoning and compared them with a frequency matched control cohort at a ratio of 1:4. The study was done from 1998 to 2010 and the investigators used Cox proportional hazards regression models for their analytical approach. Outcome was measured using angiography, magnetic resonance angiography and it was found that the patients exposed to moderate to severe CO poisoning had 1.85-fold higher chances of developing peripheral artery disease (PAD) compared to the control group. However the risk was much higher between the two groups when some comorbidities such as hyperlipidemia and diabetes were ignored, which eventually supported the CO poisoning and peripheral artery disease (PAD) more strongly (Chen, Y. et al., 2015).
Risk of Developing Cardiovascular disease
Since moderate to severe CO poisoning is related to myocardial injury, a large retrospective cohort, somewhat similar to the previous one mentioned above was done considering the CO poisoning and hospitalization data from 2000 to 2011. Investigators found a significant association between CO poisoning and arrhythmia among the CO poisoned patients (1.83 fold higher) compared to the control cohort. Also a significant correlation was seemed to exist with Coronary artery disease (CAD) and Coronary heart disease (CHD), but the correlation was not statistically significant after adjusting for confounders (Lee, F. et al., 2015). This study was particularly important considering the fact that most of the previous studies, regarding this association were done in small scale. For example, a case report between CO poisoning and subsequent development of cardiomyopathy was reported in a restaurant worker who was diagnosed with very high levels of cardiac enzymes along with high carboxyhemoglobin, even though he was ruled out of acute ischemic heart disease according to diagnosis reports (Kim, H et al., 2015). This type of study indicates an association of CO poisoning with cardiovascular disease but as mentioned before it wasn’t enough to be convincing and required large sample based investigation rather than any individual case report to establish the association. For this reason, the two cohorts, done from 1998 to 2010 and 2000 to 2011 were particularly important in this regard.
In Hennepin County Medical Center (HCMC), 230 patients who were diagnosed with moderate to severe CO poisoning were examined, and investigators reported frequent cardiovascular and myocardial injury (MI). Among those patients 35% had elevated levels of creatine kinase or troponin I (cardiovascular biomarkers) along with 37% MI injury biomarkers. Even most of the patients who died during hospitalization, were diagnosed with cardiac arrest, Coronary artery disease (CAD) along with abnormal electrocardiogram (ECG) (Satran, D et al., 2006). However, some case reports indicated a difficulty of diagnosis between severe CO poisoning and myocardial injury due to a large spectrum of confusing symptoms of CO poisoning. CO poisoning is often involved with tissue hypoxia which might indicate neurological manifestations other than cardiovascular manifestations and make the diagnosis procedure somewhat complex (Grieb, G. et al., 2011).Â Most of the reported studies regarding CO poisoning and cardiovascular manifestations were conducted with adult participants. However, a particular study indicated that CO poisoning may have more harmful effects to infants and children than the adults due the fact that, the basal metabolic rate along with the tissue oxygen demand is much higher in children. This study was conducted between 2004 to 2007 and reported an association between CO poisoning and cardiovascular manifestations, according to the diagnosis reports of elevated cardiovascular biomarkers among children under 17 years of age, but surprisingly the electrocardiogram (ECG) reports were normal (Teksam, O. et al., 2010).
There are some limitations in the studies regarding moderate to severe CO poisoning and cardiovascular manifestations. Even though, in some studies- an association to CVD was shown, information regarding participants’ use of medication, or any previous treatment for CVD was not available which might have been influential. Moreover, some of the the risk factors such as smoking, dietary pattern, obesity etc. were missing (Chen, Y. et al., 2015). Some studies were retrospective which may not establish a causal relationship between the exposure and outcome. Investigators also suspected miscoding and misclassification in some cases of disease definition. Some other factors such as family history of CVD, educational background, socioeconomic status were also missing. Another important limitation was lack of sufficient laboratory data including electrocardiogram (ECG), and other cardiovascular markers which were considered to be vital for CVD manifestation as well. In some study, investigators were uncertain whether the patients developed cardiovascular disease before they were exposed to CO poisoning. Patients who were diagnosed at later stages of any study were subjected to loss to follow-up for long term analysis of CVD morbidity (Lee, F. et al., 2015). Finally, the epidemiological and geographical differences may not be generalized to USA and other countries.
Moderate to severe carbon monoxide (CO) poisoning is responsible for tissue hypoxia, which may ultimately lead to myocardial injury. Other than hypoxia, CO poisoning may also cause free radical formation, lipid peroxidation, and nitric oxide (NO) induced cellular apoptosis-which all may be responsible for developing cardiovascular disease in long term. A prospective cohort study including the measurement of all these biomarkers for a reasonably long time would elucidate more clear association with CVD. It has been evident from some studies that diagnosis of CO poisoning is complex and risky to draw any conclusion for any association. So, other than depending on hospital based data, some other animal models like mouse can be used in this purpose at times.
Also, some studies showed some different clinical patterns of CO poisoning and CVD. In one study, a group of participants showed the presence of less cardiac risk factors even though they were subjected to severe CO poisoning. On the other hand, some other participants showed the presence of higher cardiac risk factors while they were subjected to moderate CO poisoning. Age and heart dysfunctions of some specific location e.g. left ventricular function were found to be coherent with the observed risk factors (Satran, D et al., 2006). In this regard these data need to be considered, even though many retrospective studies lacked these data. So, it can be said that future studies will definitely require the evaluation of serial biomarkers along with electrocardiogram (ECG) of all participants, who are exposed to moderate to severe CO poisoning. This will definitely help the therapeutic approach along with developing proper strategies to prevent any cardiovascular disease associated with moderate to severe CO poisoning.
Chen, Y., Lin, T., Dai, M., Lin, C., Hung, Y., Huang, W., & Kao, C. (2015, 10). Risk of Peripheral Artery Disease in Patients With Carbon Monoxide Poisoning. Medicine, 94(40). doi:10.1097/md.0000000000001608
Grieb, G., Simons, D., Piatkowski, A., Altiok, E., Eppstein, R. J., Bernhagen, J., & Pallua, N. (2011, 06). Carbon monoxide intoxication versus myocardial infarction: An easy diagnosis? Burns, 37(4). doi:10.1016/j.burns.2011.01.002
Henry, C. R. (2006, 01). Myocardial Injury and Long-term Mortality Following Moderate to Severe Carbon Monoxide Poisoning. Jama, 295(4), 398. doi:10.1001/jama.295.4.398
Kim, H., Chung, Y. K., Kwak, K. M., Ahn, S., Kim, Y., Ju, Y., Kim, E. (2015, 04). Carbon monoxide poisoning-induced cardiomyopathy from charcoal at a barbecue restaurant: A case report. Annals of Occupational and Environmental Medicine, 27(1). doi:10.1186/s40557-015-0063-2
Lee, F., Chen, W., Lin, C., & Kao, C. (2015, 03). Carbon Monoxide Poisoning and Subsequent Cardiovascular Disease Risk. Medicine, 94(10). doi:10.1097/md.0000000000000624
Satran, D., Henry, C., & Adkinson, C. (2006, 03). Cardiovascular Manifestations of Moderate to Severe Carbon Monoxide Poisoning. Annals of Emergency Medicine, 47(3), 298. doi:10.1016/j.annemergmed.2006.01.009
Teksam, O., Gumus, P., Bayrakci, B., Erdogan, I., & Kale, G. (2010, 08). Acute cardiac effects of carbon monoxide poisoning in children. European Journal of Emergency Medicine, 17(4), 192-196. doi:10.1097/mej.0b013e328320ad48
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