General Considerations
Bengt Sjögren, ... Per Gustavsson, in Handbook on the Toxicology of Metals (Fourth Edition), 2015
1 Introduction
Cardiovascular disease (CVD) is the leading cause of death in the developed as well as in the developing world. The annual mortality of CVD is expected to reach 23.6 million by 2030 (Alissa and Ferns, 2011).
CVD is a group of diseases that includes coronary heart disease (CHD), cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, deep vein thrombosis, and pulmonary embolism (WHO, 2012). Sometimes the term circulatory diseases is used to encompass all of these diseases. CHD is a disease of the blood vessels supplying the heart muscle. This condition is often called ischemic heart disease (IHD) and acute myocardial infarction belongs to this entity. Cerebrovascular diseases are subdivided into ischemic and hemorrhagic diseases. Stroke is a widely used unspecific term for a group of cerebrovascular diseases of abrupt onset that cause neurological damage. Approximately 85% of strokes are caused by inadequate blood flow to the brain, i.e. ischemic stroke. Hemorrhagic strokes are subdivided into hemorrhage into the brain tissue and hemorrhage into the subarachnoid space (Zivin, 2004). The main representative of peripheral arterial disease is hypertension. Terminology used in the different studies was retained in the following text.
The most common cause of CVD is atherosclerosis. Atherosclerosis has an inflammatory nature, which was described by the Austrian pathologist Carl von Rokitansky in the 1840s and by Rudolf Virchow somewhat later. Rokitansky believed that inflammation was secondary to other disease processes and Virchow promoted atherosclerosis as a primary inflammatory disease (Frostegård, 2010; Mayerl et al., 2006). The response-to-injury hypothesis was summarized by Ross (1993). This theory postulates alteration to the endothelium and intima, due to for example mechanical injury, toxins, and oxygen radicals, as the initiating event leading to endothelial dysfunction. During the last two decades more data has linked inflammation to the occurrence of atherosclerosis and thrombosis (Epstein et al., 1999; Libby et al., 2002; Ridker, 1999; Ross, 1999). Several markers of inflammation such as interleukin-6 (IL-6), fibrinogen, C-reactive protein (CRP), serum amyloid A protein, and increased leukocyte cell count are established risk factors for IHD (Danesh et al., 1998, 2000, 2005, 2008).
Environmental studies focus on the general population, and the exposure route is almost always ingestion of metals or metal-containing compounds. Prospective studies are more conclusive because the exposure by definition occurs prior to the effect or disease outcome. Consequently, cross-sectional studies are regarded as less conclusive. Occupational studies focus on a specific occupational group or a specific metal exposure, and the exposure route is inhalation as a rule. In many studies of occupational exposures, the CVD mortality for one specific occupational group is compared with the national mortality. Such comparisons may be biased because the general population includes sick and disabled people who are unable to work.
This is a condensed review, mainly focusing on epidemiological studies of environmental as well as occupational exposures to metals and metal-containing compounds and their relations with CVD.