Epidemiology

Historically, dysfunction of the renal and urinary tract systems were the leading causes of mortality in persons with SCI. Improvements in the management of neurogenic bladder had led to a decrease in mortality from renal and urinary tract complications. Although the precise prevalence is not known, it is believed that CVD accounts for a significant proportion of morbidity and mortality in individuals with SCI. Ischemic and nonischemic heart disease is second only to pneumonia and respiratory system diseases as the underlying cause of mortality in individuals with SCI. DeVivo and Stover reported that ischemic and nonischemic heart disease accounts for 18.7% of all deaths of known cause in individuals with SCI. In fact, heart disease is the second most common underlying cause of death in persons with tetraplegia, and the leading underlying cause of death in persons with paraplegia or Frankel D level of injury. Combined, ischemic and nonischemic heart disease are the leading underlying causes of death in persons more than 5 years post injury. Whiteneck and colleagues reported that cardiovascular diseases were the most frequent causes of death among persons with SCI more than 30 years of age (46%) and more than 60 years of age (35%). This data is supported by a recent prospective study which suggested that diseases of the circulatory system were the most common (40%) underlying and contributing cause of death in individuals at least 1 year post injury.

Heart disease is the leading cause of death in the United States. The standardized mortality ratio (SMR) can be used to compare mortality rates for persons with SCI to that of the general population. DeVivo and Stover reported no increased risk of mortality due to ischemic heart disease in individuals with SCI (SMR = 1.2), but a significant increase in mortality due to nonischemic heart disease (SMR = 6.4). Garshick and colleagues demonstrated nonsignificant increases in SMR in disease of the heart (SMR = 0.59) or other diseases of the circulatory system (SMR = 1.49). However, both studies may be limited by availability of follow-up data or small numbers of deaths. A recent review of existing literature determined that there is no indication that individuals with SCI are at markedly greater risk for cardiovascular morbidity and mortality than able-bodied adults. Although the prevalence of CVD in individuals with SCI may not be increased, its place as the leading cause of death suggests that the prevention of CVD in persons with SCI is as critical to the maintenance of health as it is in the able-bodied population. However, diagnosis and treatment of CVD in individuals with SCI present challenges not encountered in the noninjured people.

These studies provide valuable insight into the causes of death in persons with SCI. Current focus lies on the identification and prevention of CHD. Unfortunately, both identification and prevention of CVD in individuals with SCI is challenging. The ability of a person with SCI, particularly a higher-level injury, to report an ischemic event may be limited because of interrupted sensory pathways. Noninvasive cardiac stress testing has revealed that 63% to 65% of subjects have evidence of silent myocardial ischemia after dipyridamole administration and thallium-201 myocardial perfusion single-photon emission computed tomography imaging. A cardiac event can pass unnoticed in some individuals.

Cardiovascular recommendations in the general population

The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) summarizes the current recommendations for management of elevated serum cholesterol levels in the general population. The recommendations are based on levels of serum low-density lipoprotein (LDL) cholesterol and are influenced by the coexistence of CHD and the number of cardiac risk factors. CHD risk factors include diabetes mellitus, symptomatic carotid artery disease, peripheral artery disease, abdominal aortic aneurysm, cigarette smoking, hypertension, low-serum high-density lipoprotein (HDL) cholesterol levels, family history of premature CHD, and age (≥45 years men, ≥55 years women). Risk estimates are established by determining a risk category for an individual, which serves as a basis for the treatment guidelines.

Cardiovascular recommendations in the general population

The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) summarizes the current recommendations for management of elevated serum cholesterol levels in the general population. The recommendations are based on levels of serum low-density lipoprotein (LDL) cholesterol and are influenced by the coexistence of CHD and the number of cardiac risk factors. CHD risk factors include diabetes mellitus, symptomatic carotid artery disease, peripheral artery disease, abdominal aortic aneurysm, cigarette smoking, hypertension, low-serum high-density lipoprotein (HDL) cholesterol levels, family history of premature CHD, and age (≥45 years men, ≥55 years women). Risk estimates are established by determining a risk category for an individual, which serves as a basis for the treatment guidelines.

Cardiovascular concerns in SCI

Contributing to the increased risk for CVD in persons with SCI is the fact that nearly all cardiovascular risk factors are increased in individuals with SCI. Their patterns of dyslipidemia place them at risk for the development of arteriosclerosis. Increased rates of diabetes, impaired glucose tolerance, metabolic syndrome, and obesity contribute to the development of CVD, all conditions that are worsened by physical inactivity. The ability to modify cardiac risk factors, such as increasing activity level, may be difficult or extremely limited. Additionally, a number of consequences of SCI impart additional potential risk to these individuals, such as blood pressure abnormalities and cardiac rhythm disturbances.

Lipid metabolism

Abnormalities in lipid profiles play a significant role in the development of CHD. Depressed HDL cholesterol and elevated LDL cholesterol are risk factors for CHD. Irregularities in lipid profiles are commonly seen in the setting of SCI. Although consensus has not been reached on the impact of SCI on lipid profiles, agreement has been achieved on specific points. It is generally accepted that HDL cholesterol levels are depressed in individuals with SCI. In one study, HDL cholesterol levels in persons with paraplegia or tetraplegia were lower compared with controls (37 ± 1 or 40 ± 1 versus 48 ± 2mg/dL). Thirty-seven percent of subjects with SCI had HDL cholesterol levels less than 35mg/dL, suggesting more stringent recommendations for target lipid levels. Forty percent of individuals with SCI and LDL cholesterol levels between 130 and 160mg/dL also had serum HDL cholesterol levels below 35mg/dL. In this subgroup, the HDL cholesterol level would have been undetected if lipoprotein profiles were only tested to record total cholesterol levels. Total serum cholesterol levels are often lower in persons with SCI, in part owing to depressed HDL cholesterol levels. Neurologic level of injury appears to impact cholesterol levels in SCI. Serum HDL cholesterol was lower in persons with tetraplegia versus paraplegia, and the group with tetraplegia had a higher proportion of subjects with serum HDL cholesterol levels less than 35mg/dL than those with paraplegia. A significant inverse relationship was found for the degree of neurologic deficit and mean serum HDL cholesterol levels; individuals with motor complete injury had lower levels of HDL than those with motor incomplete injuries within the subgroups of tetraplegia and paraplegia. This suggests that greater severity of neurologic injury correlates with increased abnormalities in lipid profiles.

Ethnicity and gender are believed to have an effect on lipid profiles in persons with SCI. In a study of 600 subjects with chronic SCI, the mean serum HDL cholesterol was found to be significantly higher in an African American group studied when compared with a white and Latino group. White and Latino males with SCI, but not females or African American males, were found to have lower HDL cholesterol levels than able bodied sedentary control subjects. Some studies suggest that mean serum LDL cholesterol levels are not significantly different in individuals with SCI when compared with controls, while others report that LDL cholesterol, total cholesterol, and triglyceride levels are lower in individuals with SCI compared with control groups. Increased activity level appears to have a favorable affect on lipid levels. De Groot and colleagues noted that serum HDL cholesterol levels were significantly related to all measured physical capacity measures, including peak oxygen uptake, peak power output, and sum of handheld dynamometry measurements. This suggests that improving physical capacity by increasing physical activity in individuals with SCI may improve lipid profile, thereby reducing the risk of CHD. At the present time, literature suggests increased activity levels, in addition to smoking cessation and pharmacologic treatment may reduce CVD risk, although studies to clearly support this in the SCI population are needed.

Smoking and SCI

Smoking is recognized as a risk factor for CHD in the general population. In addition to the well-accepted association of cigarette smoking with cancer and respiratory complications, smoking is believed to be associated with reduced HDL cholesterol, by mechanisms that are not clearly understood. This may compound the already reduced levels of HDL cholesterol noted in individuals with SCI. Additionally, individuals with SCI may experience deterioration in pulmonary status as the result of smoking to a greater degree than the general population. This is supported by alterations in pulmonary function testing in smokers with SCI, such as reduced forced expiratory volume in 1 second and peak expiratory flow rate, reduced ratio of forced expired volume in 1 second to forced vital capacity, and increased functional residual capacity and residual volume. Smoking may also be a risk factor for the development of pressure ulcers and is associated with a higher incidence and more extensive pressure sores in individuals with SCI. Further, smoking contributes to overall decreased self-reported health-related quality of life.

Diabetes mellitus and impaired glucose tolerance

Diabetes mellitus is an independent risk factor for CVD and reduction of CVD risk factors in persons with SCI and diabetes is critical. It is estimated that 13.4% to 22% of people with SCI have diabetes. In a study of 100 veterans with SCI and 50 able-bodied control subjects, 22% of veterans with SCI were diabetic compared with 6% of control subjects. Eighty two percent of able-bodied control subjects had normal glucose tolerance compared with 38% of individuals with tetraplegia and 50% of those with paraplegia. Elevated levels of serum glucose and insulin are noted in response to oral glucose tolerance testing. Bauman and Spungen reported that after an oral glucose load in subjects with chronic SCI, 13.4% met criteria for the diagnosis of diabetes mellitus and 28.8% had impaired glucose tolerance. Of note, in this study, the diagnosis of diabetes would not have been made in 19 of 27 subjects based on fasting serum glucose values, suggesting that fasting serum glucose levels are inadequate for diagnosing diabetes in this population. Because the average fasting plasma glucose is only mildly elevated or within average range in people with SCI, it is believed that insulin resistance is the major factor responsible for glucose intolerance. Data suggests that abnormalities in carbohydrate handling occurred at younger ages in those with SCI. Veterans 50 to 64 years of age have twice the likelihood of having diabetes as those 50 years or younger. Veterans over 65 years of age are three times as likely to have diabetes as those under 50 years of age. There is conflicting data relating to the neurologic level of injury and diabetes. In SCI veterans, it was found that those with paraplegia had a higher proportion of diabetes (17.2%) than those with tetraplegia (12.3%). However, Bauman and colleagues, found that more subjects with complete tetraplegia demonstrated a disorder of carbohydrate metabolism than other neurologic deficit subgroups. Ethnicity may play a role in the development of diabetes in individuals with SCI; Banerjea and colleagues reported that blacks were 53% and Hispanics 74% more likely to have diabetes than were whites. Gender may also play a role in the development of diabetes and impaired glucose tolerance; it was noted that plasma insulin levels were higher in males than females at intermediate time points following an oral glucose load, suggesting a relative state of insulin resistance. When diabetes occurs in persons with SCI, those with diabetes had twice the likelihood of macrovascular and microvascular complications than those without diabetes.

A higher body fat content was found to be strongly associated with higher peak serum glucose and plasma insulin levels. The loss of lean tissue mass has been demonstrated to occur in persons with SCI. Additionally, the muscle tissue that remains has been demonstrated to contain a fourfold higher intramuscular fat percentage than in able bodied subjects by magnetic resonance imaging. This loss of lean tissue mass may affect the way insulin is managed within the body and may further contribute to elevated glucose and insulin levels in individuals with SCI. The precise mechanism of insulin resistance is multifactorial and is in part due to denervated muscle, decreased lean muscle tissue, and increased fat tissue. There appears to be an association between glucose intolerance, insulin resistance, and SCI, related to inactivity and increased adiposity. These adverse changes in body composition may negatively impact carbohydrate and lipid metabolism, which then increases the risk for CVD. Further studies are needed to evaluate the relative contributions of these specific factors to glucose intolerance, insulin resistance, and the development of diabetes. Diabetic care for individuals with SCI can improve with the implementation of coordinated, comprehensive care and increased health care provider awareness of the risks of CVD and diabetes this population. Rajan and colleagues found that clinical outcomes, as measured in terms of glycosylated hemoglobin, blood pressure, and lipid values were improved in Veterans with SCI over a 3-year period for those receiving care at a Veterans Affairs Medical Center, either within the SCI system of care or primary care setting.