Coronary Artery Calcification Score and Risk Factors for Coronary Artery Disease in Persons With Spinal Cord Injury

Overview

Although conventional risk factors for coronary heart disease (CHD) have been identified and routinely used to determine risk for CHD in the general population, a systematic approach to determine population-specific risk for CHD has not been performed prospectively in those with SCI. CHD is a leading cause of death in spinal cord injury, occurring at younger ages than in the able-bodied population. Conventional risk factors for CHD are high serum concentrations of low-density lipoprotein (LDL), low serum concentrations of high-density lipoprotein (HDL), diabetes mellitus (DM), positive smoking history, and positive family history of premature CHD. Coronary Artery calcification (CAC) is a commonly occurring phenomenon that does not necessarily indicate significant obstructive disease. Studies have shown that a strong association exists between coronary calcification and coronary heart disease. The purpose of this study is to compare the CAC scores in persons with SCI with a historical control group of able-bodied persons from a national data base who will be matched for conventional risk factors for coronary artery disease (CAD) and to determine the relationship between CAC scores and conventional and emerging risk factors for CAD. Additionally, postprandial lipemic (elevated levels of lipids following ingestion of food) responses among individuals with SCI and control subjects will be compared, as well as the response of inflammatory markers following a high fat meal. Participants will only be tested once for these parameters.

The early identification of individuals at high risk for development of CVD has been a challenging and highly relevant pursuit for clinicians and epidemiologists. The clinical significance of early identification of CAD becomes apparent because several of the cardiac risk factors are modifiable. Numerous studies have been performed to identify risk factors for CVD. These studies resulted in clinical guidelines for identification and risk reduction for CVD, currently summarized in the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel (ATP III). ATP III identifies five major risk factors for CVD: hyperlipidemia, hypertension, current smoking, abdominal obesity, and diabetes; individuals with two or more risk factors are considered at increased risk, although this recommendation may be changed to one risk factor in the upcoming ATP IV. From a clinical perspective however, shortcomings in the prognostic value of the current conventional risk factors are becoming increasingly apparent. Retrospective reviews of large cohort studies and clinical trials conducted in the general population have found that ≥1 major conventional risk factor was present in 90% of patients who had diagnosed CAD. However, approximately 70% of subjects with established risk did not develop an event related to CAD during a 21-30 year follow-up period. These findings suggest that major predictors of CAD risk, although up to 90% sensitive, may be just 30% specific. In persons with chronic SCI (\> 1 year), cardiovascular disease (CVD) is a leading cause of mortality, as it is in the general population. Compared to the general population, CVD-related morbidity in persons with SCI, specifically CAD, occurs earlier in life and is more prevalent. Based on this knowledge, the need for appropriate risk stratification in SCI population becomes apparent. Existing tools do not take into account specific consequences of SCI, possibly underestimating the actual risk for CVD. For example, most of the risk factor algorithms incorporate HDL cholesterol into their equations to determine CAD risk, with a cutoff level of HDL cholesterol below which the general population is at a heightened risk for disease. Such an approach does not factor in the severity of depression of HDL cholesterol. It is appreciated that the morbidity risk ratio for CAD in men rises above unity at an HDL cholesterol \<40 mg/dL, and the risk continues to rise in a linear fashion as the values for the lipid moiety decrease. In individuals with SCI, HDL cholesterol levels may be markedly depressed, with higher, more complete lesions having the lowest values. Thus, individuals with SCI will have additional risk for CAD based on extremely depressed values of HDL cholesterol that are not captured by conventional categorization. In addition, higher cord lesions (above thoracic level six) are frequently hypotensive, activating the renin-angiotensin axis in an attempt to maintain normotension. Elevated levels of angiotension are appreciated be atherogenic. Once again, this pathophysiologic condition-that is, hypotension and elevated angiotensin levels- is not captured by conventional risk factor paradigms. Because of these considerations, as well as the extreme immobilization of SCI that may independently confer additional CAD risk, the use of conventional risk assessment tools in this population is fraught with obvious difficulty and potential error. For years, the need for development of new non-conventional assessment tools has been recognized in the able-bodied population, and the need for a more reliable vehicle to identify individuals at heightened risk is even more the case in individuals with SCI. The predictive value of emerging risk factors has been studied in an attempt to increase both the sensitivity and specificity of the identification of individuals at heightened risk of CAD, and thus to improve early diagnoses and result in the appropriate institution of efficacious risk modification approaches. Abdominal fat, inflammatory biomarkers, CAC, arterial stiffness, increased C-reactive protein (CRP), vitamins and antioxidant deficiency, endothelial dysfunction, increased arterial intima media thickness (IMT), triglyceride response to fat load, and genetic factors have been extensively studied as potential predictors of increased risk for CAD in the general population. Among the non-conventional approaches, measurement of CAC scores has been most promising. CAC is highly specific to the atherosclerosis and is thought to develop late in its pathophysiology, reflecting a chronic plaque burden. CAC has been used in the global CVD risk stratification of asymptomatic patients to identify additional risk among those with a seemingly low-risk; the additional predictive value of CAC for CAD risk was greater than that provided by the conventional risk factors, regardless of racial or ethnic considerations. The higher the CAC score, the greater the prevalence of myocardial perfusion abnormalities associated with obstructive CAD and risk of death or myocardial infarction within 3 to 5 years. Approximately two-thirds of persons with SCI have intermediate risk for CAD; evidence suggests that many have silent CAD. Of note, and somewhat troubling, in reports in symptomatic individuals without CAC, 16-24% have obstructive CAD, an observation corroborated by the finding that approximately 20% of occluded vessels may not have detectable calcification.