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

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.

Inclusion Criteria:

- Males 45-75 years old with at least 5 yrs of SCI

- Females 50-75 years old with at least 5 yrs of SCI; females 40-50 years old with at
least 10 yrs of SCI;

- Stable SCI (regardless of level of lesion or completeness of injury).

- Ability to sign consent form.

For Optional Fat Meal Test Only

- Must have completed initial risk factor assessment as previously described.

Exclusion Criteria:

- Acute medical illness;

- Pregnancy;

- Chronic debilitating disease (i.e., severe pulmonary disease, stage IV pressure
ulcers, etc.);

- Atrial fibrillation;

- History of percutaneous coronary angiography with stent placement.

For Optional Fat Meal Test Only:

- Known diabetes;

- Lactose-intolerance or dairy allergy;

- Allergy to chocolate.