Coronary Artery Calcification Score and Risk Factors for Coronary Artery Disease in Persons With Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Wounds and Injuries
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Subjects will be recruited from hospital clinics, through advertisements, and referral from
        primary care physicians
      
Biospecimen description: 
      Serum and Plasma
    
Keywords: Coronary Heart Disease; spinal cord injury; risk factor; postprandial lipemia