EAL

SCI: Lipid Abnormalities (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To describe the relationship of hsCRP (high-sensitivity C-Reactive Protein) with CVD (cardiovascular disease) risk among persons with SCI (spinal cord injury) by studying this marker in individuals with insulin resistance and/or metabolic syndrome.

Inclusion Criteria:

A convenience sample of 93 person with SCI were recruited through the Veterans Administration (VA) system and the local community.

Exclusion Criteria:

Individuals without established SCI.

Description of Study Protocol:

Recruitment

A sample of 93 persons with SCI injury were recruited through the local VA and in the local community.

Design

Cross-sectional analysis

Blinding used (if applicable)

N/A

Intervention (if applicable)

N/A

Statistical Analysis

All statistical analyses were performed using NCSS 2001 software (NCSS, Kaysville, UT).
Unpaired t tests were used to determine statistical differences in hsCRP, lipids, insulin, or obesity measures attributable to insulin resistance or metabolic syndrome.
In addition, unpaired t tests were performed to determine if hsCRP or HOMA insulin resistance scores were different in subjects with elevated Framingham risk >6).
Linear regression was used to study associations between hsCRP and the obesity measures, HOMA insulin resistance, and lipid values.

Data Collection Summary:

Laboratory Data

Participants were asked to fast for 12 hours prior to blood sampling.
Severe dyslipidemia was defined as the presence of 4 or more abnormal lipid values. Lipids were considered abnormal for TC > 200 mg/dL, triglyceride > 150 mg/dL, HDL < 40 mg/dL, LDL > 130 mg/dL, and TC:HDL ration > 4.9.
hsCRP was analyzed using a Dade Behring nephelometer (BN II) (Newark, DE) in milligrams per liter.
High-sensitivity measurements were only obtained when the CRP screen was <0.8 mg/dL, as values >0.8 mg/dL indicate clear infection.

Relative risk categories for hsCRP were taken from estbalished population studies of cardiovascular risk associated with atherogenic inflammation in men, women, middle-aged, and the elderly.

C-reactive protein risk categories divided into quintiles with the range given in mg/dL
Rank	Quintile	CRP range
Lowest Risk	1	<0.7 mg/L
Mild Risk	2	0.7-1.1 mg/L
Moderate risk	3	1.2-1.9 mg/L
High Risk	4	2.0-3.8 mg/L
Highest Risk	5	3.9-15 mg/L

In accordance with the National Cholesterol Education Program Adult Treatment Panel III guidelines, metabolic syndrome was defined as the presence of 3 or more metabolic disorders, including hypertension, obesity, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol.
Hypertension was defined as either systolic blood pressure >/= 130 mmgHG, diastolic pressure >/= 85 mmHg, or the use of antihypertensive medications.
Men with a waist circumference of >/= 102 cm and women with a waist circumference of >/= 88 cm were considered obese.
A fasting glucose >/= 110 mg/dL or presence of glucose lowering medications indicated the presence of hyperglycemia.
Hypertriglyceridemia was considered present if the fasting serum triglyceride level was >/= 150 mg/dL or if the participant was taking cholesterol-lowering medications.
Serum HDL <40 mg/dL for men and HDL <50 mg/dL for womenwere considered low, and subjects onfholesterol-lowering medications were also considered to have low HDL for the purpose of determining presence of metabolic syndrome.
The Framingham risk score was determined using well-known characteristics, including gender, age, total cholesterol, HDL cholesterol, systolic blood pressure, and history of diabetes and smoking.

Description of Actual Data Sample:

Initial N: 93 persons (13 women and 80 men) with SCI

Attrition (final N): 93 participants

Other relevant demographics and anthropometrics:

39 persons with tetraplegia and 54 persons with paraplegia
34 subjects (36.6%) reported a history of chronic infection, 54 subjects (58.1%) had a history of smoking, and 8 subjects (8.6%) had a family history of coronary artery disease.
Metabolic syndrome was present in nearly one-quarter of the study population (22.6%).
Diabetes was present in more than one fifth of the subjects (21.5%).
11% of subjects were insulin resisant when relying entirely on mean fasting glucose and insulin values; however, when medicaitons were taken into consideration, 22% of the subjects were insulin resistant.

Summary of Results:

A substantial proportion of the subjects had elevated hsCRP levels, placing them in the highest risk quintile for CVD as established by large groups of ambulatory subjects.
Researchers did not observe a direct association between hsCRP and individual lipids, however, the mean hsCRP levels were considerably higher for individuals with 4 or more abnormal lipid values.
The concordance of hsCRP with high Framingham Risk and/or subjects with SCI who have a history of smoking and/or drinking suggests a link between elevated hsCRP and increased risk of heart disease in the SCI population.

Other Findings

Levels of hsCRP were not significantly different in subject who reported a history of chronic infection (P=0.28), smoking (P=0.89), family history of coronary artery disease (p=0.31), diabetes mellitus (p=0.28)or in active indiciduals (those engaging in aerobic activity for at least 30 minutes, 3 times per week) (P=0.84).
Levels of hsCRP were significantly higher in subjects who consumed 2 or more drinks per day (P<0.05),
Classifying subjects with SCI by injury or American Spinal Injury Assocation (ASIA)/Frankel classification did not reveal significant differences in mean hsCRP.

hsCRP Risk Quintiles

The mean hsCRP level in persons with SCI (2.37+/- 2.14 mg/L) was equivalent to fhr fourth quintile (high-risk group).
The mean hsCRP of subjects with metabolic syndrom corresponded with the high risk quintile.
When individuals who were taking cholesterol-lowering medications were removed from the analysis, subject characterized with metabolic syndrome had a 2.5-fold higher mean hsCRP value, placing them in the highest risk quintile.
Insulin resistant individuals with SCI had significantly higher mean hsCRP (P<0.05) that placed them in highest risk quintil compared with subjects who were insulin sensitive.

Lipids

There was no apparent trend in lipid values relative to level of injury, ASIA impairment, or duration of injury.
hSCRP correlated poorly with the individual lipid values.
When subjects were categorized with severe dyslipidemia vs fewer abnormalities, there was a marked increase in hsCRP (P<0.001).

Framingham Risk

hsCRP was considerably higher (P<0.05) among subjects with SCI with a Framingham Risk Score of >/= 6.
Subejcts with both metabolic syndrome and a threshold CRP level had nearly double the Framingham Risk Score compared with subjects without the 2 conditions (P<0.05); given the mean age of the SCI study group, subjects with both conditions had a 114% higher 10-year risk of developing coronary heart disease.

Metabolic Syndrome and Insulin Resistance

Prediabetic individuals with SCI did not have a significantly higher hsCRP than their healthier counterparts (P=0.60), however, when subjects who were taking cholesterol lowering medication were removed from the analysis, mean hsCRP was significantly eleveated (P<0.05).
In addition to increased Framingham Risk, prediabetic subjects had significantly higher HOMA insulin resistance (P<0.001) compared with non-pre-diabetic subjects.
There was a mild assocation between increased hsCRP and HOMA insulin resistance values in the SCI group (r=0.33, P<0.05), which was strengthened when subjects who were on cholesterol medicaitons were removed from this cohort (r=0.57, P<0.001).

Diabetes Mellitus

Obesity measure and the Framingham Risk were significantly higher in diabetic subjects (P<0.05), hsCRP was not elevated.

Author Conclusion:

Findings suggest that elevated hsCRP is associated with increased cardiac risk among individuals with SCI.
The use of hsCRP in addition to the presence of other risk factors, such as metabolic syndrome and insulin resistance, should help improve the identificaiton of individuals within the SCI population who are at risk of developing CVD.
Evidence of elevated hsCRP values in this high-risk population supports the use of hsCRP as an indicator of heart disease risk.

Funding Source:

Government:

VA Rehabilition Research and Development Service

Reviewer Comments:

Rather small sample size and incomplete discussion of limitations, but overall authors demonstrated research goal.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	N/A
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	N/A
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		???
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	No
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	N/A
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	No
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes