Cholesterol and Pharmacogenetic Study

Conditions

Cardiovascular Disease, Coronary Heart Disease, Hypercholesterolemia, Hyperlipidemia

Keywords

Statins, Cholesterol, Pharmacogenetics

Brief summary

The overall objective of the CAP study was to determine genetic influences on efficacy of simvastatin treatment with regard to LDL cholesterol reduction and changes in other markers of cardiovascular disease risk.

Detailed description

Despite widespread use of statin therapy for reducing risk of cardiovascular disease risk, there is considerable inter-individual variation in statin efficacy, and it would be desirable to identify markers that would be predictive of the magnitude of beneficial response. The effect of statin most strongly associated with improved clinical outcomes is reduction in LDL cholesterol. The CAP study was a six week non-randomized, open label study of simvastatin 40 mg/day in a group of 335 African-American and 609 Caucasian volunteer subjects. Measurements of plasma lipids and lipoproteins, as well as other markers of cardiovascular disease risk, were obtained at the screening and entry visits, and after four and six weeks of simvastatin treatment. Both baseline measurements and changes in response to simvastatin therapy are being used to test for associations with genetic polymorphisms. Significant findings are being replicated in other study cohorts.

Theusch E, Ting FY, Qin Y, Stevens K, Naidoo D, King SM, Yang NV, Orr J, Han BY, Cyster JG, Chen YI, Rotter JI, Krauss RM, Medina MW.

2024-07-262 citations

10.1186/s13073-024-01366-9

Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment.

Trupp M, Zhu H, Wikoff WR, Baillie RA, Zeng ZB, Karp PD, Fiehn O, Krauss RM, Kaddurah-Daouk R.

2012-07-0972 citations

10.1371/journal.pone.0038386

Genome-wide association of lipid-lowering response to statins in combined study populations.

Barber MJ, Mangravite LM, Hyde CL, Chasman DI, Smith JD, McCarty CA, Li X, Wilke RA, Rieder MJ, Williams PT, Ridker PM, Chatterjee A, Rotter JI, Nickerson DA, Stephens M, Krauss RM.

2010-03-22182 citations

10.1371/journal.pone.0009763

Interventions

DRUGSimvastatin

40mg/day

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

30 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* at least 30 years of age * Total Cholesterol between 160 to 400 mg/dl * \> 3 grandparents of African-American descent or \> 3 grandparents of Caucasian descent * serum triglycerides \< 400 mg/dl * fasting glucose \< 126 mg/dl

Exclusion criteria

* Use of lipid-lowering medication * Use of over-the-counter products containing sterol or stanol esters or fish oil * Recent or planned change in dietary intake or weight change of more than 4.5 kg * Use of corticosteroids, immunosuppressive drugs or drugs affecting the CYP3A4 system * Known liver disease or elevated transaminase levels * Elevated creatine phosphokinase levels \> 10 times upper limits of normal * Uncontrolled blood pressure, or diabetes mellitus * Abnormal renal or thyroid function * Current alcohol or drug abuse * Major illness in the preceding three months * Pregnancy * Know intolerance to statins * Racial ancestry other than African-American or Caucasian

Design outcomes

Primary

Measure	Time frame
Triglycerides	-2, 0, 4, 6 weeks
C-reactive protein	-2, 0, 4, 6 weeks
HDL Cholesterol	-2, 0, 4, 6 weeks
Total Cholesterol	-2, 0, 4, 6 weeks
LDL Cholesterol	-2, 0, 4, 6 weeks

Secondary

Measure	Time frame
Apolipoprotein CIII	-2, 0, 4, 6 weeks
LDL Peak Particle size	-2, 0, 4, 6 weeks
LDL Subfractions	-2, 0, 4, 6 weeks
Total Cholesterol/HDL Cholesterol	-2, 0, 4, 6 weeks
Apolipoprotein B	-2, 0, 4, 6 weeks
Apolipoprotein AI	-2, 0, 4, 6 weeks

Countries

United States

Outcome results

None listed