Dried Blood Spot- Statin Pilot Study
Dried Blood Spot- Statin Pilot Study
Cardiovascular disease (CVD) is the number one cause of mortality for men and women in the
 United States. Dyslipidemia, particularly a high low-density-lipoprotein cholesterol (LDL-C)
 level, is a well-established cardiovascular risk factor and the current American Heart
 Association guideline for CVD risk assessment recommends a lipid panel to be checked. In
 addition, guidelines recommend statin therapy in all patients with clinical atherosclerotic
 CVD, all patients with LDL-C = 190 mg/dL, patients age 40-75 years with diabetes and LDL-C
 70-189 mg/dL, and patients with an estimated 10-year atherosclerotic CVD risk = 7.5%. For all
 of these patients, a fasting lipid panel should be drawn prior to statin initiation as well
 as during follow-up to assess medication and lifestyle adherence. These fasting lipid panels
 are obtained via conventional phlebotomy via venopuncture in an office-based or hospital
 laboratory setting. However, research protein quantitation with mass spectrometry and
 enzyme-linked immunosorbent assay (ELISA) are technologies that allow for sensitive
 quantitation of protein biomarkers and targets, including lipoproteins. Most importantly,
 multiple reaction monitoring (MRM) mass spectrometry is able to assess samples from a dried
 blood spot (DBS), whose advantages include minimal volume requirements, ease of sample
 attainment by finger stick with minimal training required, ease of transport, and sample
 stability.

 The purpose of the proposed analysis is to 1) measure changes in CVD biomarkers before and
 after initiation of statin therapy and 2) compare lipid measurements by conventional
 phlebotomy blood samples to research protein quantitation measurements in DBS and plasma.
Despite reductions in cardiovascular disease (CVD) mortality in the past 20 years, CVD
 remains the leading cause of mortality in the United States, accounting for ~1 of every 3
 deaths. CVD costs the U.S. over $100 billion annually and is an important field for targeted
 primary and secondary prevention. Dyslipidemia, particularly a high low-density-lipoprotein
 cholesterol (LDL-C) level, is a well-established cardiovascular risk factor, and fasting
 lipid panels (including total cholesterol, LDL-C, triglycerides, and high-density-lipoprotein
 cholesterol [HDL-C]) are included in the recent 2013 ACC/AHA Risk Assessment Guidelines.
 Clinical trials have shown that low density lipoprotein cholesterol (LDL-C) reduction with
 statin therapy predicts cardiovascular event reduction. About a quarter of all adults >45
 years old were on statin therapy in 2008, and this will likely increase due to the recent
 2013 ACC/AHA Cholesterol Management guidelines. These guidelines recommend statin therapy in
 all patients with clinical atherosclerotic CVD, all patients with LDL-C = 190 mg/dL, patients
 age 40-75 years with diabetes and LDL-C 70-189 mg/dL, and patients with an estimated 10-year
 atherosclerotic CVD risk = 7.5%. For all of these patients, a fasting lipid panel should be
 drawn prior to statin initiation as well as during follow-up to assess medication and
 lifestyle adherence. These fasting lipid panels are obtained via conventional phlebotomy via
 venopuncture in an office-based or hospital laboratory setting.

 Research protein quantitation with mass spectrometry and enzyme-linked immunosorbent assay
 (ELISA) are technologies that allow for sensitive quantitation of protein biomarkers and
 targets, including lipoproteins. Most importantly, multiple reaction monitoring (MRM) mass
 spectrometry is able to assess samples from a dried blood spot (DBS), whose advantages
 include minimal volume requirements, ease of sample attainment by finger stick with minimal
 training required, ease of transport, and sample stability. DBS sampling has been used for
 clinical and pre-clinical studies, simplifying sample collection and handling. However,
 research protein quantitation with mass spectrometry and ELISA has not been compared against
 conventional blood sample for evaluating changes in cholesterol levels during statin therapy.

 While LDL-C is well-established in predicting CVD event reduction, other laboratory lipid,
 thrombotic and inflammatory biomarkers have been shown to be associated with atherosclerotic
 plaque development or CVD risk. These include Apo A-I, Apo B, Apo E, IgM, plasminogen,
 TIMP-1, Von Willebrand factor, antithrombin III, cystatin C, mesothelin, C-reactive protein,
 SAA, LPS-binding protein, mannose-binding lectin, myeloperoxidase, fibrinogen, alpha-1-acid
 glycoprotein, soluble transferrin receptor, haptoglobin. All of these CVD protein biomarkers
 can be measured by research protein quantitation techniques.

 In a pilot study of 20 subjects, we aim to:

 1. measure changes in a panel of CVD protein biomarkers before and after initiation of
 statin therapy.

 2. compare clinical laboratory measurements of LDL-C and HDL-C in conventional phlebotomy
 blood samples with research protein quantitation mass spectrometry and ELISA
 measurements of LDL-C (Apo B) and HDL-C (Apo A-I) proteins in DBS and plasma.
Inclusion criteria:

 1. Men and women age> 18 years who are initiated on statin therapy in the clinical setting.

 Exclusion criteria:

 1. History of rhabdomyolysis

 2. History of prior allergic reaction to statins

 3. History of liver failure

 4. Contraindications to antecubital phlebotomy or finger stick (including those with
 bilateral dialysis AV fistulae).