Dried Blood Spot- Statin Pilot Study (DBS)

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.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Hyperlipidemias
• Intervention / Treatment: Other: Dried blood spot testing and phlebotomy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical lipid and research protein measurements (composite)	Compare LDL-C and HDL-C clinical laboratory test measurements in serum vs Apo B and ApoA-I research protein measurements in DBS and plasma as to correlation coefficient across subject samples and level of response (expected reduction) in LDL/Apo B following initiation of statin therapy	up to 4-6 week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker change	Compare biomarker changes Pre- vs Post-statin treatment as observed by LDL-C and HDL-C clinical laboratory tests, research protein measurements in plasma and in dried blood spot	Baseline and 4-6 week follow-up
Research protein measurements in dried blood spot vs plasma	3) Compare research protein measurements of CVD protein markers in dried blood spot and plasma samples to investigate parallelism of results	Baseline and 4-6 week follow-up
Clinical Cardiovascular Risk Score	Compare the research protein measurements of CVD protein markers with the ACC/AHA 10-year atherosclerotic CVD risk score	Baseline

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (ACTUAL): October 1, 2020
• Study Completion (ACTUAL): October 1, 2020

Study Registration Dates

• First Submitted: March 25, 2015
• First Submitted That Met QC Criteria: March 27, 2015
• First Posted (ESTIMATE): March 30, 2015

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Cardiovascular Diseases; Hyperlipidemias
• Other Study ID Numbers: Pro00037026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES