Cardiovascular Disease Biomarkers in Smokers and Moist Snuff Consumers
Condition: Cardiovascular Disease; Cigarette Smoking
MeSH terms: Cardiovascular Diseases
Study type: Observational

Summary: 
      This cross-sectional study was primarily a cardiovascular disease (CVD) study designed a) to
      compare selected CVD biomarker data between subjects who were long-term consumers of
      cigarettes or moist snuff and non-consumers of tobacco and b) to identify principal endpoints
      related to CVD risk that differed among the three tobacco-use cohorts. The following
      assessments provided the primary study endpoints for comparative analyses between the
      cohorts:

        1. CVD-related physiological assessments: Flow-mediated dilation (FMD), carotid
           intima-media thickness (CIMT), ankle-brachial index (ABI), spirometry and expired carbon
           monoxide (ECO).

        2. CVD-related biomarker assessments in blood and urine (biomarkers of tobacco effect).

        3. Biomarkers of tobacco exposure in urine and blood.
    

Detailed description: 
      This single site, observational study will provide an increased understanding of how
      consumption of different tobacco products (i.e., cigarettes and moist snuff compared to no
      tobacco use) affects 1) CVD-related physiological assessments and 2) CVD-related biomarkers
      of tobacco effect (i.e., proteins, lipids, and cellular components). A recent policy
      statement from the American Heart Association provides a review and analysis of the impact of
      smokeless (ST) use on cardiovascular disease (CVD) (Piano et al. 2010). The authors
      acknowledge that the evidence is consistent with the suggestion that the cardiovascular risks
      from ST products are markedly lower than those from cigarette smoking. Despite the potential
      risk reduction in transitioning from cigarettes to ST consumption, few studies have directly
      compared biomarkers of tobacco effect (BioEff) among smokers, moist snuff consumers (MSC) and
      non-tobacco consumers (NTC).

      Furthermore, this study will measure biomarkers of tobacco exposure to assess their ability
      to differentiate the three tobacco consumer groups (smokers, moist snuff consumers,
      non-tobacco consumers) based on product use. Estimating exposures to combustion-related
      compounds found in tobacco smoke is best accomplished using biomarkers. A key advantage of
      human exposure biomarkers is that they are considered reliable metrics of the levels of
      exposure that consumers actually experience when using tobacco products (Hecht et al., 2010).
      Because combustion does not occur during ST use, ST products lack most of the
      combustion-related compounds found in tobacco smoke. Biomarker differences found between
      different tobacco use groups to harmful or potentially harmful constituents may indicate
      differences in subsequent health risks (Rodu and Godshall, 2006; Hatsukami et al., 2006).

      Epidemiological data demonstrate that the health risks associated with cigarettes are
      significantly greater than those associated with the use of non-combustible tobacco and
      nicotine products (Surgeon General, 2010). On a relative risk continuum, cigarette smoking
      presents a significantly greater risk to tobacco users than use of non-combustible smokeless
      products. ST products, which are consumed orally, do no generate chemicals associated with
      the burning of tobacco, and thus, present a reduced toxicant profile compared to smoking.

      To address the purpose and objectives of this study, the study was conducted as follows:

        -  Subjects were consented for the study prior to any procedures being performed and
           screened on study-specific inclusion/exclusion criteria to determine subject eligibility
           (within 28 days of study check-in).

        -  Eligible subjects were admitted to the clinical research unit between 12:00 noon and
           5:00 p.m. on Day 1 and confined for one overnight stay (approximately 18-23 hours).

        -  After all study procedures were completed on Day 1 and Day 2, appropriate basic safety
           assessments were made and subjects were discharged approximately at 12:00 noon on Day 2.

      A brief description of the study procedures performed is listed below.

        -  After check-in on Day 1, eligible subjects observed a 45-minute tobacco abstention
           period, followed by use of a single unit of their usual brand (UB) tobacco product,
           referred to as a "Challenge." For smokers, the "challenge" was smoking one UB cigarette
           in their usual manner; for moist snuff consumers, a 30-minute use of one typical pinch
           of their UB moist snuff.

        -  Fifteen minutes after the end of UB use, the following procedures were performed
           sequentially: ECO; blood samples for biomarkers of exposure (serum nicotine and
           cotinine, percent carboxyhemoglobin in whole blood); and ABI.

        -  At 30 minutes post-UB use, FMD was measured followed by administration of health-related
           questionnaires. The non-tobacco consumers had no product "Challenge". The completion of
           study questionnaires served as the reference point for collection of ECO, ABI and FMD.

        -  Blood biomarkers of tobacco exposure were collected on Day 1 following product
           "Challenge" and on Day 2 following an overnight tobacco abstention and fast.

        -  Urine biomarkers of tobacco exposure and effect were collected on both Day 1
           post-"Challenge" and on Day 2 fasting.

        -  Blood biomarkers of tobacco effect were only collected on Day 2 fasting, followed by the
           re-assessment of the physiological measures (ECO, ABI, FMD) and assessment of CIMT.
    

Intervention name(s): Subject's usual brand (UB) tobacco product
Intervention type(s): Other
Intervention description(s): For SMK: UB of cigarettes; For MSC: UB of moist snuff
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects were selected from a community sample of male smokers, moist snuff consumers and
        non-tobacco consumers. Target enrollment was 60 subjects/cohort (N=180).

        The age-stratification for each of the three cohorts was as follows:

          -  Ages 26 to 31: n=15

          -  Ages 32 to 37: n=15

          -  Ages 38 to 43: n=15

          -  Ages 44 to 49: n=15
      
Biospecimen description: 
      Biospecimens to be retained include: serum, plasma, and urine.
    
Keywords: Flow mediated dilation; Carotid intima-media thickness; Ankle-brachial index; Smokeless tobacco; Biological markers; Nicotine; Tobacco-specific nitrosamines; Polycyclic aromatic hydrocarbons; Aromatic amines; Mercapturic acid metabolites; Cholesterol; Blood lipids; Oxidative stress; Inflammation; Cytokines