Alcohol Consumption and Arterial Stiffness: A Longitudinal Study of Pulse Wave Velocity in the Whitehall II Cohort
Condition: Aortic Stiffness
Study type: Observational

Summary: 
      Arterial stiffness is an important marker of cardiovascular health. Recent evidence from
      cross-sectional research has suggested it is associated with alcohol consumption. Research
      that employs a longitudinal perspective may be better equipped to evaluate the nature of this
      relationship and in particular to determine whether alcohol consumption is linked to the
      progression of arterial stiffness over time. The current study will consequently implement a
      longitudinal cohort design to evaluate the association between long-term alcohol consumption
      patterns and changes in arterial stiffness. Data will be drawn from the Whitehall II cohort
      study of British civil servants, in which participants completed repeat pulse wave velocity
      (PWV) assessments of arterial stiffness across a four-to-five year interval. Repeat
      measurements of volume of alcohol intake were also recorded for participants, extending back
      across more than two decades. Intake will be categorised in such a way as to distinguish
      between different alcohol consumer types, including non-drinkers and former drinkers. Linear
      mixed effects models will be used with adjustment for potential confounds, such as age,
      diabetes, mean arterial pressure and heart rate. Results from the modelling work will
      illustrate the extent and form of the association between alcohol intake and PWV. This work
      will provide useful insights into the role that alcohol intake plays in the longitudinal
      progression of an important cardiac marker, and it will have implications for our
      understanding of alcohol's relationship to cardiovascular health in the general population.
    

Detailed description: 
      Arterial stiffness occurs where the vessel wall lacks elasticity. It is known to be
      independently associated with both cardiovascular morbidity and mortality, such that it can
      act as a surrogate end point for studies of cardiovascular disease. Pulse wave velocity (PWV)
      is an index of this stiffness and has been described as its 'gold standard' measurement.

      A number of other clinical factors have been found to show meaningful association with PWV,
      including heart rate and mean arterial pressure. These findings have highlighted the need for
      studies of new potential determinants of PWV to account for the potentially confounding
      influence of these known factors. Additional demographic and lifestyle characteristics have
      also been shown to act as moderators of PWV. In particular, research has demonstrated that
      PWV increases with age, and this stiffness is consequently deemed an indicator of vascular
      ageing.

      Alcohol intake is another lifestyle characteristic that has been considered as a potential
      factor in the loss of arterial elasticity. Evidence to date suggests that a J-shaped
      association may exist between such intake and PWV, but this work has mostly relied on
      cross-sectional data or looked at short-term intake patterns only. By adopting a longitudinal
      perspective, further insight may be garnered into this important epidemiological issue.
      Consequently, the new study herein proposed will address this research need and investigate
      how different patterns of alcohol consumption relate to arterial stiffness and to the
      progression of this stiffness over time. The primary objectives of this study are to (1)
      examine whether long-term patterns of alcohol consumption are independently associated with a
      baseline assessment of carotid-femoral PWV and (2) whether alcohol intake is likewise
      associated with longitudinal changes in this important cardiovascular marker.

      Longitudinal alcohol exposure will be determined from reported consumption at phases 1
      (1985-1988) through 9 (2007-2009) of the Whitehall II Cohort Study and categorised according
      to the latest UK recommendations on alcohol intake limits. These guidelines define moderate
      consumption as weekly ethanol intake volumes of 112g or under for both males and females. As
      alcohol consumption is recorded in UK units in the Whitehall II database, conversion will be
      performed using the standard ratio of 1 unit to 8 grams of ethanol prior to categorisation.
      The subsequent categorisation will draw distinctions between non-drinkers and former
      drinkers, as well as between moderate and heavy consumers. Those with unstable patterns of
      consumption will also be identified as there is emerging evidence that such consumers may
      have a different cardiovascular risk profile compared to consumers with more longitudinally
      consistent intake patterns.

      Demographic and clinical characteristics will be investigated to provide context for the
      subsequent inferential analyses. As research has also suggested that participant sex can
      moderate the relationship between alcohol and PWV, this will be tested in the current
      analysis (through preliminary modelling that includes sex as part of an interaction term with
      level of alcohol consumption). If this moderation effect is replicated, then our core result
      reporting will be stratified according to sex.

      Linear mixed effects models will then be used to examine the effect of long-term alcohol
      consumption on PWV and its effect on subsequent longitudinal changes in this cardiovascular
      marker. This modelling approach is particularly suited to analysing the complex data
      structure under investigation, including the correlation across individual participants'
      paired measurements. A detailed analytic protocol is available upon request.

      Supplementary linear mixed effects modelling will also be performed to look at the
      association between short-term alcohol consumption patterns and PWV. This will employ the
      same modelling strategy as used in the primary analysis above, with the categorisation of
      consumption utilising reported intake at the most recent assessment phase only. This
      supplementary analysis will offer additional context for the findings of the primary analysis
      and provide further detail on the relationship that different forms of alcohol consumption
      have with arterial stiffness.

      Through this comprehensive and detailed analysis, it is hoped that new insights on this
      important issue of cardiovascular health will be obtained.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Data will be drawn from the Whitehall II cohort study database. This incorporates
        longitudinal assessments of 6,895 male (67%) and 3,413 female British civil servants,
        originally recruited between 1985 and 1988. The overall age range was 34 to 56 years. Of
        these, 897 were excluded due to having a history of cardiovascular disease. Clinical
        assessments were repeated at 4-to-5 year intervals. PWV measurement was introduced to the
        protocol at phase 9, with assessments taking place during 2008 and 2009. 3,869 of the
        sample participants had a successful PWV assessment during this time. Follow-up testing
        took place at phase 11, during 2012 and 2013. Of the participants who underwent a PWV
        assessment at phase 9, 3,130 also had a successful PWV assessment at phase 11. This group
        included 2,350 males (75%) and 780 females.
      
Keywords: Alcohol; Aortic stiffness; Arterial stiffness; Pulse wave velocity; Longitudinal