Title:

Alcohol consumption and cardiovascular health in adolescents

The question whether alcohol is protective or a risk factor for cardiovascular disease in adolescents and, if so, where the threshold might be, remains largely unanswered. There are interesting similar behavioural patterns regarding excessive alcohol consumption and overindulgence in eating that leads to obesity, the mechanisms of which are relatively unknown. Marc Schuckit and co-workers have shown that the drinking pattern and level of response to alcohol have values in predicting future heavy drinking and alcohol problems in earlier studies of the ALSPAC cohort (Schuckit & Smith, 2008) as well as other populations (Schuckit & Smith, 2011). Both excessive alcohol consumption and obesity are well- known risk factors for developing cardiovascular disease (Juonala et al., 2009), (Romelsjo, Allebeck, Andreasson, & Leifman, 2012), but the mechanisms and interactions are not easy to investigate in an adult population where the damage is already well established.

Regarding the possibility of a common genetic origin of disease for obesity and alcoholism, there have been few studies with different results. Closely connected to obesity, the FTO rs9939609 genotype has been investigated for association with measures of alcohol consumption, but with inconsistent results (Sobczyk-Kopciol et al., 2011). There are to our knowledge no studies in children, when the epigenetic influence might be less muddled, and therefore present a truer picture of these associations.

Similarly, we know of no previous prospective studies of alcohol consumption and its influence on cardiovascular health, or the connection to obesity, in adolescents of both genders.

Aim:

The ALSPAC - study has investigated cardiovascular risk factors, adiposity, alcohol consumption, a low sensitivity to alcohol (a risk factor for heavy drinking), drinking patterns and drug in children at the ages 9-12 and 17-20.

In the present study our aim is to study cross-sectionally and longitudinally whether alcohol consumption is associated with cardiovascular changes in young healthy adults.

Hypotheses:

We hypothesise that:

1. Alcohol consumption affects cardiovascular risk factors and vascular phenotype:

- cross- sectionally at age 17-20

- with detectable thresholds of alcohol consumption for increased cardiovascular risk or deleterious vascular phenotypes

- with detectable gender differences

We also hypothesise that an earlier onset of alcohol consumption (ages 9-17) relate to the cardiovascular measurements more closely than alcohol quantities and frequencies alone

2. There is an additive effect of alcohol and obesity on cardiovascular risk and vascular phenotype, in the sense that alcohol consumption have an additive relationship to the cardiovascular risk development or adverse vascular phenotype in obese children.

3. That alcohol consumption and obesity are related as measures of common behavioural origins, and that obesity is associated with the sensitivity (i.e., the level of response) to alcohol or alcohol consumption:

- at age 12 or 17 (cross- sectional)

- obesity at age 12 predicts the level of response to alcohol at age 17

- obesity at age 12 predicts the alcohol consumption at age 17

- alcohol consumption at age 12 predicts the development of obesity at age 17

4. That the genetic predisposition to obesity is augmented by alcohol consumption in young.

Exposure variables will be: alcohol intake, level of response to alcohol, duration of alcohol intake, obesity genes.

Outcome variables will be : Cardiovascular measurements: PWV, FMD, brachial distensibility, blood flow, IMT, carotid distensibility, blood pressure and heart rate. Biochemical measurements: IL-6, CRP, Adiponectin, Leptin, Cholesterol, Non-fasting triglyceride. Obesity outcome: BMI, Fat mass.

Confunding variables are: age, gender, heart rate, height, weight, smoking, exercise, medical history, drugs intake.