Associations with BMI and cigarette smoking

There is a well-established association between ADHD and obesity (obesity defined as BMI ≥30 kg/m²).^{Reference Cortese, Moreira-Maia, St Fleur, Morcillo-Peñalver, Rohde and Faraone16} Genetic overlaps between ADHD and BMI have also been well documented^{Reference Peters, Nüllig and Antel18} and a recent study using two-sample Mendelian randomisation suggests, using genetic variants, a bidirectional causal relationship between ADHD and childhood obesity.^{Reference Leppert, Riglin and Wootton7} We found a robust association between childhood ADHD problems and obesity but not between ADHD problems and overweight status. Interestingly, we only found elevated BMI in mid-life, not in childhood and adolescence. This suggests that adult psychiatrists need to monitor obesity status in particular.

Childhood ADHD was also associated with cigarette smoking in mid-life. Again, this link between smoking and ADHD is well established, with evidence suggesting that associations over the longer term may arise because of nicotine dependence linked to self-medication^{Reference van Amsterdam, van der Velde, Schulte and van den Brink19} and increased likelihood of experiencing nicotine withdrawal effects such as irritability and difficulty concentrating on stopping.^{Reference Pomerleau, Downey, Snedecor, Mehringer, Marks and Pomerleau20} Genetic studies also have found evidence for genetic overlap between substance use disorder (including cigarette smoking) and ADHD.^{Reference Vilar-Ribó, Sánchez-Mora and Rovira21} This is the first study to report mid-life smoking outcomes for individuals with ADHD symptoms assessed in childhood.

Associations with blood pressure

Hypertension is the most important risk factor for coronary artery disease^{Reference Yusuf, Joseph and Rangarajan8} and the risk seems most pronounced for elevated systolic blood pressure.^{Reference Kannel15} To our knowledge, no prospective studies have followed up children with ADHD or ADHD symptoms to examine blood pressure in mid-life. As medication used to treat ADHD has the propensity to cause elevated blood pressure, several studies have followed up children with ADHD on medication into early adulthood to check whether blood pressure becomes elevated; their findings are mixed, but a recent review has concluded that there is evidence for a slight elevation (3–8 mmHg) in systolic blood pressure.^{Reference Fay and Alpert22} The individuals in our study were born in 1958. Medication for childhood ADHD was first approved in the 1960s but UK prescribing was relatively low until around 2000.^{Reference Renoux, Shin, Dell'Aniello, Fergusson and Suissa23} Most individuals in our study would therefore not have been prescribed any medication for ADHD during childhood and adolescence. It is intriguing that, given our study findings, probably untreated childhood ADHD is also associated with a modest elevation of blood pressure in mid-life (age 44). Our study further elaborates recent studies on younger populations which found that untreated ADHD is associated with low blood pressure in late adolescence^{Reference Garcia-Argibay, du Rietz, Hartman, Lichtenstein, Chang and Larsson24} but that this finding does not persist into young adulthood.^{Reference Schulz, Huber and Schlack25} This would suggest the need to examine mechanisms that lead to the increase in blood pressure through adulthood for individuals with ADHD and the need for caution in interpreting any findings from more recent cohorts that focus on examining the long-term effects of medication for ADHD on blood pressure.

Associations with cardiovascular risk and disease

Although there is growing recognition of the importance of cardiovascular disease and CVD risk factors in those with psychiatric disorders, especially depression, neurodevelopmental disorders such as ADHD that typically first manifest in childhood have often been ignored. Recent large-scale patient registry and clinical studies have suggested that clinically diagnosed ADHD is associated with cardiovascular diseases, but we do not know whether this is because of obesity and cigarette smoking alone. Our prospective study suggests that childhood ADHD problems in the general population are associated with multiple cardiovascular risk factors in mid-life. The findings from this study when taken together with clinical and registry-based studies highlight the importance of monitoring cardiovascular risk profiles in those with ADHD to prevent later CVD. Few psychiatrists will be trained in using CVD risk calculators and primary care physicians may not recognise people with ADHD as benefitting from repeated physical health checks.

Systolic blood pressure, sex and SES

ADHD and systolic blood pressure are known to be associated with both sex and socioeconomic status. Sensitivity checks were conducted to examine males and females separately and higher and lower SES at birth. These suggested that the relationship between ADHD and systolic blood pressure is attenuated by sex; we observed the same attenuation for SES at birth. We did not detect robust evidence that the association between ADHD and systolic blood varied by sex or SES at birth. However, given the small sample size, there is a need for caution in interpreting these results, especially given robust evidence of elevated cardiovascular disease rates in those with ADHD in larger patient registry data, regardless of sex and SES.^{Reference Bowerman and O'Connell26}

Strengths and limitations

Although this study benefits from using a population-based birth cohort followed up until mid-life with repeated direct assessments there are some limitations. In common with most population cohorts, there is some loss to follow-up, which leads to some missing data. However, results using multiple imputation were very similar to those for the primary analysis, although data on which to base imputations were limited, as were detailed data on medications and healthcare use. Another limitation was that ADHD assessment during childhood in the 1960s was limited to the Rutter Scale. The NCDS includes only two questions, with a focus more on the hyperactive rather than the inattentive domain – a decision that might have seemed appropriate at that time. However, both parent and teacher ratings were available and used for the categorisation, the questionnaires have been validated against diagnoses and our prevalence rate of broadly defined ADHD (3%) is not dissimilar to rates observed using diagnostic interviews. It is now known that childhood ADHD symptoms and impairment persist in most individuals into adult life and that adult ADHD requires clinical attention.^{Reference Caye, Swanson and Thapar27} However, the NCDS like many other population cohorts and volunteer cohorts, such as UK Biobank, has never included any measures of adult ADHD. Other limitations are that until information from this cohort at an older age is available, it is not possible to replicate recent health registry findings on ADHD diagnosis and CVD associations. However, the registry studies are unable to directly examine CVD risk factors, which we were able to do. Moreover, triangulation of findings on CVD and CVD risk from patient-based registry studies, genetic studies^{Reference Wilson28} and now a population cohort study provides greater confidence in conclusions across these different designs.

Implications

As noted, childhood ADHD problems are associated with higher levels of multiple risk factors in mid-life that are particularly associated with the development of CVD.^{Reference Wilson28} However, individuals with ADHD may be less likely to consult a primary care physician about their physical health and may therefore be less likely to have the opportunity to discuss the benefits of preventive strategies, including lifestyle measures and interventions such as treating hypertension and hyperlipidaemia. Also, monitoring physical health may not be a priority for adult mental health services. For example, guidance on managing ADHD from the UK's National Institute for Health and Care Excellence does not mention the need for physical health screening in adulthood unless related to medication.²⁹ This study adds to the literature in highlighting the importance of considering physical and mental health together with neurodevelopmental disorders. Taking all the findings across different studies together, CVD risk monitoring and early prevention of CVD should be part of follow-up for individuals with a history of ADHD, given that CVD risk factors are amenable to intervention.