Commentary: no smoke without fire-the continuing menace of the betel nut in the world's most vulnerable populations.

In this issue of IJE, McClintock and colleagues describe an association between betel quid chewing and carotid intima-media thickness (IMT) in rural Bangladesh, reporting that betel nut use is associated with subclinical atherosclerosis as manifested through carotid IMT, an effect especially pronounced among men and cigarette smokers. The ancient practice of betel quid chewing is common in many Asian countries and in their diasporas throughout the world. It has widespread social acceptance in many of these societies and importantly is also popular among women. Betel quid chewing has long been recognized as a human carcinogen, in particular resulting in a higher incidence of oral cancers in users. In its most basic form, the ‘betel quid’ is the name given to the small parcels that are made by wrapping areca nuts (the main psychoactive ingredient, commonly called ‘supari’ in India) in a betel leaf (Piper betel) which is then coated with slaked lime(calcium hydroxide). McClintock’s paper tries to move the field beyond oral cancer (the best known downstream adverse clinical manifestation of betel quid) into cardiovascular disease (CVD). The paper is a classic epidemiological treatise, the exposure being measured by an interview conducted by a trained interviewer including a detailed set of questions on the use of betel quid. The outcome of carotid IMT was measured as per international standards, and the study design was that of a cohort. The results certainly imply causation, with duration of betel quid use related to IMT, and are consistent with prior studies suggesting a link between betel nut use and CVD, a field already systemically reviewed and meta-analysed by Paolo Boffetta. Boffetta demonstrated an increased relative risk of fatal myocardial infarction among users of smokeless tobacco products compared with non-users—albeit small at 1.13 (95% confidence interval 1.06-1.21), and hence much lower than the 4-fold or thereabouts increase long quoted for smoked tobacco. McClintock’s paper, which could be criticized for its use of a surrogate marker for CVD, remains a welldesigned study and is conducted in a developing world setting with academic collaboration from a developed world setting, the type of academic partnership that is vital on today’s ever-integrating planet. Given however the extensive literature that exists on the harms of betel quid usage and the numerous reviews already conducted on the subject, perhaps it is pertinent to explore whether this paper will have any impact on policy and whether some of its inferences in the discussion are valid. In particular, the authors write that their findings ‘are of particular relevance in Bangladesh and other Asian populations where betel nut use is prevalent and incidence of CVD is rising’, as ‘countries like it and others are now entering a period where the prevalence of chronic disease is on the rise, coincident with economic development’. This inference is however unjustified. Betel quid usage pre-dates the global CVD epidemic by hundreds of years. Economic development has resulted in widespread urbanization that is associated with an increased uptake of sedentary habits and high-fat diets, risk factors for cardiovascular disease— resulting in a change in disease patterns from predominantly infectious to predominantly non-communicable in developed societies. This pattern of change was originally described by Omran as the ‘epidemiological transition’.