South Asians, ethnicity and cardiovascular disease:no easier to unravel than genetics
South Asians (people from India, Pakistan, Bangladesh, Nepal, Maldives and Sri Lanka) seem to have high rates of heart attacks and stroke (collectively known as cardiovascular disease) that is not explained by widely-known risk factors such as high blood pressure or smoking. When you consider that the Indian subcontinent accounts for over 1.4 billion people and carries the greatest global burden of cardiovascular disease, it is important to understand what puts these people at increased risk, even when they migrate to other countries.
I have spent this week at Northwestern University in Chicago, learning about their great programme of clinical research into the causes of cardiovascular disease. I heard of my favourite ever acronym for a study, “MASALA” (The Mediators of Atherosclerosis in South Asians Living in America) which is recruiting 1000 South Asians in Chicago and San Francisco and will compare risk factors and development of heart disease. Interestingly, whereas study of South Asians has been at the forefront of research regarding ethnicity and cardiovascular disease in the UK, study of ethnic disparities in health has tended to focus on African American populations.
It is well-known that risk of stroke and risk of heart disease are linked to socio-economic status. In a London-based study of 1400 South Asian men, deaths from heart attacks and stroke were more likely in men whose fathers had “manual” occupations, or in men who had completed less than 11 years of formal education. This effect was more marked in men who themselves were engaged in manual work, and the authors concluded that “childhood socioeconomic position”, together with adult socioeconomic position cumulatively influenced the risk of dying of from cardiovascular disease. Studies in Scotland have shown similar results. There is definitely a relationship with socioeconomic deprivation and heart disease in Indians living in India How do we best measure “social disadvantage”? Do we need a “social disadvantage index”, as has been proposed by Canadian researchers led by Salim Yusuf? They found that social disadvantage was higher among older people, women, and non-white ethnic groups. The jury is still out regarding the best way to measure socioeconomic status, but it does appear that ethnic minorities, including South Asians, tend to suffer from a greater degree of social deprivation, which may contribute to cardiovascular disease. However, results of the 2010 US census show that Indians living in America have higher income than other ethnic groups and are the fastest growing ethnic minority, so socioeconomic status is not telling the whole story about the high rates of cardiovascular disease in America.
What about migration? The Indian Migrant Study and other studies suggest that South Asians who migrate within their countries from rural to urban areas, as well as those who move to Western countries, seem to have increased risk of heart attack and stroke, and there seem to be roles for socioeconomic status, risk factors and migration itself.
In the UK, one study has shown higher reported “psychosocial adversity” in South Asians who had suffered heart attacks, compared with UK whites, in terms of greater chronic stress, in the form of financial strain, residential crowding, family conflict, social deprivation and discrimination, despite larger social networks. These effects were largely independent of socioeconomic status. Linguistic and cultural barriers have been previously cited as potential causes of higher rates of heart attacks in South Asians, but it is not as simple as that, as Hindus and Sikhs were more likely to seek help for chest pain than their white European counterparts in one study.
Lifestyle is also likely to be very important and many differences seem to manifest in early childhood, such as lower physical activity in South Asians and higher saturated fat intake in Indians.
Last year, I wrote about research looking at ethnicity and risk of stroke in the UK and the USA. As I said then, the research continues to describe differences in traditional and non-traditional risk factors, but not so much has been done to design and implement interventions to reduce the variations in health due to ethnicity. The interplay of environmental factors and ethnicity in cardiovascular disease is no less complex than the interplay of genes and environment. Encouragingly, the discourse about the best policies to tackle health disparities related to ethnicity is well underway on both sides of the pond.
Publication bias: big problem for children
A recent study in the journal Pediatrics reported that only 29% of clinical studies in children have been published. This finding reinforces previous studies that there is significant publication bias in paediatric studies. These findings are a cause for serious concern.
What is publication bias? Essentially, it is the selected publication of studies based on the results, such as only publishing studies that demonstrate a drug works while not publishing studies that demonstrate harms.
Publication bias is a serious problem in healthcare and can have a large influence on treatment decisions by only providing limited information. Researchers have demonstrated substantial publication bias in certain areas such as the antidepressant medication reboxetine.
Several initiatives have been spearheaded to help reduce publication bias. The creation of open-access journals have shifted the focus from the importance of the results (as judged by a journal editorial committee) to the methodological rigour by which the study was completed.
But more importantly has been the creation of online trial registries, such as ClinicalTrials.gov launched in 2000. These registries serve as central databases of all the current and on-going clinical studies. Registration is optional, however in 2005 the ICMJE made registration of clinical trials as a pre-requisite of publication. Although this does not represent all journals, it sent a strong message of the importance of registration.
However despite the creation of trial registries, less than half of US based National Institute of Health (i.e. government) funded trials in children were registered on ClinicalTrials.gov. Another important finding was the lack of information included on the registries. One-third of all clinical studies terminated early did not provide any information about why they were stopped. The situation was similar for suspended studies with one quarter not providing information.
Were these studies stopped because of harms? Were the investigators no longer able to recruit children to enroll? Whatever the reason the studies were stopped, this information must be made public.
Registration of all clinical studies involving children must be made mandatory. This is the only way to minimise publication bias and increase the reporting of research. This would create massive industry uproar, but is it ethical to enroll children in a clinical study without having it publicly registered? At a minimum any trial that receives government funded must be registered.
However registration of studies is only one element of the formula. What about the dissemination of the results? Less than 10% of completed studies in children had results posted and publicly available. With the low publication rates of registered studies, and the even lower rate of posting results, how much information is still missing?
Indeed progress has been made to increase the quality and transparency of clinical studies in children but more is needed. We cannot assume that because trial registries exist that they are being used. Complacency must be replaced with compliance. It seems that more often than not, the little ones have the biggest problems.
Increasing access to journals through peer reviewers
A recent letter to the editor in the Canadian Medical Association Journal (CMAJ) highlighted a potential opportunity to increase access to subscription-based journals for individuals in low and middle-income countries. It turns out that a few journals give their peer reviewers’ free journal access or a free subscription as a thank you gift for their effort.
How widespread is this policy in the medical publishing world?
Unfortunately not very. Of the 21 journal editors contacted (including CMAJ, Lancet, BMJ, JAMA, etc.), only three actually provide reviewers with free journal access. The gift ranges from a 3-month (Lancet) to a 12-month subscription (BMJ and the Journal of Intellectual & Developmental Disability).
On the positive side, 20 out of the 21 journals were members of the Health InterNetwork Access to Research Initiative (HINARI), the World Health Organisation’s programme to provide free or low cost online access in the developing world to scientific research. This is encouraging, but HINARI is not perfect and many are still left without access.
For example, a BMJ Rapid Response highlighted that health care workers in middle-income countries such as Malaysia are often caught in the middle. Too rich for aid but not wealthy enough to afford the high cost of journal subscriptions.
However, despite the fact that most original research relevant to low and middle-income countries is open-access, the majority of the education articles, clinical reviews, news pieces and commentaries are still often behind firewalls that require payment.
The move for more open-access journals is encouraging. For example, the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust will be launching eLife, a new open access journal later this year.
Why don’t more journals provide peer reviewers with free subscriptions? Not only is it a symbol of appreciation for the hours of gratuitous time altruistically invested but it could be used to help others. Likely there is no pressure or demand for it. The majority of peer reviewers are already at academic institutions with subscriptions.
Has this happened to you before? What have you done with this free gift? Although few journals seem to be endorsing this policy, it may serve as a small way to increase access to those who otherwise do not have it.
In the future, if you review an article for the BMJ, the Lancet or the Journal of Intellectual & Developmental Disability (or other journals that provide free subscriptions after peer reviewing), rather than deleting the email consider who might benefit.
If you review for a journal that does not, ask the editor why not?