Macrovascular Residual Risk Studies

COMMENT

Increased BMI is a well-recognised cardiovascular risk factor.(1) Adiposity can increase blood pressure and predispose to dyslipidaemia, inflammation and the development of insulin resistance and type 2 diabetes. Not surprisingly, the world-wide escalation in obesity rates has led to justifiable concerns about the corresponding impact on prevalence of cardiometabolic disease. Indeed, a particular cause for concern is the Latin America region, where obesity and related cardiometabolic disease are now the most important public health concern; by 2040, Brazil is anticipated to ‘top the global league’ for cardiovascular mortality.(2)

Furthermore, increased BMI counters the established benefits of effective strategies targeting high blood pressure, cholesterol and blood glucose. In this study, being overweight was associated with 50% excess risk of CHD and 98% excess risk of stroke compared with individuals with normal weight with targeted treatment of these three mediators of risk. This finding clearly argues for sustained intervention at the public health levels to address the burden of obesity and thus optimise the benefits of these therapeutic strategies.

A second key finding highlights the magnitude of benefits that accrue from successful therapeutic intervention targeting high blood pressure, hypercholesterolaemia and hyperglycaemia even among individuals who are overweight or obese, reducing the excess risk of CHD by ∼50% and of stroke by ∼75%. These findings may provide further support for a ‘polypill’ of established inexpensive treatments targeting all three mediators to optimise adherence and thus potential benefit, particularly in lower-income regions with limited healthcare budgets.(3,4) However, it is also evident that the association between adiposity and cardiovascular disease is not completely explained by these three mediators. Even with optimal management of blood pressure, blood glucose and cholesterol, a substantial residual cardiovascular risk persists. This residual risk undoubtedly relates to both recognised and emerging risk factors, as highlighted in the most recent definition proposed by the Residual Risk Reduction Initiative (R3i). In this definition, residual vascular risk, i.e. of micro- and macro-vascular events, encompasses both the risk from established risk factors (such as unhealthy lifestyles, dyslipidaemia, high blood pressure, high blood sugar and obesity) and emerging risk factors that persist despite current evidence-based medical care. Consequently, these data not only provide a strong rationale for optimising the management of recognised modifiable risk factors, but also highlight the need for research aimed at identifying other potential contributors, including those mediated by inflammatory and thrombogenic pathways. Both components are consistent with the mission of the R3i.

This analysis has a number of important strengths. First, it represents the largest pooled analysis of multiple cardiovascular disease risk factors, including data from 1.8 million subjects. Second, the analysis included both Western and Asian cohorts, which enabled analysis of the impact of BMI in different ethnicities. The fact that the study showed consistent findings irrespective of the ethnicity of the cohort provides a clear rationale for sustained approaches targeting weight reduction and potential treatment gaps in the implementation of guideline-recommended therapeutic strategies. To ensure the long-term success of such approaches clearly requires vested commitment at the public policy level.