UK Biobank: opportunities for cardiovascular research.

TLDR: It is demonstrated conclusively that a continuous increase in blood pressure corresponds with an increased risk of vascular death across all age groups, and the importance of a large sample size (about 500 000 participants) for detecting this association is illustrated.

Abstract: Cardiovascular diseases are a major cause of morbidity and mortality, accounting for 45% of all deaths in European countries in 20161 and almost a third of deaths worldwide in 2013.2 A similar pattern is observed in the UK where cardiovascular diseases were responsible for 27% of deaths in 2014, with coronary heart disease resulting in the largest number of deaths attributable to a single cause (n = ∼69 000) whilst stroke is the third biggest cause (n = ∼39 000).3 Although age-standardized cardiovascular disease mortality rates are decreasing worldwide, the total deaths and burden as measured through disability-adjusted life years of cardiovascular diseases are increasing.4,5 Furthermore, in the UK, cardiovascular risk factors such as high blood pressure and high cholesterol are among the leading causes of disease burden.6 Epidemiological studies have historically played an essential role in identifying the causes and consequences of cardiovascular disease and have resulted in improvements in prevention and treatment. The seminal US-based Framingham Heart Study which recruited 5200 participants between 1948 and 1952, was integral in identifying a range of important risk factors for cardiovascular disease, such as high blood pressure, a high cholesterol level, cigarette smoking, obesity and physical inactivity, and consequently shifted the focus from management to preventative strategies for cardiovascular disease.7 This, together with findings from other epidemiological studies, such as the Seven Countries Study and the MONICA project,8 have been influential in leading to treatments for the primary and secondary prevention of cardiovascular events, most notably statins (that act to lower cholesterol levels), and anithypertensives.9,10 Epidemiological studies such as the Framingham Heart Study with moderate sample sizes are useful in detecting risk factors with large effects on common outcomes; however, they lack statistical power to reliably identify risk factors which have small to moderate effects or to assess associations with disease across subgroups of the population. The need for large sample sizes has led to collaborative efforts, such as the Prospective Studies Collaboration (an individual participant meta-analysis of data from 61 studies and more than a million participants11) that has demonstrated conclusively that a continuous increase in blood pressure corresponds with an increased risk of vascular death across all age groups (see Figure ​Figure11 that illustrates the importance of a large sample size (about 500 000 participants) for detecting this association).12 Sample size is also of particular importance in the current era of genome-wide association studies, where many investigations are aiming to detect either small effects from common variants or large effects from rare variants.13 Open in a separate window Figure 1 Absolute risk of ischaemic heart disease mortality by usual systolic blood pressure and age at risk in 5000, 50 000, and 500 000 participants. Unpublished figure containing data from the Prospective Studies Collaboration, obtained through personal communication. CI, confidence interval; IHD, ischaemic heart disease.