Cardiovascular risk factors over the life course

Cardiovascular disease (CVD) usually manifests itself at middle age or beyond, but it is the result of an ongoing disease process. This stresses the need for insight into changes in lifestyle and metabolic risk factors that occur throughout the life course, and their effect on CVD. We studied risk factors across generations, and observed that younger generations had a higher age-specific prevalence of hypertension, overweight and obesity than 10-year older generations. We concluded that in particular the prevalence of obesity and the lifelong exposure to obesity is increasing in younger generations. In all generations, individuals with a stable body mass index had no or slightly increasing levels of markers of oxidative stress and chronic inflammation during follow-up, while individuals with increasing body mass index had increases that were 2-4 times larger.These findings underscore the importance of maintaining a healthy weight throughout the life courseto improve population levels of oxidative stress and chronic inflammation. Subsequently, we studied the associations between risk factor profiles and the occurrence of cardiovascular diseases. Maintaining a healthy lifestyle profile (four or five healthy lifestyle factors: non-smoking, a healthy diet, adequate physical activity, moderate alcohol consumption and a healthy body mass index) was associated with a 2.5 times lower risks of CVD compared with maintaining only 0-1 healthy lifestyle factor. Independent of the lifestyle profile at young adulthood/middle age, each healthy lifestyle factor ‘lost’ over a five-year period was associated with a one-third higher risk of CVD and all-cause mortality, whereas improvement in lifestyle over the same period did not significantly reduce those risks. We further showed that only 7% of the participants maintained a low metabolic risk profile (i.e. ideal levels of blood pressure, cholesterol and body mass index, non-smoking and no diabetes) over 11 years. Participants who maintained a low metabolic risk profile had a 7 times lower risk of CVD than participants who maintained a high metabolic risk profile, whereas those with a low metabolic risk profile at baseline whose profile deteriorated over time had only a 3 times lower risk of CVD. We concluded that 40% and 86% of all CVD cases were attributable to suboptimal lifestyle profiles and metabolic risk profiles respectively. Finally, we studied trajectories of metabolic risk factors and biochemical markers preceding cardiovascular disease and type 2 diabetes. We showed that differences in metabolic risk factors and biochemical markers between cases and controls were already present 15-20 years before diagnosis of CVD. These differences remained constant over time. In contrast, for type 2 diabetes, levels of metabolic risk factors and biochemical markers deteriorated more rapidly in cases than in controls over the 15-20 years before diagnosis. Therefore, prevention of CVD and type 2 diabetes would require different strategies to be optimally effective. Overall, the findings of this thesis underscore the importance of not only focussing CVD prevention in high risk groups, but also at increasing the currently low proportion of adults with long-term healthy lifestyles and favourable levels of metabolic risk factors to minimalize the burden of CVD.