Stevo Julius
University of Michigan Medical Center, Ann Arbor, MI, USA

Many decades ago, the Framingham Study reported that a combination of high blood pressure (BP) with another risk factor greatly increases an individual’s cardiovascular (CV) risk. Risk calculation tables became popular and doctors used them to explain to patients their odds of suffering a CV event in the future. These tools could have helped foster disease prevention, but they unintentionally conveyed the wrong message. Framingham investigators realised that these risk factors were strongly interrelated. However, the risk tables gave each laboratory result on a separate line and created the perception that risk factors are independent of one another. In parallel, the research community also failed to focus on the commonality of risk factors. Components of the syndrome were pursued by lipidologists, diabetologists, nutritionists, or hypertensiologists. Recently, a consensus has evolved that the Metabolic Syndrome is a multifaceted but distinct entity, and that further progress depends in part on interdisciplinary dissemination of knowledge. The formation of the Metabolic Syndrome Institute, headquartered in France, accurately reflects this new consensus.

My interest in the Metabolic Syndrome stems from clinical trials and from my own laboratory. In population studies, there is a linear relationship of BP with stroke and coronary heart disease (CHD): the higher the BP, the greater the incidence of strokes and CHD. It was therefore expected that lowering BP would similarly reduce stroke and CHD, but a surprise was in the making. After decades of clinical research and in studies that involved hundreds of thousands of patient-years, it became clear that BP lowering reduces stroke more than CHD. This discrepancy is easily explained by calculations that about half of the risk of CHD in hypertension reflects the ubiquitous presence of Metabolic Syndrome in hypertension.

Some thirty years ago, the Metabolic Syndrome become so forcefully apparent to me that it was impossible to ignore. We investigated very early phases of hypertension – the so-called borderline hypertension. Since cardiac output and plasma volume are proportional to body weight, and our patients were 12 kg heavier than the controls, the raw values for the two groups could not be compared. Normalising the values to indexes of body size satisfied some journal referees but not others. Next we decided to weight-match the groups, but it took us three full years to find normotensive subjects of similar weight. Clearly, overweight was part of the syndrome of hypertension. In later studies, we repeatedly found that subjects with borderline hypertension also had dyslipidaemia, high plasma insulin levels, and abnormal waist-to-hip ratio. The close and early association of BP elevation with metabolic abnormalities suggests that these apparently diverse abnormalities might share a common pathophysiology. Having explained the background, let me now answer your question about the importance of the Metabolic Syndrome. The answer is simple. Clinically, the Metabolic Syndrome occurs rather early in a patient’s life, greatly increases his/her CV risk, and consists of multiple abnormalities. Consequently, the approach to treatment must be “holistic” and aim at ameliorating all facets of the syndrome. In terms of research, the Metabolic Syndrome is a promising field. Should proof be given that this condition has a common pathophysiology, it could open the doors to better, more specific therapy.