Metabolic Syndrome and Cardiovascular Disease -3

To reduce the burden of metabolic syndrome in society, obesity prevention deserves a high priority for public health. This is true for all nations of the world.
Changing lifestyles can largely account for the rising prevalence of the syndrome throughout the world. For much of the world, life is becoming more sedentary and food is increasingly available.  Both lead to energy overload and obesity.

Society is ill prepared to reverse this trend. But both governments and society at large must recognize the consequences of allowing obesity to develop unchecked.
Greater national commitments to modifying the structure of daily life habits will be required to reverse this unfortunate trend.

For individuals who have developed obesity,  management requires intervention by the healthcare community. Priority in clinical management should go to persons in whom obesity has elicited the metabolic syndrome. A major challenge to the healthcare system is to develop more efficient lifestyle interventions.

This may require creation of clinical management structures that do not currently exist in most medical settings. In overweight/obese subjects with the metabolic syndrome, the primary goal is to reduce body weight by 10% in the first year. If this can be achieved, a secondary goal is to reduce weight to the desirable range, e.g., a body mass index less than 25 kg/m 2 . To achieve these goals, a combination of caloric restriction, behavior modification, and increased physical activity will be required.

The second aim in management of the metabolic syndrome is to reduce metabolic susceptibility. The most practical means for achieving this aim is to enhance physical activity.  Regular exercise will lower insulin resistance, improve cardiovascular risk factors overall, and reduce risk for cardiovascular events through multiple mechanisms.  Further any secondary causes of metabolic susceptibility should be appropriately treated.  Drug treatment of metabolic susceptibility is problematic.  However,  insulin sensitizers are promising. Included in this list are metformin and thiazolidinediones. The pharmaceutical industry is engaged in intensive research to develop new agents for reducing susceptibility to the metabolic syndrome; but at present, this field of research is in its infancy.

The third therapeutic approach is to favorably modify each of the risk-factor components of the syndrome with drug therapies. It is appropriate to use absolute risk estimates to guide choice and intensity of drug therapy.  Several risk-assessment tools are available for estimating absolute risk.  Among these are Framingham and PROCAM risk scoring.  Others are under development.

Eventually, population-based risk scoring will be available so that absolute risk can be estimated from equations that factor in the baseline risk of the population.

Some investigators have attempted to estimate absolute risk from the components of the metabolic syndrome alone. This is a mistake. The components of the syndrome do not incorporate all of the contributions to global cardiovascular risk.

Recently, the American Diabetes Association has introduced a multiple-component risk algorithm called Archimedes. This algorithm estimates what is called cardiometabolic risk . This term can be taken to refer to all cardiovascular diseases of atherosclerotic origin plus all other diseases of metabolic origin.  Among the metabolic diseases are prediabetes, diabetes, fatty liver, cholesterol gallstones, polycystic ovarian syndrome,  and obstructive sleep apnea.  The current Archimedes algorithm includes multiple risk factors but at present only predicts absolute risk for cardiovascular disease and diabetes. Presumably as it is developed it will extend to predict other metabolic diseases.  This ambitious program currently is a work in progress, and it will have to be validated with a variety of databases.

First-line therapy for atherogenic dyslipidemia is to reduce apolipoprotein B levels.  Statin drugs are the most effective apolipoprotein B-lowering drugs.
Other drugs that lower apolipoprotein B levels in patients with elevated triglycerides are ezetimibe,  fibric acids,  and nicotinic acid.  The latter two also raise high-density lipoprotein-cholesterol levels,  which may provide additional risk reduction. Currently, other drugs are under development that raise high-density lipoprotein concentrations. Whether these drugs produce incremental risk reduction awaits on-going clinical trials.

The primary target of vascular dysfunction is an elevated blood pressure. Many investigators favor use of drugs that dampen the renin-angiotensin system in patients with the metabolic syndrome. This is particularly the case for those patients who have Type 2 diabetes. Calcium-channel blockers are effective blood-pressure lowering agents,  and generally are devoid of metabolic side effects.

Beta-blockers and diuretics both can worsen insulin resistance,  but may be required to achieve blood pressure goals in some patients.

The major unresolved question about glucose elevations in the prediabetes range is whether glucose-lowering drugs are indicated to prevent progressive hyperglycemia.  Without doubt clinical hyperglycemia is a risk factor for both macrovascular and microvascular diseases. But is it enough just to treat hyperglycemia when it reaches the level of Type 2 diabetes? Ongoing clinical trials are discussing this question.

At present, there are no specific therapies for a prothromobotic state other than antiplatelet drugs, notably, aspirin. If patients with the metabolic syndrome have reached a level of risk high enough, the benefits of aspirin therapy outweigh the potential side effects- particularly bleeding complications. Further, there is currently no specific treatment for a proinflammatory state other than a reduction through lifestyle changes.

In summary, the metabolic syndrome as a multiplex cardiovascular risk factor is growing in importance as the world’s population becomes increasingly sedentary and overweight. First and foremost, this is a public health problem.

But the medical community has an important role to play in the management of the metabolic syndrome as a risk factor, just as they do for single risk factors such as smoking, hypertension, and hypercholesterolemia. Metabolic Syndrome and Cardiovascular Disease will help provide healthcare providers,  researchers, and educators with the tools necessary to help combat this important problem on a global scale.


Scott M. Grundy, MD, PhD
Professor of Internal Medicine
Distinguished Chair in Human Nutrition
Director, Center for Human Nutrition
University of Texas, Southwestern Medical Center
Dallas, Texas, U.S.A.

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