Metabolic Syndrome and Cardiovascular Disease -2

Third, the metabolic syndrome is accompanied by increases in acute phase proteins, such as C-reactive protein. Several reports suggest that these proteins may have proatherogenic properties. And finally, there is a cellular inflammatory response in the arterial way secondary to interaction with the known metabolic risk factors; this inflammatory response may be heightened by increases in circulating inflammatory cytokines.

As indicated above, each of the components of the metabolic syndrome hasbeen implicated in atherogenesis. Because of their colinearity within the syndrome, it has been difficult to dissect the relative contributions of each to atherosclerotic cardiovascular disease events. For this reason, the metabolic syndrome can be considered to be a multiplex cardiovascular risk factor. The metabolic syndrome belongs in the category of causative risk factors similar to individual risk factors of cigarette smoking, hypercholesterolemia, and hypertension.

The introduction of a multiplex risk factor is something new to the cardiovascular field, and not surprisingly, the understanding of the place of the metabolic syndrome in cardiovascular risk has been slow in development.

The question has arisen whether the risk for metabolic syndrome as a whole is greater than the sum of the risk factors of its individual components. This is a complex question, but can be addressed in several ways. First, epidemiological studies suggest that multiple risk factors are synergistic in raising risk and not just additive. This synergism has long been called multiplicative risk . Second, several of the risk components, e.g., elevated apolipoprotein B, a prothrombotic state, and a proinflammatory state, are not usually measured in clinical practice.

Consequently, their contribution to risk is not identified with the typical clinical measures. Third, some of the measured risk factors, such as low high-density lipoprotein cholesterol, may be predictive but not necessarily causative; thus, the individual risk factors that are used for prediction may be only markers for the true causative factors accompanying the syndrome. And fourth, the metabolic syndrome is a progressive disorder, that is, it worsens over time. Consequently, risk measured at any one time underestimates the long-term risk accompanying the syndrome.

Considerable confusion has arisen regarding the relation of the component metabolic risk factors to the risk surrogates (categorical risk markers) for these factors that are the basis for clinical diagnosis. In both updated Adult Treatment Panel III and International Diabetes Federation formulations of the risk the following surrogates are included:

• Serum triglycerides <150 mg/dL (<1.7 mmol/L)
• High-density lipoprotein cholesterol < 40 mg/dL (<1.0 mmol/L) in men, and <50 mg/dL (<1.3 mmol/L) in women
• Blood pressure <130 mmHg systolic, and <85 mmHg diastolic