The appetite physicians have for biomarkers that are predictive of risk for cardiovascular disease appears never to be satisfied. Ioannidis and Tzoulaki recently reviewed the literature on 10 popular “new” biomarkers and found that each one had accrued more than 6000 publications.1 The predictive effects of these popular blood biomarkers for coronary heart disease in the general population are listed in the Table.
|Biomarker||Adjusted Relative Risk (95% Confidence Interval)|
|C-reactive protein||1.39 (1.32–1.47)|
|Interleukin 6||1.27 (1.19–1.35)|
|BNP or NT-proBNP||1.42 (1.24–1.63)|
|Serum albumin||1.2 (1.1–1.3)|
|Uric acid||1.09 (1.03–1.16)|
The authors state that “Given that the majority of the predictive effects for these popular biomarkers are either null or small, their ability to improve reclassification of patients into more appropriate categories of risk is also expected to be infinitesimal.” This, of course, refers to the use of biomarkers in a large population.
On the contrary, biomarkers may be useful for identifying disease phenotypes. For example, an elevated homocysteine level might be of great importance to a young person with a myocardial infarction and a positive family history of similar occurrences. Emerging biomarkers, eg, asymmetric and symmetric dimethylarginine and galectin-3, are pointing the way to specific pathophysiologies for cardiovascular disease.
The definition of a biomarker used by the National Institutes of Health is “A characteristic that is objectively measured and evaluated as an indicator of normal biologic or pathogenic processes or pharmacological responses to a therapeutic intervention.” In this context, blood pressure remains the biomarker par excellence for hypertension and for many other cardiovascular entities.
The importance of blood pressure was highlighted by the report of the cardiovascular lifetime risk pooling project.2 The investigators examined how changes in blood pressure during middle age affected lifetime risk for cardiovascular disease, coronary heart disease, and stroke. Starting at 55 years of age, 61,585 men and women were followed over an average of 14 years, ie, 700,000 person-years. Individuals who maintained or decreased their blood pressure to normal levels had the lowest remaining lifetime risk for cardiovascular disease (22–41%) compared with individuals who had or developed hypertension by 55 years of age (42–69%), suggesting a dose-response effect for the length of time at high blood pressure levels. The investigators concluded that individuals who experience increases or decreases in blood pressure in middle age have associated higher and lower remaining lifetime risk for cardiovascular disease and efforts should continue to emphasize the importance of lowering blood pressure and avoiding or delaying the incidence of hypertension to reduce the lifetime risk for cardiovascular disease.
Yet, research into the recording and analysis of the blood pressure signal lags behind many other less significant biomarkers. It is time to harness the efforts of modern technology to develop more advanced application of this marvelous clinical indicator. As for hypertension, we must not be satisfied until we can detect and interrupt the disease prior to blood pressure elevation.