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Inflammation, Cholesterol, Lp(a) Levels, and 30-Year Cardiovascular Outcomes in Women
TAKE-HOME MESSAGE
- In this prospective cohort study involving 27,939 healthy women, baseline levels of high-sensitivity C-reactive protein, LDL-C, and lipoprotein(a) significantly and independently predicted the 30-year risk of incident major cardiovascular events. Models incorporating all three biomarkers conferred the widest spread for risk across the population.
- These findings underscore the diverse pathobiological pathways contributing to atherosclerotic events and highlight the need to transition from narrow 10-year perspectives to life-course approaches for the prevention of cardiovascular disease.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
High-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year and 10-year predictions of cardiovascular risk and represent distinct pathways for pharmacologic intervention. More information about the usefulness of these biomarkers for predicting cardiovascular risk over longer periods of time in women is needed because early-life intervention represents an important risk-reduction method.
METHODS
We measured high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in 27,939 initially healthy U.S. women who were subsequently followed for 30 years. The primary end point was a first major adverse cardiovascular event, which was a composite of myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes. We calculated the adjusted hazard ratios and 95% confidence intervals across quintiles of each biomarker, along with 30-year cumulative incidence curves adjusted for age and competing risks.
RESULTS
The mean age of the participants at baseline was 54.7 years. During the 30-year follow-up, 3662 first major cardiovascular events occurred. Quintiles of increasing baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) all predicted 30-year risks. Covariable-adjusted hazard ratios for the primary end point in a comparison of the top with the bottom quintile were 1.70 (95% confidence interval [CI], 1.52 to 1.90) for high-sensitivity CRP, 1.36 (95% CI, 1.23 to 1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21 to 1.47) for lipoprotein(a). Findings for coronary heart disease and stroke appeared to be consistent with those for the primary end point. Each biomarker showed independent contributions to overall risk. The greatest spread for risk was obtained in models that incorporated all three biomarkers.
CONCLUSIONS
A single combined measure of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels among initially healthy U.S. women was predictive of incident cardiovascular events during a 30-year period. These data support efforts to extend strategies for the primary prevention of atherosclerotic events beyond traditional 10-year estimates of risk.
Additional Info
Disclosure statements are available on the authors' profiles:
Modifiable blood biomarkers such as hsCRP, LDL-C, and Lp(a) can be instrumental for understanding biology, predicting risk, and targeting cardiovascular interventions. However, data are scarce on the long term (25- to 30-year) risks associated with these biomarkers when used alone and in combination, particularly among women for whom cardiovascular disease remains under-diagnosed and under-treated.
My colleagues and I hypothesized that a single baseline measure of hsCRP, LDL-C, and Lp(a) obtained in mid-life could predict future cardiovascular risk in women over a 30-year period. We addressed these issues in the NIH-funded Women’s Health Study (WHS), a prospective cohort of 27,939 initially healthy American women who had all three biomarkers measured in a blood sample obtained at baseline and who have been followed for over a 30-year period for major cardiovascular events.
Our results are striking. First, low grade systemic inflammation detected by hsCRP was a stronger predictor of future cardiovascular events over the next 30 years than either LDL-C or Lp(a), yet in clinical practice hsCRP is the least likely biomarker to be measured by most clinicians. These data should challenge internists to learn more about inflammation biology, particularly as low-dose colchicine has now been approved by the US FDA as the first targeted anti-inflammatory drug to prevent atherosclerotic events.
Second, hsCRP, LDL-C, and Lp(a) are independent of each other and tell us that different biologic processes are at play for individual patients; we therefore should be targeting preventive efforts at the biologic issue our individual patient suffers from and not assume one size fits all. Some women will be affected by more than one of these abnormal pathways – when used in combination, those who had elevated levels of all three biomarkers had a threefold elevation of risk, even when only 40 years old.
Last, we need to move well past 5-year or 10-year risk predictions. If one calculates cardiovascular risk in the manner suggested by current guidelines, very few women will be identified as being at high risk until they are well into their 60s if not 70s, too late for real prevention. A new way to address prevention is needed, and a simple one-time screen early in life for hsCRP, LDL-C, and Lp(a) will get us a long way toward that goal.
The bottom line is that doctors cannot treat what they do not measure, and prevention cannot wait until advance disease is present.