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Cholecystokinin in plasma predicts cardiovascular mortality in elderly females
Jens P Goetze1, Jens F Rehfeld2, Urban Alehagen3
1Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Insights
Plasma cholecystokinin (CCK) levels predict cardiovascular mortality in elderly women. This finding introduces gender-specific risk assessment using CCK measurements.
Area of Science:
- Endocrinology
- Cardiology
- Geriatrics
Background:
- Gastrointestinal hormones cholecystokinin (CCK) and gastrin have known cardiovascular effects.
- The predictive value of endogenous CCK and gastrin for cardiovascular mortality is not established.
Purpose of the Study:
- To investigate whether plasma levels of CCK and gastrin can predict cardiovascular mortality in elderly patients.
- To explore gender-specific differences in the association between CCK, gastrin, and cardiovascular mortality.
Main Methods:
- A 13-year prospective study of 470 elderly primary care patients with cardiac symptoms.
- Cox proportional hazard regression and Kaplan-Meier analyses were used to evaluate 5-year all-cause and cardiovascular mortality.
- Statistical models included established cardiovascular risk factors and NT-proBNP concentrations.
Main Results:
- Elevated plasma CCK concentrations (4th quartile) were significantly associated with increased 5-year cardiovascular mortality in univariate and multivariate analyses.
- This association remained significant even after adjusting for NT-proBNP.
- A markedly higher risk was observed in female patients (HR 8.99) compared to male patients (HR 1.47).
Conclusions:
- Plasma CCK is an independent predictor of cardiovascular mortality in elderly women.
- Plasma CCK measurement can enhance gender-specific cardiovascular risk assessment.
Background:
Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality.
Methods:
Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point.
Results:
In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p<0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p=0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p=0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p=0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk.
Conclusions:
CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment.
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