Publications

BACKGROUND

Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts mortality in patients with chronic stable angina or acute coronary syndrome. However, the association of GDF-15 with cardiovascular (CV) events and the mechanisms of this association are not well understood.

METHODS

We measured plasma GDF-15 and cardiac disease severity in 984 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent CV events (myocardial infarction, stroke, and CV death), hospitalization for heart failure, and all-cause mortality were determined by chart review during an average of 8.9-year follow-up.

RESULTS

Each doubling in GDF-15 was associated with a 2.5-fold increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001). This association persisted after extensive adjustment for covariates including comorbid conditions, measures of cardiac disease severity, cardiac function, inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01). Participants who had GDF-15 levels in the highest tertile had higher mortality compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P ≤ .001 adjusted for all covariates). Addition of GDF-15 to existing risk factors resulted in a 50% change in net reclassification of patients' risk for mortality.

CONCLUSIONS

Higher levels of GDF-15 are associated with major CV events in patients with stable ischemic heart disease. This suggests that GDF-15 is capturing an element of risk not explained by other known risk factors.

The pathology of pulmonary hypertension includes numerous abnormalities of the intima, media, and adventitia of the pulmonary vascular tree. A recently completed systematic analysis revealed high variability of morphologic measurements within a given pulmonary arterial hypertension (PAH) lung and among all PAH lungs, as well as distinct pathologic subphenotypes, and included a subset of lungs lacking intimal and medial remodeling. There was correlation between perivascular inflammation, remodeling, and hemodynamics. This article summarizes the pathologic features of the normal and abnormal pulmonary circulation, and correlations with animal models.