Brain-type natriuretic peptide is a useful biomarker of cardiovascular disease and predictor of cardiac-related mortality in chimpanzees (Pan troglodytes)

Figures

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  Figure 1—. The goal of this study was to validate the use of brain-type natriuretic peptide (BNP) for detecting and monitoring cardiac dysfunction in captive chimpanzees (Pan troglodytes). We analyzed cross-sectional (N = 175) and longitudinal (N = 76) BNP, echocardiogram, ECG, and pathology data from living and deceased captive chimpanzees to examine age and sex effects and to assess the usefulness of BNP for detecting cardiovascular disease and predicting mortality. The study period was from July 2010 through October 2024. Different statistical analyses required different subgroupings of chimpanzees. This figure shows the demographic breakdown and criteria for inclusion for each subgroup.

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  Figure 2—. Cross-sectional analysis: among the sample of 175 chimpanzees described in Figure 1, a Mann-Whitney U test for the overall sample comparing BNP values in living (N = 101; mean, 59.44; mean rank, 72.43; median, 44.80; quartile 1 (Q1), 25.00; Q3, 73.70) and deceased (N = 74; mean, 179.21; mean rank, 109.26; median, 85.55; Q1, 42.10; Q3, 179.00) chimpanzees was significant (P < .001). This was also the case within female (P = .001) and male (P < .001) cohorts. As can be seen in (A), for both males and females, deceased chimpanzees had higher BNP values than those that were still living as of October 2024. Longitudinal analyses: Within the full sample of 175 chimpanzees, there were 76 chimpanzees (41 alive, 35 deceased) that had BNP data points that were separated by at least 3 years. We computed BNP difference scores for time points 1 and 2 for the BNP values (thus, higher BNP difference scores reflect an increase over time). Mann-Whitney U tests revealed significant differences in BNP difference scores between the living and deceased individuals for the entire sample (P = .001), with deceased chimpanzees having higher BNP difference scores than those still living. Separate analyses…

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  Figure 3—. Among the sample of chimpanzees described in Figure 1, there are 75 chimpanzees (41 females, 34 males) that died by October 2024. For these 75 deceased subjects, Kaplan-Meier survival analysis showing time (in number of days) between initial BNP data points and death for 2 groups: those with an initial BNP value < 100 pg/mL (N = 42, blue solid line) and those with an initial BNP value > 100 pg/mL (N = 33, green dotted line). The graph includes 95% CIs. A steeper slope (ie, BNP > 100 pg/mL) indicates a higher event rate (death rate) and therefore a worse survival prognosis. A less steep slope (ie, BNP < 100 pg/mL) indicates a lower event rate and therefore a better survival prognosis. A comparison of these survival curves (log-rank test) revealed significant differences in survival between the 2 groups (χ2 = 4.5953; degrees of freedom, 1; P = .0321).

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  Figure 4—. Among the sample of chimpanzees described in Figure 1, there are 91 subjects (50 living, 41 deceased) for whom a cardiac score was assigned the same day a sample was taken for BNP analysis. Thus, we were able to associate cardiac scores with BNP values for these subjects to assess whether BNP values significantly differed between cardiac scores. A Kruskal-Wallis test revealed significant differences in BNP values between cardiac score categories (P < .001). Chimpanzees with a cardiac score of B (N = 36; mean, 132.57; mean rank, 54.61) or C (N = 7; mean, 172.60; mean rank, 71.86) exhibited higher BNP values, on average, than chimpanzees with a cardiac score of A (N = 48; mean, 68.58; mean rank, 35.77). In our sample, no chimpanzees received cardiac score D in association with a BNP sample. This figure shows mean rank BNP values between cardiac scores—the solid lines in the boxes depict median values, the top and bottom of the box depict upper and lower quartile values, and the whiskers depict maximum and minimum data values. *Significance at P < .05. ns = Not significant.

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  Figure 5—. A χ2 test of independence was used to assess if, among a sample of 50 deceased chimpanzees with known causes of death (described in Figure 1), those with initial BNP values > 100 pg/mL were more likely to have cardiac factors listed as their proximate cause of death than those with initial BNP values < 100 pg/mL. Here, the number of years between initial BNP and death ranged from 0.00 to 13.57 years (mean, 5.32 years; SE, 0.41), and the goal of this analysis was to test whether early BNP values predicted subsequent cardiac death. The χ2 test was statistically significant (χ2 = 10.588; N = 50; P = .001). Chimpanzees that had an initial BNP value > 100 pg/mL were significantly more likely to have cardiac factors listed as their proximate cause of death than those that had initial BNP scores < 100 pg/mL. Indeed, 17 of 21 chimpanzees that apparently died from heart-related causes (81%; depicted by the black bars on the graph) had an initial BNP value > 100 pg/mL.