High-Sensitivity Troponin T and I Among Pregnant Women in the US—The National Health and Nutrition Examination Survey, 1999-2004

Abstract

This cross-sectional study investigates the expected physiologic concentrations of high-sensitivity cardiac troponin in normal pregnancy.

Pregnancy is associated with major physiologic cardiovascular changes, including weight gain and increased heart rate and plasma volume.¹ These changes result in dynamic alterations in the cardiac biomarker N-terminal pro–brain natriuretic peptide (NT-proBNP), which has been shown to decrease substantially over the course of pregnancy.² High-sensitivity cardiac troponin (hs-cTn) is an important cardiac biomarker used to define myocardial injury and has utility for initial evaluation for possible cardiac disease and for risk stratification in the general population. Cardiovascular disease is the leading cause of nonobstetric mortality and morbidity in pregnancy in the US.³ However, the expected physiologic hs-cTn concentrations in normal pregnancy are uncharacterized.⁴

Methods

We measured troponin levels in stored samples and conducted a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004.⁵ We included women (self-reported biologic sex) aged 18 to 40 years (a portion of whom were pregnant) without a history of cardiovascular disease. Levels of hs-cTn T were measured using the Gen 5 STAT assay (Roche Diagnostics). Levels of hs-cTn I were measured using 3 different assays: Abbott Laboratories, Siemens Healthcare Diagnostics, and Ortho Clinical Diagnostics VITROS.⁶ Written informed consent was obtained per NHANES protocol, and the ethics board of the National Center for Health Statistics approved this stored serum study. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed.

We compared the distributions of hs-cTn level in nonpregnant and pregnant women and used logistic regression to evaluate the associations of pregnancy status and cardiovascular risk factors with elevated hs-cTn T level, defined as greater than or equal to 3.8 ng/L (≥75th percentile among nonpregnant women; to convert to micrograms per liter, divide by 1000). All analyses accounted for the complex survey design and were weighted to generate nationally representative estimates.

Results

Among 2358 women, 622 were pregnant. Overall, 13% identified as non-Hispanic Black, 9% as Mexican American, 65% as non-Hispanic White, and 12% as other racial and ethnic groups. For both nonpregnant and pregnant women, less than 5% had diabetes (self-report or hemoglobin A_1c >6.5%), and less than 10% had high blood pressure (self-report or blood pressure >120/80 mm Hg).

The distributions of hs-cTn values in nonpregnant and pregnant women (overall and within trimesters) were similar across all 4 hs-cTn assays (Figure). Associations of elevated troponin with demographic and cardiovascular risk factors were similar after adjustment for advanced maternal age (≥35 years), race and ethnicity, diabetes or prediabetes, systolic blood pressure, and estimated glomerular filtration rate for both hs-cTn I and T level (Table).

Figure. Distribution of High-Sensitivity Cardiac Troponin (hs-cTn) Among Nonpregnant and Pregnant Women by Trimester, Aged 20 to 40 Years, National Health and Nutrition Examination Survey (NHANES), 1999-2004.

Cardiac troponin distribution of nonpregnant and pregnant women aged 20 to 40 years from the NHANES. The following assays were performed: hs-cTn T (Roche) (A); hs-cTn I (Abbott) (B); hs-cTn I (Siemens) (C); and hs-cTn I (Ortho) (D).

Table. Characteristics of the Population and Adjusted Associations of Cardiovascular Risk Factors With Elevated High-Sensitivity Cardiac Troponin (hs-cTn) T and I by Pregnancy Status Among US Women Aged 20 to 40 Years.

Characteristica	Nonpregnant women (unweighted n = 1736)	Pregnant women (unweighted n = 548), trimester
		1st (unweighted n = 105)	2nd (unweighted n = 234)	3rd (unweighted n = 209)
Age, mean (SE), y	30.2 (0.2)	28.6 (0.8)	26.8 (0.7)	28.7 (0.6)
Race and ethnicity, mean (SE), %
Non-Hispanic Black	13.0 (1.2)	5.0 (2.2)	16.0 (4.5)	14.8 (5.2)
Mexican American	9.0 (1.1)	16.5 (4.8)	13.5 (2.8)	10.8 (2.8)
Non-Hispanic White	66.3 (2.0)	68.5 (8.5)	60.4 (5.8)	49.3 (7.1)
Other race and ethnicityb	11.7 (1.7)	10.0 (6.5)	10.1 (3.2)	25.1 (6.8)
Prediabetes or diabetes, mean (SD), %	30.0 (1.5)	49.4 (10.0)	32.9 (5.1)	42.7 (6.0)
Systolic BP, mean (SE), mm Hg	110.4 (0.4)	107.1 (2.0)	105.6 (1.4)	109.5 (1.1)
eGFR, per 10 mL/min/1.73m2, median (IQR)	118.3 (109.2-125.7)	134.1 (126.1-138.7)	136.8 (129.2-144.1)	124.0 (107.1-131.0)
Adjusted associations a	hs-cTn Tc Nonpregnant women	hs-cTn Tc Pregnant women	hs-cTn I d Nonpregnant women	hs-cTn I d Pregnant women
Advanced maternal age (>35 vs <35 y), OR (95% CI)	1.09 (0.82-1.44)	1.03 (0.40-2.69)	1.01 (0.77-1.33)	2.08 (0.77-5.58)
Race and ethnicity, OR (95% CI)
Non-Hispanic Black	0.90 (0.59-1.37)	0.47 (0.16-1.33)	1.37 (0.93-2.01)	1.54 (0.82-2.87)
Mexican American	1.10 (0.68-1.76)	1.89 (0.85-4.17)	0.75 (0.53-1.08)	1.09 (0.50-2.41)
Non-Hispanic White	1 [Reference]	1 [Reference]	1 [Reference]	1 [Reference]
Other race and ethnicityb	1.12 (0.68-1.84)	0.33 (0.06-1.70)	1.06 (0.62-1.80)	0.87 (0.29-2.64)
Prediabetes or diabetes (vs none), OR (95% CI)	1.41 (0.96-2.09)	1.70 (0.39-7.42)	1.05 (0.67-1.63)	1.60 (0.44-5.81)
Systolic BP, per 10 mm Hg, OR (95% CI)	1.22 (1.08-1.38)	1.46 (1.02-2.08)	1.34 (1.20-1.50)	1.82 (1.15-2.87)
eGFR, per 10 mL/min/1.73 m2, OR (95% CI)	0.78 (0.69-0.90)	0.61 (0.50-0.75)	0.84 (0.76-0.93)	0.68 (0.54-0.86)

Abbreviations: BP, blood pressure; eGFR, estimated glomerular filtration rate.

SI conversion factor: To convert hs-cTn to micrograms per liter, divide by 1000.

^a Demographic data shown for pregnant women with known trimester status. Adjusted associations performed using larger sample size for pregnant women.

^b Other race and ethnicity includes Alaska Native, Asian Indian, Chinese, Filipino, Guamanian, Indian (American), Japanese, Korean, Native Hawaiian, Samoan, Vietnamese, other Asian, other Pacific Islander, and other race.

^c Elevated hs-cTn T was defined as 3.8 ng/L or greater (>75th percentile among nonpregnant women).

^d Results shown using the Abbott hs-cTn I assay.

Discussion

In a representative sample of US adult women aged 20 to 40 years without existing cardiovascular disease, we provided data on the expected physiologic hs-cTn values during pregnancy. Results suggest that hs-cTn levels were comparable among pregnant and nonpregnant women across all trimesters and across 4 different assays. Pregnant women did not have elevated hs-cTn levels compared with nonpregnant women, before or after adjustment for demographic and clinical factors, suggesting that pregnancy alone does not result in significant changes in troponin levels.

The notable strength of this study is the large, diverse sample drawn from the general US adult population, as well as the examination of multiple troponin assays. The major limitation of this study is a lack of longitudinal data on women over time, and postpartum values may differ. However, the similar findings between nonpregnant and pregnant women in all trimesters strongly suggest that hs-cTn level remains stable throughout pregnancy.

Overall, these findings suggest that hs-cTn level remains stable over pregnancy, and correlates of hs-cTn level are similar in pregnant and nonpregnant women. hs-cTn levels can be interpreted similarly in pregnant and nonpregnant women when evaluating for cardiovascular disease and do not appear to be associated with weight gain and hemodynamic changes during pregnancy when compared with other cardiac biomarkers, such as NT-proBNP.

Supplement.

Data Sharing Statement