Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004.

BACKGROUND: Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mm Hg or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. METHODS: We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. We measured hs-cTnI (high-sensitivity cardiac troponin I), hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. RESULTS: Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. CONCLUSIONS: Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999-2004.

Objective: High sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). Methods: We studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. Results: Mean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). Conclusion: In US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.

A National Survey of Physicians' Views on the Importance and Implementation of Deintensifying Diabetes Medications.

BACKGROUND: Guidelines recommend deintensifying hypoglycemia-causing medications for older adults with diabetes whose hemoglobin A1c is below their individualized target, but this rarely occurs in practice. OBJECTIVE: To understand physicians' decision-making around deintensifying diabetes treatment. DESIGN: National physician survey. PARTICIPANTS: US physicians in general medicine, geriatrics, or endocrinology providing outpatient diabetes care. MAIN MEASURES: Physicians rated the importance of deintensifying diabetes medications for older adults with type 2 diabetes, and of switching medication classes, on 5-point Likert scales. They reported the frequency of these actions for their patients, and listed important barriers and facilitators. We evaluated the independent association between physicians' professional and practice characteristics and the importance of deintensifying and switching diabetes medications using multivariable ordered logistic regression models. KEY RESULTS: There were 445 eligible respondents (response rate 37.5%). The majority of physicians viewed deintensifying (80%) and switching (92%) diabetes medications as important or very important to the care of older adults. Despite this, one-third of physicians reported deintensifying diabetes medications rarely or never. While most physicians recognized multiple reasons to deintensify, two-thirds of physicians reported barriers of short-term hyperglycemia and patient reluctance to change medications or allow higher glucose levels. In multivariable models, geriatricians rated deintensification as more important compared to other specialties (p=0.027), and endocrinologists rated switching as more important compared to other specialties (p<0.006). Physicians with fewer years in practice rated higher importance of deintensification (p<0.001) and switching (p=0.003). CONCLUSIONS: While most US physicians viewed deintensifying and switching diabetes medications as important for the care of older adults, they deintensified infrequently. Physicians had ambivalence about the relative benefits and harms of deintensification and viewed it as a potential source of conflict with their patients. These factors likely contribute to clinical inertia, and studies focused on improving shared decision-making around deintensifying diabetes medications are needed.

Idiopathic Hypercalciuria - A Major Metabolic Risk for Calcium Kidney Stone Disease.

Idiopathic hypercalciuria is defined as excessive urine calcium excretion in the absence of an identifiable cause. It has been strongly associated with the risk of calcium kidney stone formation. Animal and human studies have suggested excessive bone mineral loss or increased gastrointestinal calcium absorption with abnormal renal calcium excretion may contribute to this process. In this article we will review the complex pathophysiology of idiopathic hypercalciuria and discuss clinical management and challenges.

Racial and ethnic differences in circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in US adults.

Background: The presence and interpretation of racial and ethnic differences in circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP), a diagnostic biomarker for heart failure, are controversial. Objective: To examine racial and ethnic differences in NT-proBNP levels among the general US adult population. Methods: We performed a cross-sectional analysis of data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We included 4717 non-Hispanic White, 1675 non-Hispanic Black, and 2148 Mexican American adults aged 20 years or older without a history of cardiovascular disease. We examined the associations of race and ethnicity with NT-proBNP using linear and logistic regression models in the overall population and in a younger, 'healthy' subsample. Results: The mean age was 45 years. Median NT-proBNP levels were significantly lower among Black (29.3 pg/mL) and Mexican American adults (28.3.4 pg/mL) compared to White adults (49.1pg/mL, P-values<0.001). After adjusting for sociodemographic factors and cardiovascular risk factors, NT-proBNP was 34.4% lower (95%CI -39.2 to -29.3%) in Black adults and 22.8% lower (95%CI -29.4 to -15.5) in Mexican American adults compared to White adults. Our findings were consistent in a young, healthy subsample, suggesting non-cardiometabolic determinants of these differences. Conclusions: NT-proBNP levels are significantly lower among Black and Mexican American adults compared with White adults, independent of cardiometabolic risk. Although race/ethnicity is a poor proxy for genetic differences, our findings may have clinical implications for the management of HF. However, studies in diverse populations are needed to characterize the biological basis of NT-proBNP variation.

Elevated Cardiac Biomarkers, Erectile Dysfunction, and Mortality in U.S. Men: NHANES 2001 to 2004.

BACKGROUND: The prevalence of elevated cardiac biomarkers and their link to mortality in men with erectile dysfunction in the U.S. population are unknown. OBJECTIVES: The purpose of this study was to evaluate the prevalence of elevations in N-terminal prohormone B-type natriuretic peptide, high sensitivity troponin (hs-troponin) T, and 3 hs-troponin I assays and their associations with mortality in U.S. men with and without erectile dysfunction. METHODS: We conducted cross-sectional analyses using logistic regression to examine associations of elevated cardiac biomarkers (>90th percentile) with erectile dysfunction in 2,971 male participants aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. We conducted prospective analyses using Cox regression to examine the mortality implications of elevations in cardiac biomarkers in the setting of erectile dysfunction. RESULTS: Elevations in hs-troponin T and the 3 hs-troponin I assays were associated with erectile dysfunction, with the strongest association for hs-troponin T (adjusted OR: 2.01; 95% CI: 1.22-3.30). Elevated N-terminal prohormone B-type natriuretic peptide was not significantly associated with erectile dysfunction (OR: 1.22; 95% CI: 0.74-2.03). There were 673 deaths during a median of 16 years of follow-up. Men with erectile dysfunction were at an elevated risk of death (adjusted HR: 1.23; 95% CI: 1.04-1.46). Those men with elevated cardiac biomarkers in the setting of erectile dysfunction were at highest risk of all-cause and cardiovascular mortality (adjusted HRs ranging from ~1.5 to 2.4). CONCLUSIONS: In this national study, the association of erectile dysfunction with elevated hs-troponin and excess mortality risk suggests that men with erectile dysfunction should be evaluated and targeted for intensive cardiovascular risk management.

Prevalence of Elevated NT-proBNP and its Prognostic Value by Blood Pressure Treatment and Control.

BACKGROUND: The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population. METHODS: We measured NT-proBNP in stored blood samples collected from participants 1 year or older who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults 20 years or older without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories. RESULTS: Among US adults without CVD, the prevalence of elevated NT-proBNP (≥125 pg/ml) was 27.2% among those with untreated hypertension, 24.9% among those with treated controlled hypertension, and 43.3% among those with treated uncontrolled hypertension. Over a median follow-up of 17.3 years and after adjusting for demographic and clinical risk factors, US adults with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and cardiovascular mortality (HR 3.83, 95% CI 2.34, 6.29), compared to adults without hypertension and with low levels of NT-proBNP (<125 pg/ml). Across all levels of SBP and irrespective of antihypertensive medication use, elevated NT-proBNP was associated with an increased risk of mortality, compared to low levels of NT-proBNP. CONCLUSIONS: Among a general population of adults free of CVD, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.

Associations of N-terminal pro-B-type natriuretic peptide, estimated glomerular filtration rate, and mortality in US adults.

BACKGROUND: NT-proBNP is an important predictor of mortality but is inversely related to estimated glomerular filtration rate (eGFR). Whether the prognostic value of NT-proBNP is similar at different levels of kidney function is unknown. AIMS: We evaluated the association of NT-proBNP with eGFR and its implications for all-cause and cardiovascular mortality risk in the general population. METHODS: We included adults without prior cardiovascular disease from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. We used linear regression to characterize the cross-sectional associations of NT-proBNP with eGFR. We used Cox regression to assess the prospective associations of NT-proBNP with mortality across categories of eGFR. RESULTS: Among 11,456 participants (mean age 43 years, 48% female, 71% White, 11% Black), there was an inverse association between NT-proBNP and eGFR, which was stronger in those with more impaired kidney function. Per 15-unit decrease in eGFR, NT-proBNP was 4.3-fold higher for eGFR<30; 1.7-fold higher for eGFR 30 to 60, 1.4-fold higher for eGFR 61 to 90, 1.1-fold higher for eGFR 91 to 120 mL/min/1.73 m2. Over a median 17.6 years of follow-up, 2,275 deaths (622 cardiovascular) occurred. Higher NT-proBNP was associated with higher all-cause (HR per doubling of NT-proBNP: 1.20, 95% CI: 1.16-1.25) and cardiovascular mortality (HR: 1.34, 95% CI 1.25-1.44). Associations were similar across eGFR categories (P-interaction >.10). Adults with NT-proBNP≥450 pg/mL and eGFR<60 mL/min/1.73m2 had 3.4-fold higher all-cause mortality and 5.5-fold higher cardiovascular mortality risk, compared to those with NT-proBNP<125 pg/mL and eGFR>90 mL/min/1.73m2. CONCLUSION: Despite its strong inverse association with eGFR, NT-proBNP has robust associations with mortality across the full range of kidney function in the general US adult population.

Associations of Cardiac Biomarkers With Peripheral Artery Disease and Peripheral Neuropathy in US Adults Without Prevalent Cardiovascular Disease.

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. The aims of our study were to establish the prevalence and associations of elevated NT-proBNP, hs-troponin T, and hs-troponin I with lower extremity disease, including peripheral artery disease (PAD) and peripheral neuropathy (PN), in the US general adult population without known cardiovascular disease. We also assessed whether the combination of PAD or PN and elevated cardiac biomarkers was associated with an increased risk of all-cause and cardiovascular mortality. METHODS: We conducted a cross-sectional analysis of the associations of NT-proBNP, hs-troponin T, and hs-troponin I with PAD (based on ankle-brachial index <0.90) and PN (diagnosed by monofilament testing) in adult participants aged ≥40 years of age without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We calculated the prevalence of elevated cardiac biomarkers among adults with PAD and PN and used multivariable logistic regression to assess the associations of each cardiac biomarker, modeled using clinical cut points, with PAD and PN separately. We used multivariable Cox proportional hazards models to assess the adjusted associations of cross categories of clinical categories of each cardiac biomarker and PAD or PN with all-cause and cardiovascular mortality. RESULTS: In US adults aged ≥40 years, the prevalence (±SE) of PAD was 4.1±0.2% and the prevalence of PN was 12.0±0.5%. The prevalence of elevated NT-proBNP (≥125 ng/L), hs-troponin T (≥6 ng/L), and hs-troponin I (≥6 ng/L for men and ≥4 ng/L for women) was 54.0±3.4%, 73.9±3.5%, and 32.3±3.7%, respectively, among adults with PAD and 32.9±1.9%, 72.8±2.0%, and 22.7±1.9%, respectively, among adults with PN. There was a strong, graded association of higher clinical categories of NT-proBNP with PAD after adjusting for cardiovascular risk factors. Clinical categories of elevated hs-troponin T and hs-troponin I were strongly associated with PN in adjusted models. After a maximum follow-up of 21 years, elevated NT-proBNP, hs-troponin T, and hs-troponin I were each associated with all-cause and cardiovascular mortality, with higher risks of death observed among adults with elevated cardiac biomarkers plus PAD or PN compared with elevated biomarkers alone. CONCLUSIONS: Our study establishes a high burden of subclinical cardiovascular disease defined by cardiac biomarkers in people with PAD or PN. Cardiac biomarkers provided prognostic information for mortality within and across PAD and PN status, supporting the use of these biomarkers for risk stratification among adults without prevalent cardiovascular disease.

NT-proBNP Reference Intervals in Healthy U.S. Children, Adolescents, and Adults.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults. METHODS: We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories. RESULTS: NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348). CONCLUSIONS: Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk.

High-sensitivity troponins and mortality in the general population.

AIMS: Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality. METHODS AND RESULTS: Among adults without cardiovascular disease in the 1999-2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13-1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02-1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14-1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21-1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19-1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09-1.53) for Abbott after adjustment for the Ortho assay. CONCLUSION: This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population.

Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

BACKGROUND: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. OBJECTIVES: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. METHODS: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. RESULTS: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. CONCLUSIONS: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in U.S. Adults.

BACKGROUND: Myocardial injury is currently defined as a cardiac troponin above the sex-specific 99th percentile of a healthy reference population (upper reference limit [URL]). OBJECTIVES: The purpose of this study was to estimate high-sensitivity (hs) troponin URLs in a representative sample of the U.S. adult population; overall and by sex, race/ethnicity, and age group. METHODS: Among adults participating in the 1999-2004 National Health and Nutrition Examination Survey (NHANES), we measured hs-troponin T using 1 assay (Roche) and hs-troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy reference subgroup, we estimated 99th percentile URLs for each assay using the recommended nonparametric method. RESULTS: Of 12,545 participants, 2,746 met criteria for the healthy subgroup (mean age 37 years, 50% men). The NHANES 99th percentile URL for hs-troponin T (19 ng/L) matched the manufacturer-reported URL (19 ng/L). NHANES URLs were 13 ng/L (95% CI: 10-15 ng/L) for Abbott hs-troponin I (manufacturer: 28 ng/L), 5 ng/L (95% CI: 4-7 ng/L) for Ortho hs-troponin I (manufacturer: 11 ng/L), and 37 ng/L (95% CI: 27-66 ng/L) for Siemens hs-troponin I (manufacturer: 46.5 ng/L). There were significant differences in URLs by sex, but none by race/ethnicity. Furthermore, the 99th percentile URLs for all 4 hs-troponin assays were statistically significantly lower in healthy adults aged <40 years compared with healthy adults ≥60 years (all P < 0.001 by rank sum testing). CONCLUSIONS: We found URLs for hs-troponin I assays that were substantially lower than currently listed 99th percentile URLs. There were significant differences in hs-troponin T and I URLs by sex and by age group in healthy U.S. adults but none by race/ethnicity.

Subclinical Cardiovascular Disease in US Adults With and Without Diabetes.

Background We characterized the burden and prognostic value of subclinical cardiovascular disease (CVD) assessed by cardiac biomarkers among adults with and without diabetes in the general US population. Methods and Results We measured hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum samples from the 1999 to 2004 National Health and Nutrition Examination Survey. Among US adults without a history of CVD (n=10 304), we estimated the prevalence of elevated hs-cTnT (≥14 ng/L) and NT-proBNP (≥125 pg/mL) in those with and without diabetes. We examined the associations between elevated hs-cTnT and NT-proBNP with all-cause and CVD mortality after adjustment for demographics and traditional CVD risk factors. The crude prevalence of subclinical CVD (elevated hs-cTnT or NT-proBNP) was ≈2 times higher in adults with (versus without) diabetes (33.4% versus 16.1%). After age adjustment, elevated hs-cTnT, but not elevated NT-proBNP, was more common in those with diabetes, overall and across age, sex, race and ethnicity, and weight status. The prevalence of elevated hs-cTnT was significantly higher in those with longer diabetes duration and worse glycemic control. In persons with diabetes, elevated hs-cTnT and NT-proBNP were independently associated with all-cause mortality (adjusted hazard ratio [HR], 1.77 [95% CI, 1.33-2.34] and HR, 1.78 [95% CI, 1.26-2.51]) and CVD mortality (adjusted HR, 1.54 [95% CI, 0.83-2.85] and HR, 2.46 [95% CI, 1.31-4.60]). Conclusions Subclinical CVD affects ≈1 in 3 US adults with diabetes and confers substantial risk for mortality. Routine testing of cardiac biomarkers may be useful for assessing and monitoring risk in persons with diabetes.

NT-proBNP and All-Cause and Cardiovascular Mortality in US Adults: A Prospective Cohort Study.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is strongly associated with mortality in patients with heart failure. Prior studies, primarily in middle-aged and older populations, have suggested that NT-proBNP has prognostic value in ambulatory adults. Methods and Results We conducted a prospective cohort analysis of adults, aged ≥20 years, in the nationally representative 1999 to 2004 National Health and Nutrition Examination Survey, to characterize the association of NT-proBNP with mortality in the general US adult population overall and by age, race and ethnicity, and body mass index. We used Cox regression to characterize associations of NT-proBNP with all-cause and cardiovascular disease (CVD) mortality through 2019, adjusting for demographics and cardiovascular risk factors. We included 10 645 individuals (mean age, 45.7 years; 50.8% women; 72.8% White adults; 8.5% with a self-reported history of CVD). There were 3155 deaths (1009 CVD-related) over a median 17.3 years of follow-up. Among individuals without prior CVD, elevated NT-proBNP (≥75th percentile [81.5 pg/mL] versus <25th percentile [20.5 pg/mL]) was associated with a significantly higher risk of all-cause (hazard ratio [HR], 1.67 [95% CI, 1.39-2.00]) and CVD mortality (HR, 2.87 [95% CI, 1.61-5.11]). Associations of NT-proBNP with all-cause and CVD mortality were generally similar across subgroups defined by age, sex, race and ethnicity, or body mass index (all P interaction >0.05). Conclusions In a representative sample of the US adult population, NT-proBNP was an important independent risk factor for all-cause and CVD mortality. NT-proBNP may be useful for monitoring risk in the general adult population.

Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in a Population-Based Sample of US Children and Adolescents.

BACKGROUND: Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin. METHODS: Among participants 1 to 18 years of age in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method. RESULTS: Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12-17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12-19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25-46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race and ethnicity-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children and adolescents, 97.5th percentile URLs were 11 ng/L (95% CI, 10-12) versus 6 ng/L (95% CI, 6-7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7-10) versus 5 ng/L (95% CI, 4-6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18-25) versus 11 ng/L (95% CI, 9-13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3-5) versus 2 ng/L (95% CI, 1-3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for high-sensitivity troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. CONCLUSIONS: Because myocardial infarction is rare in children and adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile high-sensitivity troponin URLs might be considered to define pediatric myocardial injury.

Prevalence of Elevated NT-proBNP and its Prognostic Value by Blood Pressure Treatment and Control- National Health and Nutrition Examination Survey, 1999-2004.

Background: The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population. Methods: We measured NT-proBNP among adults aged 20 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories. Results: The number of US adults without CVD with elevated NT-proBNP (≥125 pg/ml) was 6.2 million among those with untreated hypertension, 4.6 million among those with treated controlled hypertension, and 5.4 million among those with treated uncontrolled hypertension. After adjusting for age, sex, body mass index, and race/ethnicity, participants with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and increased risk of cardiovascular mortality (HR 3.83, 95% CI: 2.34, 6.29), compared to those without hypertension and with low levels of NT-proBNP (<125 pg/ml). Among those on antihypertensive medication, those with SBP 130-139 mm Hg and elevated NT-proBNP had increased risk of all-cause mortality, compared to those with SBP<120 mm Hg and low levels of NT-proBNP. Conclusions: Among a general population of adults free of cardiovascular disease, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.

Identification of Protein Biomarkers of the Dietary Approaches to Stop Hypertension Diet in Randomized Feeding Studies and Validation in an Observational Study.

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large-scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8-week and 4-week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH-Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta-analyzed using fixed-effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate <0.05, there were 71 proteins that were different between the DASH diet and control diet in the DASH and DASH-Sodium trials. Nineteen proteins were validated in the ARIC study. The 19 proteins collectively improved the prediction of the DASH diet intervention in the feeding studies (range of difference in C statistics, 0.267-0.313; P<0.001 for both tests) and the DASH diet score in the ARIC study (difference in C statistics, 0.017; P<0.001) beyond participant characteristics. Conclusions We identified 19 proteins robustly associated with the DASH diet in 3 studies, which may serve as biomarkers of the DASH diet. These results suggest potential pathways that are impacted by consumption of the DASH diet. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03403166, NCT00000608.