Association of Lipoprotein (a) with peri-coronary inflammation in persons with and without HIV infection.

BACKGROUND: Persons with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD) compared to persons without HIV (PWoH). Lipoprotein a (Lp(a)) is a known atherosclerotic risk factor in PWoH, but there are no studies investigating Lp(a) and peri-coronary inflammation. OBJECTIVE: To investigate whether Lp(a) is associated with peri-coronary inflammation as assessed by the fat attenuation index (FAI) and activated monocytes and T lymphocytes in PWH and PWoH. METHODS: We measured plasma levels of Lp(a) at study entry in 58 PWH and 21 PWoH without CVD and who had FAI measurements. Associations of Lp(a) with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were evaluated using multivariable regression models adjusted for potential confounders. Correlations between Lp(a) levels and systemic inflammatory markers and immune cell subsets were examined. RESULTS: Lp(a) was associated with greater peri-coronary inflammation among PWH compared to PWoH (ß=1.73, P=0.019) in the RCA, in adjusted models. Significant correlations were observed with certain inflammatory markers (TNFR-I, b=0.295, P<0.001; TNFR-II, b=0.270, P=0.002; hs-CRP, b=0.195, P=0.028). Significant correlations were found between Lp(a) levels and several markers of monocyte activation: CD16 -CD163+ (b= -0.199, P=0.024), and CD16 -DR+ MFI (b= -0.179, P=0.042) and T cell subset CD38+CD4+ TEMRA (b= 0.177, P= 0.044). CONCLUSIONS: Lp(a) was associated with greater peri-coronary inflammation in the RCA in PWH compared to PWoH, as well as with select systemic inflammatory markers and specific subsets of immune cells in peripheral circulation.

Joint Associations of Pregnancy Complications and Postpartum Maternal Renal Biomarkers With Severe Cardiovascular Morbidities: A US Racially and Ethnically Diverse Prospective Birth Cohort Study.

Background Pregnancy complications are risk factors for cardiovascular disease (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods and Results This study included 566 mothers of diverse races and ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and CysC (cystatin C) were measured 1 to 3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. During an average of 10.3±3.2 years of follow-up, 30 mothers developed 1 or more CVDs. Only a modest association was observed between creatinine and risk of CVD. In comparison, we found that per 0.1 mg/L increase of CysC was associated with a hazard ratio (HR) of 1.2 (95% CI, 1.1-1.4) for CVD after adjusting for covariates. Compared with those without preeclampsia and with normal CysC level (≤75th percentile), mothers with preeclampsia and elevated CysC (>75th percentile) had the highest risk of CVD (HR, 4.6 [95% CI, 1.7-17.7]), whereas mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery. Conclusions In this sample of US, traditionally underrepresented multiracial and multiethnic high-risk mothers, elevated maternal plasma CysC, independently and jointly with pregnancy complications, increased risk of CVD later in life. These findings warrant further investigation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03228875.

Joint associations of pregnancy complications and postpartum maternal renal biomarkers with severe cardiovascular morbidities: A US racially diverse prospective birth cohort study.

Rationale & Objective: Pregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods: This study included 576 mothers of diverse ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and cystatin C were measured 1-3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. Results: During an average of 10.3±3.2 years of follow-up, 34 mothers developed one or more CVD events. Although no significant associations were found between creatinine and risk of CVD, per unit increase of cystatin C (CysC) was associated with a hazard ratio (HR) of 5.21 (95%CI = 1.49-18.2) for CVD. A borderline significant interactive effect was observed between elevated CysC (≥75th percentile) and preeclampsia. Compared to those without preeclampsia and with normal CysC level (<75 th percentile), mothers with preeclampsia and elevated CysC had the highest risk of CVD (HR=3.8, 95%CI = 1.4-10.2), while mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery. Conclusions: In this sample of US, traditionally under-represented multi-ethnic high-risk mothers, elevated maternal plasma cystatin C and pregnancy complications synergistically increased risk of CVD later in life. These findings warrant further investigation. Clinical Perspectives: What is new?Maternal postpartum elevated levels of cystatin C are independently associated with higher risk of cardiovascular diseases (CVD) later in life.Maternal pregnancy complications coupled with postpartum elevated levels of cystatin C synergistically increased future risk of CVD.What are the clinical implications?These findings, if further confirmed, suggest that women with pregnancy complications and elevated postpartum cystatin C may be at particular high risk for CVD later in life compared to women without these risk factors.

Effects of the Dietary Approaches to Stop Hypertension Diet on Change in Cardiac Biomarkers Over Time: Results From the DASH-Sodium Trial.

Background The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high-sensitivity cardiac troponin I), cardiac strain (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and inflammation (hs-CRP [high-sensitivity C-reactive protein]) while consuming the DASH diet. Methods and Results The DASH-Sodium trial was a randomized controlled trial of 412 adults with elevated blood pressure or hypertension. Participants were randomly assigned to 12 weeks of the DASH diet or a typical American diet. Energy intake was adjusted to maintain body weight. Measurements of high-sensitivity cardiac troponin I, NT-proBNP, and hs-CRP were performed in stored serum specimens, collected at baseline and ≈4, 8, and 12 weeks after randomization. In both the control diet and DASH diet, levels of NT-proBNP decreased; however, there was no difference between diets (P-trend compared with control=0.22). On the DASH diet versus control, levels of high-sensitivity cardiac troponin I decreased progressively during follow-up (P-trend compared with control=0.025), but a statistically significant between-diet difference in change from baseline levels was not observed until week 12 (% difference, 17.78% [95% CI, -29.51% to -4.09%]). A similar pattern was evident for hs-CRP (P-trend compared with control=0.01; % difference at week 12, 19.97% [95% CI, -31.94% to -5.89%]). Conclusions In comparison with a typical American diet, the DASH diet reduced high-sensitivity cardiac troponin I and hs-CRP progressively over 12 weeks. These results suggest that the DASH diet has cumulative benefits over time on biomarkers of subclinical cardiac injury and inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000608.

Patterns of Daily Physical Movement, Chronic Inflammation, and Frailty Incidence.

INTRODUCTION: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation-a pathway often underlying frailty-remains unexplored. METHODS: Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined. RESULTS: Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d -1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% ( P = 0.003), 13% ( P = 0.001), and 8% ( P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all). CONCLUSIONS: Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal.

Distribution of High-Sensitivity Cardiac Troponin and N-Terminal Pro-Brain Natriuretic Peptide in Healthy Transgender People.

Importance: Sex-specific differences in the commonly used cardiac biomarkers high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are apparent. There is an absence of medical literature delineating the concentration differences for these biomarkers in transgender individuals without cardiac disease. Objective: To determine the distribution of hs-cTn and NT-proBNP in healthy transgender people. Design, Setting, and Participants: In this cross-sectional prospective study, healthy transgender individuals prescribed testosterone or estradiol for 12 months or more were recruited from internal medicine and primary care clinics that specialize in transgender medical care between November 1, 2017, and July 1, 2018. Exposures: Testosterone or estradiol for 12 months. Main Outcomes and Measures: Concentrations for hs-cTnI (troponin I), hs-cTnT (troponin T), and NT-proBNP were measured. Results: Transgender people prescribed testosterone (n = 79; mean [SD] age, 28.8 [7.8] years) or estrogen (n = 93; mean [SD] age, 35.1 [11.7] years) were recruited. The concentration of hs-cTn was significantly higher in transgender men relative to transgender women. For Abbott hs-cTnI levels, the median (IQR) concentration observed in transgender men and women was 0.9 (0.6-1.7) ng/L and 0.6 (0.3-1.0) ng/L, respectively. Results were similar across 2 additional hs-cTn assays. In contrast, NT-proBNP level was higher in transgender women. The median (IQR) NT-proBNP concentration was significantly higher in transgender women ( 49 [32-86] ng/L) than in transgender men (17 [13-27] ng/L). Conclusions and Relevance: Findings of this cross-sectional study suggest that the differences in concentration for hs-cTn and NT-proBNP between transgender men and women were similar to what is observed between cisgender men and women. Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease.

Effects of Diet and Sodium Reduction on Cardiac Injury, Strain, and Inflammation: The DASH-Sodium Trial.

BACKGROUND: The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown. OBJECTIVES: The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation. METHODS: DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period. RESULTS: Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: -27% to -7%) and hs-CRP by 13% (95% CI: -24% to -1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: -24% to -14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: -31% to -7%) and NT-proBNP by 23% (95% CI: -32% to -12%), whereas hs-CRP was not significantly changed (-7%; 95% CI: -22% to 9%) compared with the high sodium-control diet. CONCLUSIONS: Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH - Sodium]; NCT00000608).

Performance of 4 Automated SARS-CoV-2 Serology Assay Platforms in a Large Cohort Including Susceptible COVID-19-Negative and COVID-19-Positive Patients.

BACKGROUND: Anti-SARS-CoV-2 serological responses may have a vital role in controlling the spread of the disease. However, the comparative performance of automated serological assays has not been determined in susceptible patients with significant comorbidities. METHODS: In this study, we used large numbers of samples from patients who were negative (n = 2030) or positive (n = 112) for COVID-19 to compare the performance of 4 serological assay platforms: Siemens Healthineers Atellica IM Analyzer, Siemens Healthineers Dimension EXL Systems, Abbott ARCHITECT, and Roche cobas. RESULTS: All 4 serology assay platforms exhibited comparable negative percentage of agreement with negative COVID-19 status ranging from 99.2% to 99.7% and positive percentage of agreement from 84.8% to 87.5% with positive real-time reverse transcriptase PCR results. Of the 2142 total samples, only 38 samples (1.8%) yielded discordant results on one or more platforms. However, only 1.1% (23/2030) of results from the COVID-19-negative cohort were discordant. whereas discordance was 10-fold higher for the COVID-19-positive cohort, at 11.3% (15/112). Of the total 38 discordant results, 34 were discordant on only one platform. CONCLUSIONS: Serology assay performance was comparable across the 4 platforms assessed in a large population of patients who were COVID-19 negative with relevant comorbidities. The pattern of discordance shows that samples were discordant on a single assay platform, and the discordance rate was 10-fold higher in the population that was COVID-19 positive.

Associations Between Dietary Patterns and Subclinical Cardiac Injury: An Observational Analysis From the DASH Trial.

BACKGROUND: The DASH diet has been found to lower blood pressure (BP) and low-density lipoprotein cholesterol levels. OBJECTIVE: To compare diets rich in fruits and vegetables with a typical American diet in their effects on cardiovascular injury in middle-aged adults without known preexisting cardiovascular disease (CVD). DESIGN: Observational study based on a 3-group, parallel-design, randomized trial conducted in the United States from 1994 to 1996. (ClinicalTrials.gov: NCT00000544). SETTING: 3 of the 4 original clinical trial centers. PARTICIPANTS: 326 of the original 459 trial participants with available stored specimens. INTERVENTION: Participants were randomly assigned to 8 weeks of monitored feeding with a control diet typical of what many Americans eat; a diet rich in fruits and vegetables but otherwise similar to the control diet; or the DASH diet, which is rich in fruits, vegetables, low-fat dairy, and fiber and has low levels of saturated fat and cholesterol. Weight was kept constant throughout feeding. MEASUREMENTS: Biomarkers collected at baseline and 8 weeks: high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). RESULTS: The mean age of participants was 45.2 years, 48% were women, 49% were black, and mean baseline BP was 131/85 mm Hg. Compared with the control diet, the fruit-and-vegetable diet reduced hs-cTnI levels by 0.5 ng/L (95% CI, -0.9 to -0.2 ng/L) and NT-proBNP levels by 0.3 pg/mL (CI, -0.5 to -0.1 pg/mL). Compared with the control diet, the DASH diet reduced hs-cTnI levels by 0.5 ng/L (CI, -0.9 to -0.1 ng/L) and NT-proBNP levels by 0.3 pg/mL (CI, -0.5 to -0.04 pg/mL). Levels of hs-CRP did not differ among diets. None of the markers differed between the fruit-and-vegetable and DASH diets. LIMITATION: Short duration, missing specimens, and an inability to isolate the effects of specific foods or micronutrients. CONCLUSION: Diets rich in fruits and vegetables given over 8 weeks were associated with lower levels of markers for subclinical cardiac damage and strain in adults without preexisting CVD. PRIMARY FUNDING SOURCE: National Institutes of Health, National Heart, Lung, and Blood Institute.

Healthy diet reduces markers of cardiac injury and inflammation regardless of macronutrients: Results from the OmniHeart trial.

BACKGROUND: Despite diet being a first-line strategy for preventing cardiovascular disease, the optimal macronutrient profile remains unclear. We studied the effects of macronutrient profile on subclinical cardiovascular injury and inflammation. METHODS: OmniHeart was a randomized 3-period, crossover feeding study in 164 adults with high blood pressure or hypertension (SBP 120-159 or DBP 80-99 mm Hg). Participants were fed each of 3 diets (emphasizing carbohydrate (CARB), protein (PROT), or unsaturated fat (UNSAT)) for 6-weeks, with feeding periods separated by a washout period. Weight was held constant. Fasting serum was collected at baseline while participants ate their own diets and after each feeding period. High-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity C-reactive protein (hs-CRP) were measured in stored specimens. RESULTS: The average age was 53.6 years, 55% were African American, and 45% were women. At baseline, the median (25th-percentile, 75th-percentile) hs-cTnI was 3.3 ng/L (1.9, 5.6) and hs-CRP was 2.2 mg/L (1.1, 5.2). Compared to baseline, all 3 diets reduced hs-cTnI: CARB -8.6% (95%CI: -16.1, -0.4), PROT -10.8% (-18.4, -2.5), and UNSAT -9.4% (-17.4, -0.5). Hs-CRP was similarly changed by -13.9 to -17.0%. Hs-cTnI and hs-CRP reductions were of similar magnitudes as SBP and low-density lipoprotein cholesterol (LDLc) but were not associated with these risk-factor reductions (P-values = 0.09). There were no between-diet differences in hs-cTnI and hs-CRP reductions. CONCLUSIONS: Healthy diet, regardless of macronutrient emphasis, directly mitigated subclinical cardiac injury and inflammation in a population at risk for cardiovascular disease. These findings support dietary recommendations emphasizing healthy foods rather than any one macronutrient. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov, number: NCT00051350; URL: https://clinicaltrials.gov/ct2/show/NCT00051350.

Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction.

OBJECTIVES: Concentrations of endothelin I (ET1) are elevated in CHF patients and, like other biomarkers that reflect hemodynamic status and cardiac pathophysiology, are prognostic. The Singulex assay (Sgx-ET1) measures the active form of ET1, with a short in vivo half-life and the Brahms assay measures C-terminal endothelin-1 (CT-ET1), a modified (degraded) product with longer half-life. We aimed to determine the prognostic importance of active and modified forms of endothelin 1 (Singulex and Brahms assays) in comparison with other commonly measured biomarkers of inflammation, hemodynamic status and cardiac physiology in CHF. DESIGN AND METHODS: Plasma biomarkers (Sgx-ET1, CT-ET1, NTproBNP, IL-6, TNFα, cTnI, VEGF, hs-CRP, Galectin-3, ST2) were measured in 134 NYHA class II and III CHF patients with systolic dysfunction. Prognostic importance of biomarkers for hospitalization or death were calculated by both logistic regression and Kaplan-Meier survival analyses. RESULTS: CT-ET1 (OR=5.2, 95% CI=1.7-15.7) and Sgx-ET1 (OR=2.9, CI=1.1-7.7) were independent predictors of hospitalization and death and additively predicted events after adjusting for age, sex, and other significant biomarkers. Other biomarkers did not improve the model. Similarly, in Cox regression analysis, only CT-ET1 (HR 3.4, 95% CI=1.4-8.4), VEGF (2.7, 95% CI=1.3-5.4), and Sgx-ET1 (HR 2.6, 95% CI=1.2-5.6) were independently prognostic. CONCLUSIONS: Elevated concentrations of endothelin 1 predict mortality and hospitalizations in HF patients. Endothelin 1 was more prognostic than commonly obtained hemodynamic, inflammatory, and fibrotic biomarkers. Two different assays of endothelin 1 independently and synergistically were prognostic, suggesting either complementary information or extreme prognostic importance.

Analytical performance and clinical concordance of the cancer biomarkers CA 15-3, CA 19-9, CA 125 II, Carcinoembryonic Antigen, and Alpha-Fetoprotein on the Dimension Vista® System.

OBJECTIVES: We examined analytical characteristics of new CA 15-3, CA 19-9, CA 125 II, Carcinoembryonic Antigen (CEA), and Alpha-Fetoprotein (AFP) assays on the Dimension Vista® System. DESIGN AND METHODS: Imprecision studies used CLSI-EP5-A2, Limit of Blank and Limit of Detection used CLSI-EP17 and measurement ranges were determined. Method comparisons were evaluated with Passing-Bablok, least-squares regression and residual plots. Reference intervals were determined and valid specimen types, lot-to-lot variability and sample storage stability were defined. Clinical monitoring patterns for each tumor marker in patients were examined. RESULTS: Reproducibility for each method was <6.5%. Limits of Blank and Detection were low. Comparisons between methods showed slopes ranging from 0.89 to 1.32 with low y-intercepts and scatter. Minimal lot-to-lot variability was documented; serum/plasma specimens provide valid results; sample stability at -70°C was >9months. Clinical monitoring patterns correlated with established methods in >89% of cases. CONCLUSIONS: Measurement of CA 15-3, CA 19-9, CA 125 II, CEA and AFP on the Dimension Vista® System is an attractive alternative.