Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.

Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with 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% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk. METHODS: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension. RESULTS: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs. CONCLUSIONS: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

BACKGROUND: Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease. METHODS AND RESULTS: Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable-adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all-cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2-year follow-up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable-adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69-0.95) for CVD, 0.82 (0.70-0.97) for ESKD, and 0.80 (0.72-0.89) for mortality. CONCLUSIONS: Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all-cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.

Neighborhood-level social determinants of health and cardioprotective behaviors among church members in New Orleans, Louisiana.

BACKGROUND: Favorable neighborhood-level social determinants of health (SDoH) are associated with lower cardiovascular disease risk. Less is known about their influence on cardioprotective behaviors. We evaluated the associations between neighborhood-level SDoH and cardioprotective behaviors among church members in Louisiana. METHODS: Participants were surveyed between November 2021 to February 2022, and were asked about health behaviors, aspects of their neighborhood, and home address (to link to census tract and corresponding social deprivation index [SDI] data). Logistic regression models were used to assess the relation of neighborhood factors with the likelihood of engaging in cardioprotective behaviors: 1) a composite of healthy lifestyle behaviors [fruit and vegetable consumption, physical activity, and a tobacco/nicotine-free lifestyle], 2) medication adherence, and 3) receipt of routine medical care within the past year. RESULTS: Participants (n = 302, mean age: 63 years, 77% female, 99% Black) were recruited from 12 churches in New Orleans. After adjusting for demographic and clinical factors, perceived neighborhood walkability or conduciveness to exercise (odds ratio [OR]=1.25; 95% CI: 1.03, 1.53), availability of fruits and vegetables (OR=1.23; 95% CI: 1.07, 1.42), and social cohesion (OR=1.55; 95% CI: 1.22, 1.97) were positively associated with the composite of healthy lifestyle behaviors. After multivariable adjustment, SDI was in the direction of association with all three cardioprotective behavior outcomes, but associations were not statistically significant. CONCLUSIONS: In this predominantly Black, church-based population, neighborhood-level SDoH including the availability of fruits and vegetables, walkability or conduciveness to exercise, and social cohesion were associated with cardioprotective behaviors. Findings reiterate the need to address adverse neighborhood-level SDoH in the design and implementation of health interventions.

Social, Behavioral, and Metabolic Risk Factors and Racial Disparities in Cardiovascular Disease Mortality in U.S. Adults : An Observational Study.

BACKGROUND: Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States. OBJECTIVE: To examine the degree to which social, behavioral, and metabolic risk factors are associated with CVD mortality and the extent to which racial differences in CVD mortality persist after these factors are accounted for. DESIGN: Prospective cohort study. SETTING: NHANES (National Health and Nutrition Examination Survey) 1999 to 2018. PARTICIPANTS: A nationally representative sample of 50 808 persons aged 20 years or older. MEASUREMENTS: Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. Deaths from CVD were ascertained from linkage to the National Death Index with follow-up through 2019. RESULTS: Over an average of 9.4 years of follow-up, 2589 CVD deaths were confirmed. The age- and sex-standardized rates of CVD mortality were 484.7 deaths per 100 000 person-years in Black participants, 384.5 deaths per 100 000 person-years in White participants, 292.4 deaths per 100 000 person-years in Hispanic participants, and 255.1 deaths per 100 000 person-years in other race groups. In a multiple Cox regression analysis adjusted for all measured risk factors simultaneously, several social (unemployment, low family income, food insecurity, lack of home ownership, and unpartnered status), behavioral (current smoking, lack of leisure-time physical activity, and sleep <6 or >8 h/d), and metabolic (obesity, hypertension, and diabetes) risk factors were associated with a significantly higher risk for CVD death. After adjustment for these metabolic, behavioral, and social risk factors separately, hazard ratios of CVD mortality for Black compared with White participants were attenuated from 1.54 (95% CI, 1.34 to 1.77) to 1.34 (CI, 1.16 to 1.55), 1.31 (CI, 1.15 to 1.50), and 1.04 (CI, 0.90 to 1.21), respectively. LIMITATION: Causal contributions of social, behavioral, and metabolic risk factors to racial and ethnic disparities in CVD mortality could not be established. CONCLUSION: The Black-White difference in CVD mortality diminished after adjustment for behavioral and metabolic risk factors and completely dissipated with adjustment for social determinants of health in the U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.

Examination of Serum Metabolome Altered by Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites Associated with Blood Pressure: The ProBP Trial.

SCOPE: This study aims to discover metabolites of dietary carbohydrate, soy and milk protein supplements and evaluate their roles in blood pressure (BP) regulation in the protein and blood pressure (ProBP), a cross-over trial. METHODS AND RESULTS: Plasma metabolites are profiled at pre-trial baseline and after 8 weeks of supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. After Bonferroni correction (α = 6.49 × 10-4 ), dietary interventions significantly changed 40 metabolites. Changes of erucate (22:1n9), an omega-9 fatty acid, are positively associated with systolic BP changes (Beta = 1.90, p = 6·27 × 10-4 ). This metabolite is also associated with higher odds of hypertension among 1261 participants of an independent cohort (odds ratio per unit increase = 1.34; 95% confidence interval: 1.07-1.68). High levels of acylcholines dihomo-linolenoyl-choline (p = 4.71E-04) and oleoylcholine (p = 3.48E-04) at baseline predicted larger BP lowering effects of soy protein. Increasing cheese intake during the trial, as reflected by isobutyrylglycine and isovalerylglycine, reduces the BP lowering effect of soy protein. CONCLUSIONS: The study identifies molecular signatures of dietary interventions. Erucate (22:1n9) increases systolic BP. Acylcholine enhances and cheese intake reduces the BP lowering effect of soy protein supplement.

Social determinants of health and premature death among adults in the USA from 1999 to 2018: a national cohort study.

BACKGROUND: Racial and ethnic disparities in mortality persist in the US population. We studied the contribution of social determinants of health (SDoH) to racial and ethnic disparities in premature death. METHODS: A nationally representative sample of individuals aged 20-74 years who participated in the US National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were included. Self-reported SDoH (employment, family income, food security, education, access to health care, health insurance, housing instability, and being married or living with a partner) were collected in each survey cycle. Participants were categorised into four groups of race and ethnicity: Black, Hispanic, White, and other. Deaths were ascertained from linkage to the National Death Index with follow-up until 2019. Multiple mediation analysis was used to assess simultaneous contributions of each individual SDoH to racial disparities in premature all-cause mortality. FINDINGS: We included 48 170 NHANES participants in our analyses, consisting of 10 543 (21·9%) Black participants, 13 211 (27·4%) Hispanic participants, 19 629 (40·7%) White participants, and 4787 (9·9%) participants of other racial and ethnic groups. Mean survey-weighted age was 44·3 years (95% CI 44·0-44·6), 51·3% (50·9-51·8) of participants were women, and 48·7% (48·2-49·1) were men. 3194 deaths before age 75 years were recorded (930 Black participants, 662 Hispanic participants, 1453 White participants, and 149 other participants). Black adults had significantly higher premature mortality than other racial and ethnic groups (p<0·0001): premature death rates per 100 000 person-years were 852 (95% CI 727-1000) for Black adults, 445 (349-574) for Hispanic adults, 546 (474-630) for White adults, and 521 (336-821) for other adults. Unemployment, lower family income, food insecurity, less than high school education, no private health insurance, and not being married nor living with a partner were significantly and independently associated with premature death. Dose-response associations were observed between cumulative number of unfavourable SDoH and premature all-cause mortality: hazard ratios (HRs) were 1·93 (95% CI 1·61-2·31) for those with one unfavourable SDoH, 2·24 (1·87-2·68) for those with two, 3·98 (3·34-4·73) for those with three, 4·78 (3·98-5·74) for those with four, 6·08 (5·06-7·31) for those with five, and 7·82 (6·60-9·26) for those with six or more unfavourable SDoH (p<0·0001 for linear trend). After adjusting for SDoH, HRs for premature all-cause mortality for Black adults compared with White adults decreased from 1·59 (1·44-1·76) to 1·00 (0·91-1·10), suggesting complete mediation of this racial difference in mortality. INTERPRETATION: Unfavourable SDoH are associated with increased rates of premature death and contribute to differences between Black and White racial groups in premature all-cause mortality in the US population. Innovative public health policies and interventions targeting SDoH are needed to reduce premature deaths and health disparities in this population. FUNDING: US National Institutes of Health.

Engaging Predominantly Black Churches in an Intervention to Improve Cardiovascular Health and Reduce Racial Inequities.

Cardiovascular disease (CVD) is the leading cause of mortality in the United States and disproportionately impacts Black adults. Effective implementation of interventions to improve cardiovascular health in the Black community is needed to reduce health inequities. The Church-Based Health Intervention to Eliminate Health Inequalities in Cardiovascular Health (CHERISH) study is implementing interventions recommended by the 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD in Black communities to improve cardiovascular health and reduce health disparities. The recently completed 3-year planning phase of CHERISH has focused on engaging with the predominantly Black church community in New Orleans with the goals of informing study protocol development and recruiting churches for study participation. Community engagement approaches include convening a community advisory board (CAB), conducting qualitative and quantitative needs assessments, and hosting and attending church events. These activities have resulted in an engaged CAB that has contributed meaningfully to planning activities and the study protocol. The needs assessment found that while there are substantial barriers to cardiovascular health, such as knowledge, access to healthy foods, and safe spaces for physical activity, people are willing to make lifestyle changes and think that the proposed intervention components are feasible. Community engagement activities have resulted in the recruitment of 50 geographically and denominationally diverse predominantly Black churches willing to participate in the study (exceeding our goal of 42). Overall, a multicomponent approach to extensive community engagement has produced effective church enrollment for study participation and meaningful input on study design and implementation.

Longer-Term All-Cause and Cardiovascular Mortality With Intensive Blood Pressure Control: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown. Objective: To evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022. Interventions: Randomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: Extended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined. Results: Among 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization. Conclusions and Relevance: The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Intensive Blood Pressure Treatment Goals: Evidence for Cardiovascular Protection From Observational Studies and Clinical Trials.

Epidemiologic studies have consistently identified a strong, progressive relationship between blood pressure (BP) and cardiovascular disease (CVD) events, in a range of systolic BP (SBP) from as low as 90 mm Hg to as high as 180 mm Hg. Clinical trials have demonstrated greater prevention of CVD with more compared with less intensive antihypertensive drug treatment. Meta-analyses of randomized controlled trials provide strong evidence for more intensive antihypertensive drug therapy down to an SBP of 130 mm Hg, and to an SBP 120-124 mm Hg in the meta-analysis with the greatest statistical power. In the Systolic Blood Pressure Intervention Trial (SPRINT) randomization to an SBP treatment goal of <120 mm Hg compared with <140 mm Hg in persons with high CVD risk not only reduced the rate of CVD but also all-cause mortality. These benefits were noted in all of the prestated subgroups of interest, including those ≥65 years of age at baseline. In addition, cognitive impairment was less common in those randomized to the intensive compared with standard treatment. Most clinical practice guidelines recommend an SBP treatment target <130 mm Hg in adults with a high risk of CVD, which is the norm for many patients seen in clinical practice, especially those who are older, have diabetes mellitus, or chronic kidney disease.

Lifestyle behaviors and cardiovascular risk profiles among parous women by gestational diabetes status, 2007-2018.

BACKGROUND AND AIMS: Women with prior gestational diabetes mellitus (GDM) are at elevated risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors among parous U.S. women ages 20-44 by history of GDM. METHODS AND RESULTS: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, 3537 parous women were classified by self-reported GDM history. We compared anthropometric measures, glycemia, blood pressure, lipids, lifestyle factors, cardiovascular health, and cardiometabolic disease prevalence by GDM status. NHANES survey design was taken into account. Women without history of GDM were younger and, after adjusting for age, race/ethnicity, and education, had more favorable cardiometabolic risk factor profiles for measures of anthropometry, glycemia, diabetes, many lipids, physical activity, diet, and overall cardiovascular health than women with history of GDM. Many patterns persisted after further adjustment for lifestyle factors. In analyses stratified by race/ethnicity, many patterns persisted, though there were key differences. Hypertension prevalence differed by GDM history only among Hispanic women. In women of other race/ethnicity, there was no difference in healthy eating or body mass index by GDM history. In non-Hispanic Black women, there was no difference in healthy eating by GDM history. CONCLUSION: Among parous U.S. women ages 20-44, those with history of GDM had less favorable cardiometabolic risk factor profiles than those without history of GDM. This highlights the importance of continued efforts to develop and test multilevel interventions to improve cardiometabolic risk factors among reproductive-age women with a history of GDM.

Risk Prediction Models for Atherosclerotic Cardiovascular Disease in Patients with Chronic Kidney Disease: The CRIC Study.

BACKGROUND: Individuals with CKD may be at high risk for atherosclerotic cardiovascular disease (ASCVD). However, there are no ASCVD risk prediction models developed in CKD populations to inform clinical care and prevention. METHODS: We developed and validated 10-year ASCVD risk prediction models in patients with CKD that included participants without self-reported cardiovascular disease from the Chronic Renal Insufficiency Cohort (CRIC) study. ASCVD was defined as the first occurrence of adjudicated fatal and nonfatal stroke or myocardial infarction. Our models used clinically available variables and novel biomarkers. Model performance was evaluated based on discrimination, calibration, and net reclassification improvement. RESULTS: Of 2604 participants (mean age 55.8 years; 52.0% male) included in the analyses, 252 had incident ASCVD within 10 years of baseline. Compared with the American College of Cardiology/American Heart Association pooled cohort equations (area under the receiver operating characteristic curve [AUC]=0.730), a model with coefficients estimated within the CRIC sample had higher discrimination (P=0.03), achieving an AUC of 0.736 (95% confidence interval [CI], 0.649 to 0.826). The CRIC model developed using clinically available variables had an AUC of 0.760 (95% CI, 0.678 to 0.851). The CRIC biomarker-enriched model had an AUC of 0.771 (95% CI, 0.674 to 0.853), which was significantly higher than the clinical model (P=0.001). Both the clinical and biomarker-enriched models were well-calibrated and improved reclassification of nonevents compared with the pooled cohort equations (6.6%; 95% CI, 3.7% to 9.6% and 10.0%; 95% CI, 6.8% to 13.3%, respectively). CONCLUSIONS: The 10-year ASCVD risk prediction models developed in patients with CKD, including novel kidney and cardiac biomarkers, performed better than equations developed for the general population using only traditional risk factors.

Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race : A Prospective Cohort Study.

BACKGROUND: New estimated glomerular filtration rate (eGFR) equations removed race adjustment, but the impact of its removal on prediction of end-stage kidney disease (ESKD) is unknown. OBJECTIVE: To compare the ESKD prediction performance of different eGFR equations. DESIGN: Observational, prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 3873 participants with chronic kidney disease (CKD) from the CRIC (Chronic Renal Insufficiency Cohort) Study contributing 13 902 two-year risk periods. MEASUREMENTS: ESKD was defined as initiation of dialysis or transplantation. eGFR was calculated using 5 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine and/or cystatin C, with or without race adjustment. The predicted 2-year risk for ESKD was calculated using the 4-variable Kidney Failure Risk Equation (KFRE). We evaluated the prediction performance of eGFR equations and the KFRE score using discrimination and calibration analyses. RESULTS: During a maximum 16 years of follow-up, 856 participants developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of ESKD compared with eGFR alone (area under the curve ranges, 0.945 to 0.954 vs. 0.900 to 0.927). Prediction performance of KFRE scores using different eGFR equations was similar, but the creatinine equation without race adjustment improved calibration among Black participants. Among all participants, compared with an eGFR less than 20 mL/min/1.73 m2, a KFRE score greater than 20% had similar specificity for predicting 2-year ESKD risk (ranges, 0.94 to 0.97 vs. 0.95 to 0.98) but higher sensitivity (ranges, 0.68 to 0.78 vs. 0.42 to 0.66). LIMITATION: Data are solely from the United States. CONCLUSION: The KFRE score better predicts 2-year risk for ESKD compared with eGFR alone, regardless of race adjustment. The creatinine equation with age and sex may improve calibration among Black patients. A KFRE score greater than 20% showed high specificity and sensitivity for predicting 2-year risk for ESKD. PRIMARY FUNDING SOURCE: National Institutes of Health.

Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study.

RATIONALE & OBJECTIVE: Elevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m2. PREDICTOR: Fasting DCA levels in Chronic Renal Insufficiency Cohort study participants. OUTCOMES: Risks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality. ANALYTICAL APPROACH: We used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes. RESULTS: The strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes. LIMITATIONS: We were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels. CONCLUSIONS: In 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.

Predicted cardiovascular risk for United States adults with diabetes, chronic kidney disease, and at least 65 years of age.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline recommends using 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk to guide decisions to initiate antihypertensive medication. METHODS: We included adults aged 40-79 years from the National Health and Nutrition Examination Survey 2013-2018 (n = 8803). We computed 10-year predicted ASCVD risk using the Pooled Cohort risk equations. Clinical CVD was self-reported. Analyses were conducted overall and among those with stage 1 hypertension, defined by a mean SBP of 130-139 mmHg or DBP of 80-89 mmHg. In subgroups defined by diabetes, chronic kidney disease (CKD), and age at least 65 years, we estimated the proportion of United States adults with high ASCVD risk (i.e. 10-year predicted ASCVD risk ≥10% or clinical CVD) and estimated age-adjusted probability of having high ASCVD risk. RESULTS: Among United States adults, an estimated 72.3, 64.5, and 83.9 of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. Among United States adults with stage 1 hypertension, an estimated 55, 36.7, and 72.6% of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. The probability of having high ASCVD risk increased with age and exceeded 50% for United States adults with diabetes and CKD at ages 52 and 57 years, respectively. For those with stage 1 hypertension, these ages were 55 and 64 years, respectively. CONCLUSION: Most United States adults with diabetes, CKD, or age at least 65 years had high ASCVD risk. However, many with stage 1 hypertension did not.

Secular Trends in Cardiovascular Health in US Adults (from NHANES 2007 to 2018).

Deceleration in the decline of cardiovascular disease mortality has been observed recently in the US. We aimed to examine the recent secular trends of cardiovascular health metrics in the US general population. A total of 32,832 adults aged ≥20 years from the National Health and Nutrition Examination Surveys 2007 to 2018 were included in this analysis. Cardiovascular health included 7 health metrics: smoking status, body mass index, physical activity, healthy diet score, total cholesterol, blood pressure, and fasting plasma glucose. Age-standardized mean of overall cardiovascular health score did not significantly change during 2007 to 2010, 2011 to 2014, and 2015 to 2018 in the US adult population (7.88, 8.03, and 7.91, respectively, P-trend = 0.85). The age-standardized proportions of ideal smoking status (P-trend = 0.003), ideal physical activity (P-trend = 0.03), and untreated total cholesterol <200 mg/dL (P-trend <0.001) were significantly increased but the proportions of body mass index <25.0 kg/m2 (P-trend <0.001), systolic/diastolic blood pressure <120/80 mmHg (P-trend = 0.02), and fasting plasma glucose <100 mg/dL (P-trend <0.001) were significantly decreased during the same period of time in the US adults. In conclusion, from 2007 to 2018, overall cardiovascular health did not change in the US general adult population. Of note, body mass index, blood pressure, and fasting plasma glucose significantly worsened during the same period.

Trends in Cardiovascular Risk Factors in US Adults by Race and Ethnicity and Socioeconomic Status, 1999-2018.

Importance: After decades of decline, the US cardiovascular disease mortality rate flattened after 2010, and racial and ethnic differences in cardiovascular disease mortality persisted. Objective: To examine 20-year trends in cardiovascular risk factors in the US population by race and ethnicity and by socioeconomic status. Design, Setting, and Participants: A total of 50 571 participants aged 20 years or older from the 1999-2018 National Health and Nutrition Examination Surveys, a series of cross-sectional surveys in nationally representative samples of the US population, were included. Exposures: Calendar year, race and ethnicity, education, and family income. Main Outcomes and Measures: Age- and sex-adjusted means or proportions of cardiovascular risk factors and estimated 10-year risk of atherosclerotic cardiovascular disease were calculated for each of 10 two-year cycles. Results: The mean age of participants ranged from 49.0 to 51.8 years and the proportion of women from 48.2% to 51.3% in the surveys. From 1999-2000 to 2017-2018, age- and sex-adjusted mean body mass index increased from 28.0 (95% CI, 27.5-28.5) to 29.8 (95% CI, 29.2-30.4); mean hemoglobin A1c increased from 5.4% (95% CI, 5.3%-5.5%) to 5.7% (95% CI, 5.6%-5.7%) (both P < .001 for linear trends). Mean serum total cholesterol decreased from 203.3 mg/dL (95% CI, 200.9-205.8 mg/dL) to 188.5 mg/dL (95% CI, 185.2-191.9 mg/dL); prevalence of smoking decreased from 24.8% (95% CI, 21.8%-27.7%) to 18.1% (95% CI, 15.4%-20.8%) (both P < .001 for linear trends). Mean systolic blood pressure decreased from 123.5 mm Hg (95% CI, 122.2-124.8 mm Hg) in 1999-2000 to 120.5 mm Hg (95% CI, 119.6-121.3 mm Hg) in 2009-2010, then increased to 122.8 mm Hg (95% CI, 121.7-123.8 mm Hg) in 2017-2018 (P < .001 for nonlinear trend). Age- and sex-adjusted 10-year atherosclerotic cardiovascular disease risk decreased from 7.6% (95% CI, 6.9%-8.2%) in 1999-2000 to 6.5% (95% CI, 6.1%-6.8%) in 2011-2012, then did not significantly change. Age- and sex-adjusted body mass index, systolic blood pressure, and hemoglobin A1c were consistently higher, while total cholesterol was lower in non-Hispanic Black participants compared with non-Hispanic White participants (all P < .001 for group differences). Individuals with college or higher education or high family income had consistently lower levels of cardiovascular risk factors. The mean age- and sex-adjusted 10-year risk of atherosclerotic cardiovascular disease was significantly higher in non-Hispanic Black participants compared with non-Hispanic White participants (difference, 1.4% [95% CI, 1.0%-1.7%] in 1999-2008 and 2.0% [95% CI, 1.7%-2.4%] in 2009-2018]). This difference was attenuated (-0.3% [95% CI, -0.6% to 0.1%] in 1999-2008 and 0.7% [95% CI, 0.3%-1.0%] in 2009-2018) after further adjusting for education, income, home ownership, employment, health insurance, and access to health care. Conclusions and Relevance: In this serial cross-sectional survey study that estimated US trends in cardiovascular risk factors from 1999 through 2018, differences in cardiovascular risk factors persisted between Black and White participants; the difference may have been moderated by social determinants of health.