Search

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-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, 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 cardiac troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. CONCLUSIONS: Because myocardial infarction is rare in adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile URLs might be considered to define pediatric myocardial injury.

BackgroundThe prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population.MethodsWe 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.ResultsThe 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 (ConclusionsAmong 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.

Purpose of Review The treatment of hypertension has changed dramatically over the last century, with recent trials informing clinical guidelines that recommend aiming for lower blood pressure (BP) targets than ever before. However, a “J”- or “U-shaped curve” in the association between diastolic BP and cardiovascular events has been observed in epidemiological studies, suggesting that both high diastolic BPs and diastolic BPs below a certain nadir are associated with higher risk of cardiovascular disease (CVD) events. Despite the potential for confounding and reverse causation, this association may caution against overly intensive BP lowering in some hypertensive adults who also have a low baseline diastolic BP. Recent Findings Recent post-hoc analyses of the landmark Systolic Blood Pressure Intervention Trial (SPRINT) appear to contradict these J-curve concerns, finding that the benefit of more intensive BP treatment did not differ based on baseline blood pressure. Similarly, sensitivity analyses of The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized controlled trial found that patients experienced similar benefits from an intensive BP goal, regardless of whether their diastolic BP was above or below 60 mm Hg. Finally, several Mendelian randomization analyses, which are less susceptible to confounding and reverse causation, demonstrated a clear linear relationship between diastolic BP and cardiovascular events. These studies indicate that a potential reduction in CVD risk is possible, irrespective of baseline diastolic BP values. Summary Sufficient recent evidence indicates that low diastolic BP is not causal of worse cardiovascular outcomes but rather represents confounding or reverse causation. Therefore, while low diastolic BP can be considered a marker of CVD risk, this risk is not expected to increase with further BP lowering when necessary to control concomitant elevations of systolic BP. Indeed, BP reduction in this setting appears beneficial.

BACKGROUND The risk of developing hypertension in young adults and its relationship to modifiable lifestyle factors are unclear. We aimed to examine the association of cardiovascular health (CVH) metrics with the risk of hypertension. METHODS We analyzed 66,876 participants aged 20–39 years, with available blood pressure (BP) data for 5 consecutive years, who had normal or elevated BP at the initial health check-up, enrolled in the JMDC Claims Database. Ideal CVH metrics included nonsmoking, body mass index RESULTS The median age was 35 years, and 62% were men. Number of non-ideal CVH metrics was associated with an increasing risk for the development of stage 1 and stage 2 hypertension. Non-ideal body mass index was most strongly associated with a risk for hypertension. This association was more pronounced in women. An annual increase in the number of non-ideal CVH metrics was associated with an elevated risk for the hypertension development. CONCLUSIONS CVH metrics can stratify the risk for hypertension in non-hypertensive adults aged 20–39 years. These findings have important public health implications for the screening and prevention of hypertension. Improving CVH metrics may prevent the risk of developing hypertension in young adults.

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the “obesity paradox”, possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the “obesity paradox” following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD.

Background: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. Objectives: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG. Methods: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality. Results: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without. Conclusions: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Although there is a significant reduction in atherosclerotic cardiovascular disease risk with statins, a higher risk of diabetes mellitus has been demonstrated in randomized clinical trials. The risk of incident diabetes with statins may be heterogeneous by presence of coronary artery calcium (CAC). We evaluated participants without prevalent diabetes at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of subjects free of clinical cardiovascular disease at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between statin use and incident diabetes, adjusting for sociodemographic and cardiovascular risk factors, including time-varying statin use and stratifying by baseline CAC (0, 1 to 100, ≥100). The study population included 5,943 participants with a mean (SD) age of 62 (10) years, 54% women, 41% White, 26% Black, 12% Chinese-American, and 21% Hispanic. In the unadjusted analyses, statin use was associated with a higher risk of incident diabetes (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.27 to 2.06). After adjustment, this risk was no longer significant (HR 1.13, 95% CI 0.83 to 1.54). Although imprecise, the HR expressing the association of statins with diabetes was lower for those with CAC = 0 (HR 0.80, 95% CI 0.45 to 1.40) than for those with a higher CAC burden (HR 1.30, 95% CI 0.71 to 2.39 for CAC 1 to 100 and HR 1.39, 95% CI 0.85 to 2.28 for CAC ≥100), but this heterogeneity was not statistically significant. In conclusion, statin therapy was not significantly associated with incident diabetes mellitus in this observational study. The risk of incident diabetes did not significantly differ by baseline CAC.

Introduction General practice has a key role in diagnosing patients with valvular heart disease (VHD) and referring them to appropriate services. Methods An anonymous survey was conducted to assess the knowledge and clinical practice behaviour of Irish general practitioners (GPs) in relation to VHD. In addition to demographic data, the survey captured information in the following domains: knowledge of VHD prevalence, knowledge of contemporary VHD treatments, barriers to diagnosis, and referral patterns. To augment responses, a monetary prize (donated to charity) was offered and the survey was also disseminated using social media and by the Irish College of General Practitioners. Results Valid survey responses were received from 197 GPs. The sample was well-balanced by gender, number of years in practice, and practice setting. A small proportion of GPs (16.8%) used a stethoscope to examine for VHD in all patients over 60 years, a figure that rose to 22.3% in patients over 75. Approximately half of participants (48%) felt confident in their ability to detect and diagnose VHD using a stethoscope, and 74% felt lack of access to echocardiography was a major barrier to making a VHD diagnosis. There was a high level of awareness among GPs of minimally invasive nonsurgical interventions now available for VHD treatment. Discussion Irish GPs displayed good understanding of contemporary VHD treatment options but reported low confidence and inconsistent practices in evaluating patients for VHD. Improved access to echocardiography might help address these deficiencies, but reorganisation of services will be required in a resource-limited public health service. Graphical abstract

Background: Recent clinical guidelines support intensive blood pressure treatment targets. However, observational data suggest that excessive diastolic blood pressure (DBP) lowering might increase the risk of myocardial infarction (MI), reflecting a J- or U-shaped relationship. Methods: We analyzed 47 407 participants from 5 cohorts (median age, 60 years). First, to corroborate previous observational analyses, we used traditional statistical methods to test the shape of association between DBP and cardiovascular disease (CVD). Second, we created polygenic risk scores of DBP and systolic blood pressure and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel nonlinear MR approaches, we evaluated for nonlinearity in the genetic relationship between DBP and CVD events. Comprehensive MR interrogation of DBP required us to also model systolic blood pressure, given that the 2 are strongly correlated. Results: Traditional observational analysis of our cohorts suggested a J-shaped association between DBP and MI. By contrast, linear MR analyses demonstrated an adverse effect of increasing DBP increments on CVD outcomes, including MI (MI hazard ratio, 1.07 per unit mm Hg increase in DBP; P Conclusions: In this analysis of the genetic effect of DBP, we found no evidence for a nonlinear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.

Background Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk. Objectives This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories. Methods Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors. Results There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to Conclusions Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

Aspirin’s antithrombotic effects have a long-established place in the prevention of cardiovascular disease (CVD), and its traditional use as a core therapy for secondary prevention of CVD is well recognized. However, with the advent of newer antiplatelet agents and an increasing understanding of aspirin’s bleeding risks, its role across the full spectrum of modern CVD prevention has become less certain. As a consequence, recent trials have begun investigating aspirin-free strategies in secondary prevention. For example, a contemporary metanalysis of trials that assessed P2Y12 inhibitor monotherapy versus prolonged (≥ 12 months) dual antiplatelet therapy (which includes aspirin) after percutaneous coronary intervention reported a lower risk of major bleeding and no increase in stent thrombosis, all-cause mortality, myocardial infarction (MI), or stroke in the P2Y12 monotherapy group. In contrast to secondary prevention, aspirin’s role in primary prevention has always been more controversial. While historical trials reported a reduction in MI and stroke, more contemporary trials have suggested diminishing benefit for aspirin in this setting, with no reduction in hard outcomes, and some primary prevention trials have even indicated a potential for harm. In this review, we discuss how changing population demographics, enhanced control of lipids and blood pressure, changes in the definition of outcomes like MI, evolution of aspirin formulations, and updated clinical practice guidelines have all impacted the use of aspirin for primary and secondary CVD prevention.

Background Growing literature linking unconventional natural gas development (UNGD) to adverse health has implicated air pollution and stress pathways. Persons with heart failure (HF) are susceptible to these stressors. Objectives This study sought to evaluate associations between UNGD activity and hospitalization among HF patients, stratified by both ejection fraction (EF) status (reduced [HFrEF], preserved [HFpEF], not classifiable) and HF severity. Methods We evaluated the odds of hospitalization among patients with HF seen at Geisinger from 2008 to 2015 using electronic health records. We assigned metrics of UNGD activity by phase (pad preparation, drilling, stimulation, and production) 30 days before hospitalization or a frequency-matched control selection date. We assigned phenotype status using a validated algorithm. Results We identified 9,054 patients with HF with 5,839 hospitalizations (mean age 71.1 ± 12.7 years; 47.7% female). Comparing 4th to 1st quartiles, adjusted odds ratios (95% confidence interval) for hospitalization were 1.70 (1.35 to 2.13), 0.97 (0.75 to 1.27), 1.80 (1.35 to 2.40), and 1.62 (1.07 to 2.45) for pad preparation, drilling, stimulation, and production metrics, respectively. We did not find effect modification by HFrEF or HFpEF status. Associations of most UNGD metrics with hospitalization were stronger among those with more severe HF at baseline. Conclusions Three of 4 phases of UNGD activity were associated with hospitalization for HF in a large sample of patients with HF in an area of active UNGD, with similar findings by HFrEF versus HFpEF status. Older patients with HF seem particularly vulnerable to adverse health impacts from UNGD activity.

OBJECTIVE: Observational data suggest a potential for subclinical cardiac damage from intensive blood glucose or blood pressure (BP) control, particularly in adults with very low blood glucose and BP levels. However, this has not been tested in a randomized trial. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Research Controlled Evaluation (ADVANCE) study was a factorial, randomized trial designed to test the effects of intensive blood glucose (hemoglobin A1c ≤6.5% versus usual care) and intensive BP (combination of perindopril-indapamide versus placebo) control on vascular events in adults with diabetes. Using mixed effects tobit models, we determined the effect of the randomized interventions on change in subclinical cardiac injury (high sensitivity cardiac troponin T [hs-cTnT]) and strain (N-terminal b-type pro natriuretic peptide [NT-proBNP]), 1 year after randomization. RESULTS: Among the 682 participants, mean age was 66.1 (SD, 6.5) years; 40% were women. Mean baseline hemoglobin A1c was 7.4% (SD, 1.5) and systolic/diastolic BP was 147 (SD,21)/81 (SD,11) mmHg. After 1 year, intensive versus standard glucose control did not significantly change hs-cTnT (1.5%; 95%CI:−4.9,8.2) or NT-proBNP (−10.3%; 95%CI: −20.2%,0.9%). Intensive versus standard BP control also did not affect hs-cTnT (−2.9%; 95%CI: −8.9,3.6), but did significantly lower NT-proBNP by 21.6% (95%CI: −30.2%,−11.9%). Changes in systolic BP at 1 year (versus baseline) were strongly associated with NT-proBNP (P = 0.004), but not hs-cTnT (P = 0.95). CONCLUSIONS: In adults with diabetes, intensive BP control reduced NT-proBNP without increasing hs-cTnT, supporting the benefits and safety of intensive BP control in adults with diabetes. This trial is registered at clinicaltrials.gov, number: NCT00145925.

Aims To evaluate the impact of various smoking status on 10-year all-cause mortality and to examine a relative treatment benefit of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) according to smoking habits. Methods and results The SYNTAX Extended Survival study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to CABG or PCI in the SYNTAX trial. In the present analysis, patients were divided into three groups (current, former, or never smokers), and the primary endpoint of 10-year all-cause mortality was assessed according to smoking status. Smoking status was available in 1793 (99.6%) patients at the time of randomization, of whom 363 were current smokers, 798 were former smokers, and 632 were never smokers. The crude rates of 10-year all-cause mortality were 29.7% in current smokers, 25.3% in former smokers, and 25.9% in never smokers (Log-rank P = 0.343). After adjustment for imbalances in baseline characteristics, current smokers had a significantly higher risk of 10-year all-cause mortality than never smokers [adjusted hazard ratio (aHR): 2.29; 95% confidence interval (CI): 1.60–3.27; P Conclusion Current smokers had a higher adjusted risk of 10-year all-cause mortality, whereas former smokers did not. The treatment effect of CABG vs. PCI did not differ significantly according to smoking status. Clinical trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972; SYNTAX Extended Survival. ClinicalTrials.gov reference: NCT03417050.

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal 100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT10 for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines.

There is a wage gap among men and women practicing cardiology. Differences in industry funding can be both a consequence of and a contributor to gender differences in salaries. We sought to determine whether gender differences exist in the distribution, types, and amounts of industry payments among men and women in cardiology.In this cross-sectional analysis, we used the Centers for MedicareMedicaid Services Open Payment program database to obtain 2016 industry payment data for US cardiologists. We also used UK Disclosure data to obtain 2016 industry payments to UK cardiologists. Outcomes included the proportions of male and female cardiologists receiving industry funding and the mean industry payment amounts received by male and female cardiologists. Where possible, we also assessed 2014 and 2015 data in both locations.Of the 22,848 practicing Centers for MedicareMedicaid Services US cardiologists in 2016, 20,037 (88%) were men and 2,811 (12%) were women. Proportionally more men than women received industry payments in 2016 (78.0% vs 68.5%, respectively; P .001). Men received higher overall mean industry payments than women ($6,193.25 vs. $2,501.55, P .001). Results were similar in 2014 and 2015. Among UK cardiologists, more men (24.4%) than women (13.5%) received industry payments in 2016 (P .001). However, although the difference in overall industry payments was numerically larger among men compared to women, this did not achieve statistical significance (£2,348.31 vs £1,501.37, respectively, P = .35).Industry payments to cardiologists are common, and there are gender differences in these payments on both sides of the Atlantic.

Background Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. Methods We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. Results The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (β-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (β: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. Conclusions Smoking is independently associated with significantly increased oxidative stress as measured by GGT level. This association demonstrates effect modification by NAFLD status, suggesting that smoking may intensify CV risk in individuals with NAFLD.

AIM: We evaluated the associations of two biomarkers of hyperglycemia—hemoglobin A1c(HbA1c) and glycated albumin—with lower extremity disease in US adults overall and by diabetes status. METHODS: We conducted a cross-sectional study of adult participants aged ≥40 years who attended the National Health and Nutrition Examination Survey(NHANES) 1999–2004 (unweighted N=5,785). We used logistic regression to evaluate the associations of HbA1c and glycated albumin with lower extremity disease: peripheral neuropathy (assessed by monofilament test), peripheral artery disease (assessed by ankle-brachial index), history of foot ulcer, or amputation. All analyses were weighted and accounted for the complex NHANES sample survey design. RESULTS: The prevalence of lower extremity disease was 17.4% (15.9% in adults without diabetes and 33.2% in adults with diabetes). HbA1c and glycated albumin were not significantly associated with lower extremity disease in adults without diabetes. However, we observed significant associations of both HbA1c (OR 1.19 per 1-% point increase, 95%CI 1.06–1.34) and glycated albumin (OR 1.06 per 1-% point increase, 95%CI 1.02–1.10) with lower extremity disease in adults with diabetes after adjustment. The patterns of association were similar for HbA1c and glycated albumin (P-for-seemingly-unrelated-regression=0.60), with strong linear associations observed at high (diabetic) levels of both biomarkers. CONCLUSIONS: Our study suggests the importance of diabetes prevention and glycemic control in adults with diabetes to reduce the burden of lower extremity disease.

Background: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear. Methods: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/ Results: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP Conclusions: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.