Search

Background: Although practice guidelines stress individualization of glucose management in patients with type 2 diabetes (T2D), the extent to which providers take patient factors into account when selecting medications is not well known.Methods: Diabetes Collaborative Registry (DCR) is an outpatient diabetes registry including primary care, cardiology, and endocrinology practices. T2D medications were grouped as those which may be suboptimal for key patient subgroups, and we examined patient factors associated with use of these agents using hierarchical, multivariable Poisson models.Results: In DCR, 157,551 patients from 374 US practices were prescribed a glucose-lowering medication. Patients with morbid obesity were more likely treated with medications prone to cause weight gain (relative rate [RR] 1.09, 95% CI 1.07-1.11). Older patients were more likely to be treated with medications with increased risk of hypoglycemia (RR 1.04 per 5 years, 95% CI 1.04-1.05). Patients with CKD 4/5 were less likely to be treated with agents with known risk in patients with advanced CKD (RR 0.74, 95% CI 0.71-0.77). Patients with coronary artery disease were no more or less likely to be treated with medications with potential cardiovascular safety issues (RR 0.99, 95% CI 0.96-1.01).Conclusions: We observed some targeted use of glucose-lowering therapies in certain subgroups but also identified potential opportunities for better personalization of treatment. Data sources such as the DCR can highlight potential areas for improving targeted approaches to pharmacologic therapy in order to optimize selection of patients most likely to benefit (and least likely to be harmed) from treatments. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV–B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine. Methods A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. Results Post-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups. Conclusion HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older. [ABSTRACT FROM AUTHOR]

Measurement of glycated hemoglobin (HbA1c), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of HbA1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA1c reduction and cardiovascular disease prevention in patients with diabetes is more complex, with data from large randomized trials published over the past decade providing clear evidence that lowering of HbA1c per se is an inadequate marker for a therapeutic regimen's impact on cardiovascular outcomes and patient survival. Recent revisions in professional society guidelines moved away from uniform recommendations and toward a more nuanced, patient-centered approach to HbA1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA1c contemporary assays and their limitations. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to determine whether there are race and gender differences in the distribution of C-reactive protein (CRP) levels. Background: Few data are available comparing CRP distributions in different race and gender groups. Recent clinical practice recommendations for CRP testing for cardiovascular risk assessment suggest a uniform threshold to define high relative risk (>3 mg/l). Methods: We measured CRP in 2,749 white and black subjects ages 30 to 65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample, and compared levels of CRP between different race and gender groups. Results: Black subjects had higher CRP levels than white subjects (median, 3.0 vs. 2.3 mg/l; p < 0.001) and women had higher CRP levels than men (median, 3.3 vs. 1.8 mg/l; p < 0.001). The sample-weight adjusted proportion of subjects with CRP levels >3 mg/l was 31%, 40%, 51%, and 58% in white men, black men, white women, and black women, respectively (p < 0.05 for each group vs. white men). After adjustment for traditional cardiovascular risk factors, estrogen and statin use, and body mass index, a CRP level >3 mg/l remained more common in white women (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1 to 2.5) and black women (OR 1.7; 95% CI 1.2 to 2.6) but not in black men (OR, 1.3; 95% CI, 0.8 to 1.9) when compared with white men. Conclusions: Significant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups. [Copyright &y& Elsevier]

Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. This study sought to determine the effect of ticagrelor on limb events. Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P interaction = 0.40) or TIMI major bleeding (P interaction = 0.3239). Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795) [Display omitted] [ABSTRACT FROM AUTHOR]

South Asian individuals shoulder a disproportionate burden of cardiometabolic diseases. The purpose of this study was to determine if vascular regenerative cell content varies significantly between South Asian and White European people. Between January 2022 and January 2023, 60 South Asian and 60 White European adults with either documented cardiovascular disease or established diabetes with ≥1 other cardiovascular risk factor were prospectively enrolled. Vascular regenerative cell content in venous blood was enumerated using a flow cytometry assay that is based on high aldehyde dehydrogenase (ALDHhi) activity and cell surface marker phenotyping. The primary outcome was the difference in frequency of circulating ALDHhi progenitor cells, monocytes, and granulocytes between the 2 groups. Compared with White European participants, those of South Asian ethnicity were younger (69 ± 10 years vs 66 ± 9 years; P < 0.05), had lower weight (88 ± 19 kg vs 75 ± 13 kg; P < 0.001), and exhibited a greater prevalence of type 2 diabetes (62% vs 92%). South Asian individuals had markedly lower circulating frequencies of pro-angiogenic ALDHhiSSClowCD133+ progenitor cells (P < 0.001) and ALDHhiSSCmidCD14+CD163+ monocytes with vessel-reparative capacity (P < 0.001), as well as proportionally more ALDHhi progenitor cells with high reactive oxygen species content (P < 0.05). After correction for sex, age, body mass index, and glycated hemoglobin, South Asian ethnicity was independently associated with lower ALDHhiSSClowCD133+ cell count. South Asian people with cardiometabolic disease had less vascular regenerative and reparative cells suggesting compromised vessel repair capabilities that may contribute to the excess vascular risk in this population. (The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion [ORIGINS-RCE]; NCT05253521) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.Objectives: In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors.Methods: Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications.Results: In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications.Conclusion: Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population. [ABSTRACT FROM AUTHOR]

The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease. We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels. We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models. We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58). In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c. [Display omitted] [ABSTRACT FROM AUTHOR]

The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on heart failure (HF) outcomes and cardiovascular (CV) death in patients with varying combinations of type 2 diabetes mellitus (T2DM), HF, and chronic kidney disease (CKD) are uncertain. The authors conducted a meta-analysis assessing the effects of SGLT2 inhibitors on HF outcomes and CV death across different patient populations. Online databases were queried up to November 2022 for primary and secondary analyses of trials of SGLT2 inhibitors in patients with HF, T2DM, or CKD. Outcomes of interest were composite of first heart failure hospitalization (HFH) or CV death (first HFH/CV death), first HFH, and CV death. Data were pooled by means of a random-effects model to derive HRs and 95% CIs. Thirteen trials (n = 90,413) were included. Compared with placebo, SGLT2 inhibitors reduced the risk of first HFH/CV death by 24% in HF (HR: 0.76; 95% CI: 0.72-0.81), 23% in T2DM (HR: 0.77; 95% CI: 0.73-0.81), and 23% in CKD (HR: 0.77; 95% CI: 0.72-0.82). The benefit was consistent in HF with reduced or preserved ejection fraction, HF with or without T2DM, and HF with or without CKD. The benefit was also consistent in T2DM with or without CKD, T2DM without HF, CKD without HF, and in patients with all 3 comorbidities. SGLT2 inhibitors significantly reduced CV death by 16% in HF, 15% in T2DM, and 12% in CKD. SGLT2 inhibitors reduce HF events and CV death in cohorts of HF, T2DM and CKD, and these effects appear consistent in patients with varying combinations of these diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus are at increased risk for macrovascular disease complications. Hyperglycemia and atherosclerotic disease clearly are associated, and biologic intermediates mediated by hyperglycemia exist. Our understanding of the pathobiology linking hyperglycemia and atherosclerotic disease continues to evolve. Modulation of the advanced glycation end product (AGE) receptor for AGE (RAGE)/soluble RAGE (sRAGE) system, the thromboxane receptor, and C-peptide comprise just a few of the plausible links between dysglycemia and atherosclerosis. It seems intuitive, therefore, that therapeutic management of blood glucose in patients with diabetes should reduce macrovascular disease and related deaths. However, studies of glucose-lowering therapies performed to date yield qualitatively and quantitatively different results. No definitive proof of the concept is yet available, although it remains probable, with investigations presently under way. Numerous interventions extending beyond glucose control, including lifestyle modification, pharmacologic therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), aspirin, and angiotensin-converting enzyme inhibitors, as well as aggressive blood pressure control independent of blood pressure levels, have proved to be of cardiovascular benefit in the high-risk population of patients with diabetes. Thus, all of these interventions should be used in addition to glucose management in all patients with diabetes who are at increased risk for cardiovascular disease. [Copyright &y& Elsevier]

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus. These high-risk patients benefit from aggressive risk factor management, with blood pressure and low-density lipoprotein-cholesterol treatment, glycemic control, kidney protection, and lifestyle intervention. There are several recommendation and guideline documents across cardiology, endocrinology, nephrology, and general medicine professional societies from the United States and Europe with recommendations for cardiovascular risk reduction in patients with type 2 diabetes mellitus. Although there are some noteworthy differences, particularly in risk stratification, low-density lipoprotein-cholesterol and blood pressure treatment targets, and the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, overall there is considerable alignment across recommendations from different professional societies. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Most lipoprotein-associated phospholipase A2 (Lp-PLA2) studies included mainly white men. We sought to determine whether Lp-PLA2 levels differ according to race and sex. Methods: Lp-PLA2 mass and activity were measured in 3332 subjects age 30–65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample. Lp-PLA2 levels were compared between different race and sex groups. Results: Mean age was 45±9 years and 44% were men; 30% were white, 17% hispanic, and 53% black. Mean Lp-PLA2 activity and mass were 146±40nmol/min/mL and 191±60ng/mL, respectively. Lp-PLA2 activity was lower in women compared with men (134±35 vs. 161±40, p =0.001) and was lowest in black (136±38), intermediate in hispanic (151±36), and highest in white subjects (161±39) (trend p =0.0001). In multivariable linear regression models, after adjusting for age, body mass index (BMI), smoking, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and high sensitivity C-reactive protein (hsCRP), Lp-PLA2 activity was 19nmol/min/mL higher in men vs. women (p <0.001); compared with black subjects, adjusted Lp-PLA2 activity was 11 and 20nmol/min/mL higher in white and hispanic subjects, respectively (both p <0.001). Similar race and sex differences were observed for Lp-PLA2 mass. Conclusion: Race and sex independently influence Lp-PLA2 activity and mass. Thresholds to define Lp-PLA2 elevation may need to be sex and race specific. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. Background: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. Methods: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. Results: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). Conclusions: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden. [Copyright &y& Elsevier]

Abstract: Background: Whether the absence of coronary artery calcium, or conversely the presence of high volumes of coronary artery calcium, may alter assessment of coronary heart disease risk based on traditional risk factors is uncertain. We sought to identify a potential threshold of coronary artery calcium for clinical use and examine the predictive power of coronary artery calcium in individuals categorized using conventional coronary heart disease risk assessment. Methods: The study included 10,746 men and women (36.3%) with a mean age of 53.8±9.9 years who were either physician- or self-referred for electron beam tomography scanning to a preventive medical clinic. Coronary heart disease risk factors were elicited by use of a questionnaire. Results: During a mean follow-up of 3.5 years, 81 primary events (coronary heart disease death or nonfatal myocardial infarction) occurred. Among individuals with a coronary artery calcium score of zero, the primary event rate was very low (0.4 events per 1000 person-years of observation). When participants were stratified by self-reported coronary heart disease risk factors (0–2, or 3–4), a coronary artery calcium score ≥100 was associated with substantially increased risk of coronary heart disease events within each level of stratification. In a subgroup of participants with available clinical data, similar results were found when participants were categorized by Framingham risk scores. Conclusions: Coronary artery calcium score can identify individuals at increased risk for coronary heart disease events who otherwise would be considered low-risk based on clinical assessment. A coronary artery calcium score of zero is associated with very low risk for coronary heart disease in the short to intermediate term (≈3.5 years) regardless of the number of risk factors present. [Copyright &y& Elsevier]

Patients who have diabetes mellitus have 2 times the incidence of an acute coronary syndrome (ACS) and 2 times the mortality rate after ACS compared with patients who do not have diabetes. Poor patient understanding of diabetes is believed to impede appropriate self-management, thus accelerating cardiovascular complications. We investigated the relation between patients'' diabetes-related knowledge (DRK) and measurements of risk factor control and cardiac outcomes. Two hundred patients who had diabetes mellitus and ACS and were admitted to a university hospital were enrolled over a 9-month period. At enrollment, clinical and demographic data were recorded, and each patient completed a previously validated DRK assessment. Clinical outcomes data were obtained 6 months after enrollment. Years of education and DRK assessment score were moderately correlated (r = 0.496, p &#60;0.0001). Glycosylated hemoglobin, low-density lipoprotein cholesterol, and body mass index showed no correlation with DRK assessment score (r = −0.045, −0.005, and 0.175, respectively), even after multivariable adjustment for differences in age, race, insulin requirement, duration of diabetes, and years of education. Rates of 6-month death (6.2% vs 9.7%) and death or myocardial infarction (15.5% vs 19.4%) were not significantly different between groups of patients stratified by DRK assessment scores (high vs low scoring groups). Thus, among patients who have diabetes and ACS, there is a moderate correlation between years of education and DRK. We found no correlation between DRK and measurements of risk factor control or 6-month clinical outcomes. New strategies must be developed to translate understanding of disease into better risk factor modification among patients who have diabetes and ACS. [Copyright &y& Elsevier]

We sought to evaluate the association between plasma levels of monocyte chemoattractant protein (MCP)-1 and the risk for subclinical atherosclerosis.Monocyte chemoattractant protein is a chemokine that recruits monocytes into the developing atheroma and may contribute to atherosclerotic disease development and progression. Plasma levels of MCP-1 are independently associated with prognosis in patients with acute coronary syndromes, but few population-based data are available from subjects in earlier stages of atherosclerosis.In the Dallas Heart Study, a population-based probability sample of adults in Dallas County ≤65 years old, plasma levels of MCP-1 were measured in 3,499 subjects and correlated with traditional cardiovascular risk factors, high-sensitivityC-reactive protein (hs-CRP), and coronary artery calcium (CAC) measured by electron beam computed tomography.Higher MCP-1 levels were associated with older age, white race, family history of premature coronary disease, smoking, hypertension, diabetes, hypercholesterolemia, and higher levels of hs-CRP (p < 0.01 for each). Similar associations were observed between MCP-1 and risk factors in the subgroup of participants without detectable CAC. Compared with the subjects in the lowest quartile of MCP-1, the odds of prevalent CAC (CAC score ≥10) for subjects in the second, third, and fourth quartiles were 1.30 (95% confidence interval [CI] 0.99 to 1.73), 1.60 (95% CI 1.22 to 2.11), and 2.02 (95% CI 1.54 to 2.63), respectively. The association between MCP-1 and CAC remained significant when adjusted for traditional cardiovascular risk factors, but not when further adjusted for age.In a large population-based sample, plasma levels of MCP-1 were associated with traditional risk factors for atherosclerosis, supporting the hypothesis that MCP-1 may mediate some of the atherogenic effects of these risk factors. These findings support the potential role of MCP-1 as a biomarker target for drug development. [Copyright &y& Elsevier]

We sought to compare the prevalence of coronary atherosclerosis in a cohort of middle-age African American (black) and non-Hispanic Caucasian (white) men and women from a population-based probability sample.Blacks have a higher mortality from coronary heart disease (CHD) than whites, particularly among younger individuals, and yet several studies have reported that coronary atherosclerosis is less prevalent in blacks than in whites. Data from population-based samples comparing coronary atherosclerotic burden between blacks and whites are limited.The prevalence of coronary atherosclerosis in middle-aged blacks and whites was determined using coronary calcium measured by electron beam computed tomography in 1,289 men and women from a population-based probability sample from Dallas, Texas.The population estimates of the frequency of a positive scan for coronary artery calcium were not statistically different between black and white men (37% vs. 41%, p = 0.36) or between black and white women (29% vs. 23%, p = 0.21). Although the prevalence of most of the coronary risk factors varied significantly between blacks and whites, mean Framingham coronary risk factor scores were identical in black and white men (10 ± 4) but significantly higher in black women (13 ± 4) than in white women (12 ± 4).Blacks in the general population have a prevalence of coronary atherosclerosis similar to whites. Factors other than coronary atherosclerotic burden, which are not reflected in the Framingham risk score, contribute significantly to the higher CHD mortality rate in blacks. [Copyright &y& Elsevier]

Background: Diabetes is associated with abnormalities in cardiac remodeling and high risk of heart failure (HF).Objectives: The purpose of this study was to evaluate the prevalence and prognostic implications of diabetes with cardiomyopathy (DbCM) among community-dwelling individuals.Methods: Adults without prevalent cardiovascular disease or HF were pooled from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], CHS [Cardiovascular Health Study], CRIC [Chronic Renal Insufficiency Cohort]). Among participants with diabetes, DbCM was defined using different definitions: 1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); 2) intermediate restrictive: ≥2 echocardiographic abnormalities; and 3) most restrictive: elevated N-terminal pro-B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities. Adjusted Fine-Gray models were used to evaluate the risk of HF.Results: Among individuals with diabetes (2,900 of 10,208 included), the prevalence of DbCM ranged from 67.0% to 11.7% in the least and most restrictive criteria, respectively. Higher fasting glucose, body mass index, and age as well as worse kidney function were associated with higher risk of DbCM. The 5-year incidence of HF among participants with DbCM ranged from 8.4%-12.8% in the least and most restrictive definitions, respectively. Compared with euglycemia, DbCM was significantly associated with higher risk of incident HF with the highest risk observed for the most restrictive definition of DbCM (HR: 2.55 [95% CI: 1.69-3.86]; least restrictive criteria HR: 1.99 [95% CI: 1.50-2.65]). A similar pattern of results was observed across cohort studies, across sex and race subgroups, and among participants without hypertension or obesity.Conclusions: Regardless of the criteria used to define cardiomyopathy, DbCM identifies a high-risk subgroup for developing HF. [ABSTRACT FROM AUTHOR]

We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). TECOS participants with a history of AF were stratified by CHA 2 DS 2 -VASc score and their antithrombotic use evaluated. Cox proportional hazards models were employed to explore possible associations between history of AF and prespecified clinical outcomes after adjusting for key baseline characteristics. Of the 14,671 TECOS participants, 1167 (8%) had a history of AF, of whom 51.6% were using vitamin K antagonists (VKA); 31.2% used VKA alone, 16.9% used aspirin plus VKA, 1.8% used clopidogrel plus VKA, and 1.7% used aspirin and clopidogrel plus VKA. Aspirin was used by 56.8%: 30.9% used aspirin alone and 7.3% aspirin plus clopidogrel. Clopidogrel alone was used by 2.9%, and 7.3% were not using any antithrombotic medication. Participants with a history of AF had a higher risk of cardiovascular events, including hospitalization for heart failure and all-cause mortality, than those without AF. White, older men with prior myocardial infarction, heart failure, peripheral artery disease, or prior stroke were more likely to develop new-onset AF than others without these characteristics. Almost half of high-risk AF patients with diabetes and established ASCVD in TECOS were not treated with anticoagulation therapy despite clear guideline recommendations for such therapy, highlighting the challenge and potential for clinical improvements in managing these patients in clinical practice. Clinical Trial Registration : URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205. • Afib and type 2 diabetes are associated with adverse cardiovascular outcomes. • We examined OAC use by TECOS patients with Afib, ASCVD, and type 2 diabetes. • OAC use by these high-risk patients is much less than guideline recommendations. [ABSTRACT FROM AUTHOR]

Despite multiple examples of glucose-lowering therapies affecting heart failure (HF) risk, ascertainment of HF data in cardiovascular outcome trials of these medications has not been systematically characterized. In this review, large (n >1,000) published phase III and IV cardiovascular outcome trials evaluating glucose-lowering therapies through June 2017 were identified. Data were abstracted from publications, U.S. Food and Drug Administration advisory committee records, and U.S. Food and Drug Administration labeling documents. Overall, 21 trials including 152,737 patients were evaluated. Rates and definitions of baseline HF and incident HF were inconsistently provided. Baseline ejection fraction data were provided in 3 studies but not specific to patients with HF. No trial reported functional class, ejection fraction, or HF therapy at the time of incident HF diagnosis. HF hospitalization data were available in 15 trials, but only 2 included HF-related events within the primary composite endpoint. This systematic review highlights gaps in HF data capture within cardiovascular outcome trials of glucose-lowering therapies and outlines rationale and strategies for improving HF characterization. [ABSTRACT FROM AUTHOR]

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and when and how to implement medical therapies. These recommendations are organized into primary and secondary prevention along the continuum from obesity through the metabolic syndrome, prediabetes, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation, chronic kidney disease (CKD), and heart failure (HF). The goal of early and intensive intervention is primary prevention of comorbidities or secondary prevention to decrease further worsening of disease and reduce morbidity and mortality. These efforts will reduce clinical inertia and may improve patients' well-being and adherence. • Diabetes, obesity and cardiorenal/metabolic disease often occur in the same patient. • Suboptimal metabolic control has not improved in past 20 years despite new medications. • Traditional, stepwise treatment often leads to inertia and morbidity and mortality. • Early intensive combination intervention can prevent disease progression and events. • Recommendations cover early intervention in both primary and secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Multiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States.Objectives: The goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, ≥140/90 mm Hg; normal home BP, <135/85 mm Hg), MH (high home BP, ≥135/85 mm Hg; normal clinic BP, <140/90 mm Hg), and sustained hypertension (high home and clinic BP) in the DHS (Dallas Heart Study), a large, multiethnic, probability-based population cohort.Methods: Associations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed.Results: The study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors.Conclusions: In a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults. [ABSTRACT FROM AUTHOR]

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probabilitybased, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94,95% CI 0.78 to 1.13, Pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (Pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. Objectives This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Methods Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Results Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m 2 ), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Conclusions Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts. Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race. Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold. Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay. [ABSTRACT FROM AUTHOR]

Intensive statin therapy is a central component of secondary prevention after acute myocardial infarction (AMI), particularly among high-risk patients, such as those with diabetes mellitus (DM). However, the frequency and predictors of intensive statin therapy use after AMI among patients withDMhave not been described. We examined patterns of intensive statin therapy use (defined as a statin with expected low-density lipoprotein cholesterol lowering of >50%) at discharge among patientswithAMIwithknownDMenrolled in a 24-siteUSregistry. Predictors of intensive statin therapy use were evaluated using multivariable hierarchical Poisson regression models. Among 1,300 patients with DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge. Inmultivariablemodels, ST-elevationAMI (risk ratio [RR] 1.48, 95% confidence interval [CI] 1.29 to 1.70), insurance for medications (RR 1.28, 95% CI 1.00 to 1.63), and higher low-density lipoprotein cholesterol levels (RR1.05 per 1mg/dl, 95%CI 1.02 to 1.07) were independent predictors of intensive statin therapy, whereas higher Global Registry of Acute Coronary Events scores were associated with lower rates of intensive statin therapy (RR0.94 per 10 points, 95%CI 0.91 to 0.98). In conclusion, only 1 in 5 patients withDM was prescribed intensive statin therapy at discharge after an AMI. Predictors of intensive statin therapy use suggest important opportunities to improve quality of care in this patient population. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background: Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. Methods: A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results: Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = −0.08; p < 0.0001) and liver fat (beta coefficient = −0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions: Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. [Copyright &y& Elsevier]

Objectives: This study sought to examine the reliability and prognostic importance of an in-hospital diagnosis of metabolic syndrome (MetS) in the setting of acute myocardial infarction (AMI). Background: Because the factors that comprise MetS are believed to be altered in the setting of AMI, the diagnosis of MetS during AMI hospitalization and its prognostic significance have not been studied. Methods: We assessed patients within a multicenter registry for metabolic factors at baseline and 1 month post-AMI and followed them for mortality and rehospitalizations. The accuracy of an inpatient diagnosis of MetS was calculated using a 1-month follow-up as the gold standard. Patients were categorized based on MetS diagnosis at baseline and 1 month, and the combined endpoint of death or rehospitalization over 12 months was compared between groups. Results: Of the 1,129 patients hospitalized for AMI, diagnostic criteria for MetS were met by 69% during AMI hospitalization and 63% at 1 month. Inpatient MetS diagnosis had a sensitivity and specificity for outpatient diagnosis of 87% and 61%, respectively, and was associated with an 11 times increased odds of an outpatient diagnosis (C-index 0.74). Compared with patients without MetS during hospitalization and follow-up, patients classified as MetS during AMI but not follow-up had worse outcomes, whereas those classified MetS at follow-up had the worst outcomes (rates for combined endpoint 27% vs. 37% vs. 38%; log-rank p = 0.01). Conclusions: In a large cohort of patients with AMI, the diagnosis of MetS is common and can be made with reasonable accuracy during AMI. MetS is associated with poor outcomes, regardless of whether the diagnosis is confirmed during subsequent outpatient visit, and identifies a high-risk cohort of patients that may benefit from more aggressive risk factor modification. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359) [Copyright &y& Elsevier]

Women with angina pectoris and abnormal stress test findings commonly have no epicardial coronary artery disease (CAD) at catheterization. The aim of the present study was to develop a risk score to predict obstructive CAD in such patients. Data were analyzed from 337 consecutive women with angina pectoris and abnormal stress test findings who underwent cardiac catheterization at our center from 2003 to 2007. Forward selection multivariate logistic regression analysis was used to identify the independent predictors of CAD, defined by ‡50% diameter stenosis in ‡1 epicardial coronary artery. The independent predictors included age ‡55 years (odds ratio 2.3, 95% confidence interval 1.3 to 4.0), body mass index <30 kg/m2 (odds ratio 1.9, 95% confidence interval 1.1 to 3.1), smoking (odds ratio 2.6, 95% confidence interval 1.4 to 4.8), low high-density lipoprotein cholesterol (odds ratio 2.9, 95% confidence interval 1.5 to 5.5), family history of premature CAD (odds ratio 2.4, 95% confidence interval 1.0 to 5.7), lateral abnormality on stress imaging (odds ratio 2.8, 95% confidence interval 1.5 to 5.5), and exercise capacity <5 metabolic equivalents (odds ratio 2.4, 95% confidence interval 1.1 to 5.6). Assigning each variable 1 point summed to constitute a risk score, a graded association between the score and prevalent CAD (ptrend <0.001). The risk score demonstrated good discrimination with a cross-validated c-statistic of 0.745 (95% confidence interval 0.70 to 0.79), and an optimized cutpoint of a score of £2 included 62% of the subjects and had a negative predictive value of 80%. In conclusion, a simple clinical risk score of 7 characteristics can help differentiate those more or less likely to have CAD among women with angina pectoris and abnormal stress test findings. This tool, if validated, could help to guide testing strategies in women with angina pectoris. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at higher risk for heart failure (HF) and death. Background: The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) on cardiovascular (CV) outcomes in the general population is unknown. Methods: Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by magnetic resonance imaging (MRI), cTnT by highly sensitive assay, and NT-proBNP analysis (n = 2,413). Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (–) of LVH and biomarker levels above (+) or below (–) the predefined threshold. Results: Nine percent of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker– (p < 0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH– cTnT–), 4% (LVH– cTnT+), and 6% (LVH+ cTnT–) (p < 0.0001). The interactions between LVH and cTnT (pinteraction = 0.0005) and LVH and NT-proBNP (pinteraction = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH– biomarker–. Conclusions: Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate whether the relationship between C-reactive protein (CRP) and atherosclerosis is modified by body mass index (BMI). Background: CRP levels are affected by obesity, and it is unknown whether the associations between CRP and cardiovascular (CV) disease differ between obese and nonobese individuals. Methods: We measured CRP and multiple atherosclerosis phenotypes, including coronary artery calcification (CAC) (n = 2,685), aortic wall thickness (AWT) (n = 2,238), and aortic plaque burden (APB) (n = 2,224), in subjects ages 30 to 65 years from the Dallas Heart Study. The associations of CRP with CAC, AWT, and APB were compared across categories of BMI (normal, 18.5 to <25 kg/m2; overweight, 25 to <30 kg/m2; obese, ≥30 kg/m2) in sex-stratified analyses. Results: The overall prevalence of obesity was 38% in men and 53% in women. Increasing CRP levels (<1 mg/l, 1 to 3 mg/l, >3 mg/l) were associated with increased CAC prevalence in normal and overweight men and in normal weight women (p < 0.01), but not in obese subjects of either sex. Likewise, the correlations between CRP and AWT and APB diminished with increasing BMI and were nonsignificant in obese individuals (p < 0.05 in nonobese, p > 0.1 in obese). Interaction tests between CRP and obesity were significant for all atherosclerosis measures in men and for AWT and ABP in women (p interaction <0.05 each). In both sexes, the c-statistics of CRP for all 3 atherosclerosis measures were greater for normal weight than obese individuals. Conclusions: In a large, population-based study, the association between CRP and multiple measures of atherosclerosis is diminished in obese individuals. The role of CRP for predicting CV outcomes in obese subjects requires further evaluation. [ABSTRACT FROM AUTHOR]