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BACKGROUND: There is significant heterogeneity in cardiovascular disease (CVD) risk among patients with diabetes mellitus (DM). OBJECTIVES: The purpose of this study was to develop risk scores for total CVD and its components from a contemporary pooled, observational cohort of U.S. adults with DM. METHODS: CVD-free adults with DM aged 40 to 79 years were pooled from 4 U.S. population-based cohorts (CARDIA [Coronary Artery Risk Development in Young Adults], Framingham Offspring, Jackson Heart Study, and the MESA (Multiethnic Study of Atherosclerosis) studied since 2000. Baseline DM-specific and non-DM-specific CVD risk factors were evaluated as predictors. We developed 10-year DM Risk Scores (DMRS) for total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), heart failure (HF) and stroke. Score performance was validated internally and externally. RESULTS: We included 2,174 adults with DM mean age 59.2 ± 10.5 years, 55.4% female and 47.5% Black followed up to 10 years. Age, sex, HbA1c, creatinine, systolic blood pressure, DM medication, and smoking were the most important predictors. The DMRS had good internal discrimination (c-statistics 0.72, 0.72, 0.72, 0.79 and 0.73 for CVD, ASCVD, CHD, HF, and stroke) and calibration (calibration slopes 0.93, 0.95, 0.93, 0.98, and 0.89 for CVD, ASCVD, CHD, HF, and stroke; Greenwood Nam-DAgostino calibration tests were significant for CHD (P

BACKGROUND: Anemia is associated with increased mortality in patients undergoing transcatheter aortic valve replacement (TAVR); however, data on the effect of the severity of and recovery from anemia on clinical outcomes are limited. This study examined the impact of the severity of and recovery from anemia after TAVR. METHODS: Patients with symptomatic, severe aortic stenosis across all surgical risk groups from the Placement of Aortic Transcatheter Valves (PARTNER) I, II, and III trials and registries who underwent TAVR were analyzed. Baseline anemia was defined as mild (hemoglobin [Hb] level ≥11.0 g/dL and

BackgroundCoronary artery calcium (CAC) density is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD) risk. We examined this relation in those with diabetes mellitus (DM) or metabolic syndrome (MetS).MethodsWe studied 3,818 participants with non-zero CAC scores from the Multiethnic Study of Atherosclerosis and classified them as DM, MetS (without DM) or neither DM/MetS. Risk factor-adjusted CAC density was calculated and examined in relation to incident CHD and CVD events over a median follow-up of 15 years among these three disease groups.ResultsAdjusted CAC density was 2.54, 2.61 and 2.69 among those with DM, MetS or neither DM/MetS. Hazard ratios (HRs) for CHD per 1 SD increase of CAC density was 0.91 (95% CI: 0.72-1.16), 0.70 (95% CI: 0.56-0.87) and 0.79 (95% CI: 0.66-0.95) for those with DM, MetS or neither DM/MetS groups and were 0.77 (95% CI: 0.64-0.94), 0.83 (95% CI: 0.70-0.99) and 0.82 (95% CI: 0.71-0.95) for CVD, respectively. Adjustment for CAC density increased the HRs of CAC volume for CHD/CVD events. Compared to prediction models with or without single CAC measures, c-statistics of models with CAC volume and density were the highest ranging 0.67-0.72.ConclusionCAC density is lower among patients with DM or MetS than those with neither DM/MetS and is inversely associated with future CHD/CVD risk among them. Including CAC density in risk assessment among those with MetS may improve prediction of CHD and CVD.

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)

AimIn statin-treated persons with atherosclerotic cardiovascular disease (ASCVD) the further ASCVD risk that diabetes mellitus (DM) adds is not well-quantified. We examined this residual risk for initial and total recurrent ASCVD events.MethodsWe studied 3271 patients with ASCVD on statin therapy in the AIM-HIGH clinical trial cohort. Cox regression and the Prentice, Williams, and Peterson model examined the excess risk of initial and total recurrent ASCVD events associated with DM over a 3- year mean follow-up. Predictors of first and total ASCVD events in those with and without DM were also examined.ResultsOf our cohort with ASCVD on statin therapy 40% also had DM. Those with vs. without DM were older, were less likely to be male or white. They had higher systolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p

Despite statin therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) still suffer from ASCVD events. Predictors of residual ASCVD risk are not well-delineated. We aimed to develop an ASCVD risk prediction model for patients with previous ASCVD on statin use. We utilized statin-treated patients with ASCVD from the AIM-HIGH trial cohort. A 5-year risk score for subsequent ASCVD events with known ASCVD was developed using Cox regression, including potential risk factors with age, sex, and race forced in the model. Internal discrimination and calibration were evaluated. We included 3,271 patients with ASCVD (85.4% male, mean age 63.6 years, 65% on moderate- and 24% on high-intensity statin) with complete risk factor data and mean follow-up of 4.18 years. Overall, the estimated 5-year ASCVD risk was 21.1%: 10.2% of patients had a 5-year risk of >30%, and 38.8% had risk of between 20% and 30%. In the model, male sex, hemoglobin A1c, alcohol use (inversely), family history of cardiovascular disease, homocysteine, history of carotid artery disease, and lipoprotein(a) best predicted residual ASCVD risk. Niacin treatment status did not enter the model. A C-statistic of 0.59 was obtained, with the Greenwood-Nam-D'Agostino test showing excellent calibration. We developed a risk prediction risk model for predicting 5-year residual ASCVD risk in statin-treated patients with known ASCVD that may help in identifying such persons at the highest risk of recurrent events. Validation in larger samples with patients on high-intensity statin is needed.

Short-term clinical outcomes after transcatheter aortic valve replacement (TAVR) are similar in individuals with small or large annuli. The longer term impact of prosthesis-patient mismatch (PPM) and mean gradient (MG) post-TAVR in these patients remains controversial. The aim of this study was to investigate 5-year outcomes in patients with small vs large annuli. Patients from the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 intermediate-risk registry and the PARTNER 3 low-risk randomized controlled trial were grouped according to small (≤430 mm2) or large (>430 mm2) annular size. The primary endpoint was a composite of all-cause death, disabling stroke, or heart failure hospitalization. In addition, the relationships between both PPM and post-TAVR MG and clinical outcomes were analyzed. In total, 1,355 patients were included: 476 with small annuli (376.7 ± 41.9 mm2) and 879 with large annuli (518.3 ± 58.0 mm2). Patients with small annuli were older (age 79.6 ± 7.1 years vs 78.7 ± 7.8 years; P = 0.047), were more often female (75.0% vs 16.2%; P < 0.0001), had higher baseline Society of Thoracic Surgeons scores (4.3% ± 1.93% vs 4.0% ± 1.93%; P < 0.0001), and had higher left ventricular ejection fractions (66.3% ± 15.82% vs 59.7% ± 13.68%; P < 0.0001). Primary endpoint rates were similar at 1 year (7.8% vs 8.0%; P = 0.94) and 5 years (36.3% vs 35.8%; P = 0.83). Bioprosthetic valve failure was infrequent at 5 years in both groups (2.9% vs 2.1%; P = 0.46). Among female patients, outcomes were similar for small vs large annuli (primary endpoint; 33.6% vs 34.2%; P = 0.90). Among patients with small annuli, there was no association between 5-year outcomes and any severity of PPM (P = 0.22) or 30-day MG (P for nonlinearity = 0.96). Five-year clinical outcomes were excellent and comparable between patients with small vs large aortic annuli. Outcomes in patients with small annuli were not affected by 30-day MG or PPM. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: The extent and relation of multisite atherosclerosis to cardiovascular disease (CVD) in metabolic syndrome (MetS) and diabetes (DM) are not well documented. We examined the extent of multisite atherosclerosis and its prognostic value for CVD events in MetS and DM. METHODS: In CVD-free subjects from the Multi-Ethnic Study of Atherosclerosis, multisite atherosclerosis was measured as: (1) the number of arterial beds involved (coronary calcium>0, abdominal aortic calcium>0, carotid intima-media thickness ≥1 mm and ankle brachial index

BackgroundIndividuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD).HypothesisLung-function measures can predict CVD events in older persons with MetS, DM, and neither condition.MethodsWe followed 4114 participants age ≥ 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1-second forced expiratory volume (FEV1 ; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years.ResultsDM was present in 537 (13.1%) and MetS in 1277 (31.0%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16% (HR: 0.84, 95% CI: 0.59-1.18), 23% (HR: 0.77, 95% CI: 0.60-0.99), and 30% (HR: 0.70, 95% CI: 0.58-0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV1 , CVD risk was lower by 2% (HR: 0.98, 95% CI: 0.70-1.37), 26% (HR: 0.74, 95% CI: 0.59-0.93), and 31% (HR: 0.69, 95% CI: 0.57-0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C-statistics increased significantly with addition of FEV1 or FVC over risk factors for CVD and CHF among those with neither MetS nor DM.ConclusionsFEV1 and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons.

IMPORTANCE: Although the risk of type 2 diabetes is considered to be equivalent to coronary heart disease (CHD) risk, there is considerable heterogeneity among individuals for CHD and atherosclerotic cardiovascular disease (ASCVD) risk. It is not known whether coronary artery calcium (CAC) assessment at baseline in individuals with established metabolic syndrome (MetS) or diabetes identifies CHD and ASCVD prognostic indicators during a long follow-up period. OBJECTIVE: To compare improvement in long-term prognostication of incident CHD and ASCVD using CAC scores among those with diabetes, MetS, or neither condition. DESIGN, SETTING, AND PARTICIPANTS: This study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of 6814 males and females aged 45 to 84 years without known CVD from 4 race/ethnicity groups (white [38.5%], African American [27.5%], Hispanic [22.1%], and Chinese [11.9%]) recruited from 6 US communities from July 2000 through August 2002. Follow-up for each participant extended to the first occurrence of an incident event, other death, loss to follow-up, or the last follow-up call through December 31, 2013. Data analysis was performed from June 1, 2016, to September 12, 2017. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve and net reclassification improvement were used to compare incremental contributions of CAC score when added to the Framingham risk score, ethnicity/race, and socioeconomic status. MAIN OUTCOMES AND MEASURES: CHD events, including myocardial infarction, resuscitated cardiac arrest, or CHD death. RESULTS: Of 6814 MESA participants, 6751 had complete risk factor and follow-up data and were included in this study (mean [SD] age, 62.2 [10.2] years; 3186 [47.2%] male). A total of 881 (13.0%) had diabetes, 1738 (25.7%) had MetS, and 4132 (61.2%) had neither condition. After 11.1 mean years of follow-up, CHD events occurred in 84 participants with diabetes (135 ASCVD events), 115 with MetS (175 ASCVD events), and 157 with neither (250 ASCVD events). The CAC score was independently associated with incident CHD in multivariable analyses in those with diabetes (HR, 1.30; 95% CI, 1.19-1.43), MetS (HR, 1.30; 95% CI, 1.20-1.41), and neither condition (HR, 1.37; 95% CI, 1.27-1.47). For incident CHD, net reclassification improvement with addition of CAC score was 0.23 (95% CI, 0.10-0.37) in those with diabetes, 0.22 (95% CI, 0.09-0.35) in those with MetS, and 0.25 (95% CI, 0.15-0.35) in those with neither condition. The CAC score was also a prognostic indicator of CHD and ASCVD after controlling for diabetes duration of 10 years or longer at baseline, insulin use, and glycemic control. CONCLUSIONS AND RELEVANCE: In a large multiethnic cohort, the addition of CAC score to global risk assessment was associated with significantly improved risk classification in those with MetS and diabetes, even if diabetes duration was longer than a decade, suggesting a role for the CAC score in risk assessment in such patients.

ImportanceAlthough the risk of type 2 diabetes is considered to be equivalent to coronary heart disease (CHD) risk, there is considerable heterogeneity among individuals for CHD and atherosclerotic cardiovascular disease (ASCVD) risk. It is not known whether coronary artery calcium (CAC) assessment at baseline in individuals with established metabolic syndrome (MetS) or diabetes identifies CHD and ASCVD prognostic indicators during a long follow-up period.ObjectiveTo compare improvement in long-term prognostication of incident CHD and ASCVD using CAC scores among those with diabetes, MetS, or neither condition.Design, setting, and participantsThis study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of 6814 males and females aged 45 to 84 years without known CVD from 4 race/ethnicity groups (white [38.5%], African American [27.5%], Hispanic [22.1%], and Chinese [11.9%]) recruited from 6 US communities from July 2000 through August 2002. Follow-up for each participant extended to the first occurrence of an incident event, other death, loss to follow-up, or the last follow-up call through December 31, 2013. Data analysis was performed from June 1, 2016, to September 12, 2017. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve and net reclassification improvement were used to compare incremental contributions of CAC score when added to the Framingham risk score, ethnicity/race, and socioeconomic status.Main outcomes and measuresCHD events, including myocardial infarction, resuscitated cardiac arrest, or CHD death.ResultsOf 6814 MESA participants, 6751 had complete risk factor and follow-up data and were included in this study (mean [SD] age, 62.2 [10.2] years; 3186 [47.2%] male). A total of 881 (13.0%) had diabetes, 1738 (25.7%) had MetS, and 4132 (61.2%) had neither condition. After 11.1 mean years of follow-up, CHD events occurred in 84 participants with diabetes (135 ASCVD events), 115 with MetS (175 ASCVD events), and 157 with neither (250 ASCVD events). The CAC score was independently associated with incident CHD in multivariable analyses in those with diabetes (HR, 1.30; 95% CI, 1.19-1.43), MetS (HR, 1.30; 95% CI, 1.20-1.41), and neither condition (HR, 1.37; 95% CI, 1.27-1.47). For incident CHD, net reclassification improvement with addition of CAC score was 0.23 (95% CI, 0.10-0.37) in those with diabetes, 0.22 (95% CI, 0.09-0.35) in those with MetS, and 0.25 (95% CI, 0.15-0.35) in those with neither condition. The CAC score was also a prognostic indicator of CHD and ASCVD after controlling for diabetes duration of 10 years or longer at baseline, insulin use, and glycemic control.Conclusions and relevanceIn a large multiethnic cohort, the addition of CAC score to global risk assessment was associated with significantly improved risk classification in those with MetS and diabetes, even if diabetes duration was longer than a decade, suggesting a role for the CAC score in risk assessment in such patients.

BackgroundResidual atherosclerotic cardiovascular disease (ASCVD) risk in statin-treated US adults without known ASCVD is not well described.ObjectiveTo quantitate residual ASCVD risk and its predictors in statin-treated adults.MethodsWe studied 1014 statin-treated adults (53.3% female, mean 66.0 years) free of clinical ASCVD in the Multi-Ethnic Study of Atherosclerosis. We examined ASCVD event rates by National Lipid Association risk groups over 11-year follow-up and the relation of standard risk factors, biomarkers, and subclinical atherosclerosis measures with residual ASCVD event risk.ResultsOverall, 5.3% of participants were at low, 12.2% at moderate, 60.3% at high, and 22.2% at very high baseline risk. Despite statin therapy, age- and race-standardized ASCVD rates per 1000 person-years for men and women were both 4.9 for low/moderate risk, 19.1 and 14.2 for high risk, and 35.6 and 26.7 for very high risk, respectively. Specific independent predictors of residual risk included current smoking, family history, diabetes, high-sensitivity C-reactive protein, low-density lipoprotein particle number, carotid intimal medial thickness, and especially coronary artery calcium score. Those on moderate- or high-intensity statins at baseline (compared with low intensity) had 39% lower risks and those who increased statin intensity 62% lower ASCVD event risks (P

BackgroundThe value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain.HypothesisIn older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs.MethodsWe included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning

A stronger association for low-density lipoprotein particle (LDL-P) and high-density lipoprotein particle (HDL-P) versus cholesterol concentrations (LDL-C and HDL-C) in predicting coronary heart disease (CHD) has been noted. We evaluate the role of these factors and extent of particle-cholesterol discordance in those with diabetes mellitus (DM) and metabolic syndrome (MetS) for event prediction. In the Multi-Ethnic Study of Atherosclerosis, we examined discordance of LDL and HDL (defined as a subject's difference between baseline particle and cholesterol percentiles), LDL-C, LDL-P, HDL-C, and HDL-P in relation to incident CHD and cardiovascular disease (CVD) events in subjects with DM, MetS (without DM), or neither condition using Cox regression. Of the 6,417 subjects with 10-year follow-up, those with MetS (n = 1,596) and DM (n = 838) had significantly greater LDL and HDL discordance compared with those without these conditions. In discordance models, only LDL discordance (per SD) within the MetS group was positively associated with CHD events (adjusted hazard ratio [HR] = 1.22, 95% confidence interval [CI] 1.01 to 1.48, p

ObjectiveControlling cardiovascular disease (CVD) risk factors in diabetes mellitus (DM) reduces the number of CVD events, but the effects of multifactorial risk factor control are not well quantified. We examined whether being at targets for blood pressure (BP), LDL cholesterol (LDL-C), and glycated hemoglobin (HbA1c) together are associated with lower risks for CVD events in U.S. adults with DM.Research design and methodsWe studied 2,018 adults, 28-86 years of age with DM but without known CVD, from the Atherosclerosis Risk in Communities (ARIC) study, Multi-Ethnic Study of Atherosclerosis (MESA), and Jackson Heart Study (JHS). Cox regression examined coronary heart disease (CHD) and CVD events over a mean 11-year follow-up in those individuals at BP, LDL-C, and HbA1c target levels, and by the number of controlled risk factors.ResultsOf 2,018 DM subjects (43% male, 55% African American), 41.8%, 32.1%, and 41.9% were at target levels for BP, LDL-C, and HbA1c, respectively; 41.1%, 26.5%, and 7.2% were at target levels for any one, two, or all three factors, respectively. Being at BP, LDL-C, or HbA1c target levels related to 17%, 33%, and 37% lower CVD risks and 17%, 41%, and 36% lower CHD risks, respectively (P < 0.05 to P < 0.0001, except for BP in CHD risk); those subjects with one, two, or all three risk factors at target levels (vs. none) had incrementally lower adjusted risks of CVD events of 36%, 52%, and 62%, respectively, and incrementally lower adjusted risks of CHD events of 41%, 56%, and 60%, respectively (P < 0.001 to P < 0.0001). Propensity score adjustment showed similar findings.ConclusionsOptimal levels of BP, LDL-C, and HbA1c occurring together in individuals with DM are uncommon, but are associated with substantially lower risk of CHD and CVD.

Objective: We examined diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors.Research Design and Methods: We pooled 4 US cohorts (ARIC, JHS, MESA, FHS-Offspring) and classified subjects by baseline DM/CVD. CVD risks between DM+/CVD- vs. DM-/CVD+ were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD- vs. DM-/CVD+.Results: The pooled cohort included 27,730 subjects (mean age of 58.5 years, 44.6% male). CVD rates per 1000 person-years were 16.5, 33.4, 43.2 and 71.4 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. Compared with those with DM-/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use while those with less severe diabetes had lower risks. Hazard ratios (95%CI) for DM+/CVD- vs. DM-/CVD+ were 0.96(0.86-1.07), 0.97(0.88-1.07), 0.96(0.82-1.13), 1.18(0.98-1.41), 0.93(0.85-1.02) and 1.00(0.89-1.13) among women, white race, age <55 years, triglycerides ≥2.26 mmol/L, hs-CRP ≥ 2 mg/L and eGFR<60 mL/min/1.73m2, respectively. In DM+/CVD- group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk.Conclusion: Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function. [ABSTRACT FROM AUTHOR]