Extent of subclinical atherosclerosis on coronary computed tomography and impact of statins in patients with diabetes without known coronary artery disease: Results from CONFIRM registry

BackgroundAbsence of subclinical atherosclerosis is considered safe to defer statin therapy in general population. However, impact of statins on atherosclerotic cardiovascular disease in patients with diabetes stratified by coronary artery calcium (CAC) scores and extent of non-obstructive CAD on coronary computed tomography angiography (CCTA) has not been evaluated.MethodsCONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multi-center Registry) study enrolled consecutive adults 18 years of age between 2005 and 2009 who underwent ³64-detector row CCTA for suspected CAD. The long-term registry includes data on 12,086 subjects who underwent CCTA at 17 centers in 9 countries. In this sub-study of CONFIRM registry, patients with diabetes mellitus (DM) and without diabetes mellitus with normal CCTA or non-obstructive plaque (<50 % diameter stenosis) for whom data on baseline statin use was available were included. CAC score was calculated using Agatston score. The magnitude of non-obstructive coronary artery disease on CCTA was quantified using segment involvement score (SIS). Primary outcome was major cardiovascular events (MACE) which included all-cause mortality, myocardial infarction, and target vessel re-vascularization.ResultsA total of 7247 patients (Mean age 56.8 years) with a median follow up of 5 years were included. For DM patients, baseline statin therapy significantly reduced MACE for patients with CAC ≥100 (HR: 0.24; 95 % CI 0.07–0.87; p = 0.03) and SIS≥3 (HR: 0.23; 95 % CI 0.06–0.83; p = 0.024) compared to those not on statin therapy. Among Diabetics with lower CAC (<100) and SIS (≤3) scores, MACE was similar in statin and non-statin groups. In contrast, among non-DM patients, MACE was similar in statin and no statin groups irrespective of baseline CAC (1–99 or ≥100) and SIS.ConclusionIn this large multicenter cohort of patients, the presence and extent of subclinical atherosclerosis as assessed by CAC and SIS identified patients most likely to derive benefit from statin therapy.     

Atherosclerotic Cardiovascular Disease or Heart Failure: First Cardiovascular Event in Adults With Prediabetes and Diabetes

BackgroundIndividuals with prediabetes and diabetes are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Whether ASCVD or HF is more likely to occur first in these populations within different race-sex groups is unknown.ObjectiveTo determine the competing risk for the first cardiovascular event by subtype in Black and white men and women with prediabetes and diabetes.MethodsIndividual-level data from adults without ASCVD or HF were pooled from 6 population-based cohorts. We estimated the competing cumulative incidences of ASCVD, HF and noncardiovascular death as the first event in middle-aged (40–59 years) and older (60–79 years) adults, stratified by race and sex, with normal fasting plasma glucose (FPG < 100 mg/dL), prediabetes (FPG 100–125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) at baseline. Within each race-sex group, we estimated risk the adjusted hazard ratio of ASCVD, HF and noncardiovascular death in adults with prediabetes and diabetes relative to adults with normoglycemia after adjusting for cardiovascular risk factors.ResultsIn 40,117 participants with 638,910 person-years of follow-up, 5781 cases of incident ASCVD and 3179 cases of incident HF occurred. In middle-aged adults with diabetes, competing cumulative incidence of ASCVD as a first event was higher than HF in white men (35.4% vs 11.6%), Black men (31.6% vs 15.1%) and white women (24.3% vs 17.2%) but not in Black women (26.4% vs 28.4%). Within each group, the adjusted hazard ratio of ASCVD and HF was significantly higher in adults with diabetes than in adults with normal FPG levels. Findings were largely similar in middle-aged adults with prediabetes and older adults with prediabetes or diabetes.ConclusionsBlack women with diabetes are more likely to develop HF as their first CVD event, whereas individuals with diabetes from other race-sex groups are more likely to present first with ASCVD. These results can inform the tailoring of primary prevention therapies for either HF- or ASCVD-specific pathways based on individual-level risk.     

Lipid management beyond the guidelines

The 2018 AHA/ACC cholesterol guideline builds on the 2013 ACC/AHA cholesterol guideline statin recommendations to provide more detailed recommendations for the use of nonstatin therapy risk stratification for primary prevention statin use. New information has become available after the development of the 2018 AHA/ACC cholesterol guideline that can further inform clinical practice. Proprotein convertase subtilisin kexin type-9 (PCSK9) monoclonal antibodies are now a reasonable or even good value following over 60% reductions in their acquisition price, and the identification of high risk patient groups most likely to benefit from further low-density lipoprotein cholesterol (LDL-C) lowering. Meta-analyses and clinical trial data now show that patients with LDL-C ≥ 100 mg/dl are more likely to experience progressively greater reductions in the risk of cardiovascular and total mortality and coronary heart disease events for progressively higher LDL-C levels. Icosapent ethyl, a highly concentrated form of modified EPA has been shown to reduce cardiovascular events in high risk patients with moderate hypertriglyceridemia on statin therapy. Comparisons with other statin guidelines revealed that statin initiation for those with ≥7.5% 10-year atherosclerotic cardiovascular disease (ASCVD) risk is the most effective strategy for reducing the most ASCVD events for the proportion of the population treated. Data from younger populations finally became available for coronary artery calcium (CAC) scoring (mean age of 51 years) which confirmed the value of CAC > 0 for identifying individuals at increased ASCVD risk most likely to benefit from statin initiation. This analysis also found that statins could keep CAC = 0 in those with risk factors. Epidemiologic pooling studies now clearly show that LDL-C and non-high-density lipoprotein cholesterol levels in young adulthood confer excess risk for ASCVD later in life. Accumulating data support earlier risk factor intervention trials as the next research priority.     

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study

AimsLow blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.Methods2423 participants were randomized to 4000 IU/day of vitamin D₃ or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE.ResultsMean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (?0.45 %, 95%CI -0.75 to ?0.15).ConclusionsIn people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.Trial registration: D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.     

Impact of unknown diabetes and prediabetes on clinical outcomes in “nondiabetic” Chinese patients after a primary coronary intervention

Background and aimTo explore the prevalence of unknown diabetes (DM) or prediabetes (pre-DM) in “nondiabetic” patients and its association with 2-year clinical outcomes after primary percutaneous coronary intervention (PCI).Methods and results5202 consecutive “nondiabetic” patients who underwent primary PCI at Fuwai Hospital from January to December 2013 were prospectively enrolled. The patients were grouped according to their glycemia status: unknown DM (HbA1c ≥ 47 mmol/L; FPG≥ 7.0 mmol/L), pre-DM (HbA1c 39–47 mmol/L; FPG: 5.6–6.9 mmol/L) and normoglycemia (NG, HbA1c < 39 mmol/L; FPG < 5.6 mmol/L). The main endpoint was 2-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, and target vessel revascularization. A total of 905 patients had unknown DM, and 3407 patients had pre-DM. Unknown DM and pre-DM were associated with aging (p < 0.001); a greater proportion of hypertension (p < 0.001), previous myocardial infarction (p < 0.001), and chronic kidney disease (p = 0.004). During the 2-year follow-up, the rate of MACE was significantly higher in the unknown DM and pre-DM groups than in the NG group (8.1% vs. 5.8% vs. 4.1%, respectively, p = 0.001). Multivariate analyses demonstrated that unknown DM was associated with a 1.9-fold higher event risk compared to NG (95% CI: 1.2–2.8).ConclusionsThe prevalence of abnormal glucose metabolism was high in “nondiabetic” Chinese PCI patients. Patients with unknown DM and pre-DM had higher event risks than those with NG. In “nondiabetes” patients requiring PCI, routine assessment of HbA1c and FPG appears to be of value to identify patients with an increased event risk.     

Cardiovascular Disease Risk and Statin Use Among Adults with Metabolic Dysfunction Associated Fatty Liver Disease

BackgroundA leading cause of mortality in fatty liver disease is cardiovascular disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is new terminology that classifies fatty liver due to metabolic dysfunction attributable to obesity and associated complications. We evaluated atherosclerotic cardiovascular disease (ASCVD) risk and statin use in adults with MAFLD.MethodsThis was a retrospective study of the 2011-2018 National Health and Nutrition Examination Survey. Adults with MAFLD were identified using established criteria: presence of hepatic steatosis (US Fatty Liver Index>30) plus ≥1 of the following: 1) body mass index >25 kg/m² in non-Asians or >23 kg/m² in Asians, 2) diabetes mellitus, and 3) ≥2 metabolic risk factors. Cardiovascular disease risk was estimated using the validated 10-year ASCVD risk score. Statin use was assessed in intermediate and high 10-year ASCVD risk groups.ResultsPrevalence of MAFLD was 34.8% (95% confidence interval [CI], 33.9%-35.8%), comprising 54.4% males, 27.9% aged 65 years and older, and 38.2% non-Hispanic white. Among adults with MAFLD, 23.3% and 23.0% had intermediate and high 10-year ASCVD risk, respectively. Compared with females, males were more likely to have high 10-year ASCVD risk (28.7% vs 16.1%, adjusted odds ratio 5.24, 95% CI, 3.87-7.10, P < .01). In intermediate and high ASCVD risk groups, overall statin use was 48.3% (95% CI, 46.1-51.3).ConclusionsOver 46% of adults with MAFLD had intermediate or high 10-year ASCVD risk. Statin use was underutilized at 48.3% in those meeting statin criteria. These findings are alarming given the high cardiovascular disease risk and low statin use in this cohort.     

Dental Clinics as Potent Sources for Screening Undiagnosed Diabetes and Prediabetes

IntroductionThis pilot study investigated the efficacy of dental clinics as potent sources for screening diabetes and prediabetes in undiagnosed individuals.MethodsData were randomly collected from 385 patients (aged 40 years and older) visiting dental clinics. Patients already having a diagnosis of diabetes and/or prediabetes were excluded. Demographic data, body mass index and family and dental histories were recorded. Signs and symptoms of diabetes were investigated. Random blood glucose levels (RBGLs) were recorded. Individuals with RBGL ≥110 mg/dL underwent the oral glucose tolerance test and the glycosylated hemoglobin test (HbA1c).ResultsOf the 385 patients, 60% (232) had RBGL <110 mg/dL, whereas 40% (153) had RBGL ≥110 mg/dL. Prevalence of confirmed diabetes and prediabetes among the study participants was 16.4% and 15.8%, respectively. Body mass index was significantly higher among patients with diabetes and prediabetes as compared with healthy controls. HbA1c level was statistically significantly higher among patients with diabetes than among patients with prediabetes. Symptoms of polyuria and polydipsia were significantly higher among patients with diabetes than in those without diabetes.ConclusionsA high percentage of undiagnosed type 2 diabetes and prediabetes among patients visiting dental clinics was found compared with that reported in the medical literature. Further studies with a lager sample size are needed to confirm these results.     

CAC for Risk Stratification Among Individuals With Hypertriglyceridemia Free of Clinical Atherosclerotic Cardiovascular Disease

ObjectivesIn this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among individuals with hypertriglyceridemia in primary prevention. The eligibility criteria for icosapent ethyl (IPE) were used as case example.BackgroundRecent trials of atherosclerotic cardiovascular disease (ASCVD) risk-reduction therapies for individuals with hypertriglyceridemia without clinical ASCVD restricted enrollment to participants with diabetes or various other risk factors. These criteria were mirrored in the Food and Drug Administration product label for IPE.MethodsWe pooled 2,345 participants with triglycerides 150 to <500 mg/dL (or >178-<500 mg/dL if not on a statin) and without clinical ASCVD from MESA, CARDIA, the Dallas Heart Study, and the Heinz Nixdorf Recall study. We evaluated the incidence of ASCVD events overall, by IPE eligibility (as defined in the product label), and further stratified by CAC scores (0, >0-100, >100). The number needed to treat for 5 years (NNT₅) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT₅ was also estimated among noneligible participants.ResultsThere was marked heterogeneity in CAC burden overall (45% CAC 0; 24% CAC >100) and across IPE eligibility strata. Overall, 17% of participants were eligible for IPE and 11.9% had ASCVD events within 5 years. Among participants eligible for IPE, 38% had CAC >100, and their event rates were markedly higher (15.9% vs 7.2%) and the NNT₅ 2.2-fold lower (29 vs 64) than those of the 25% eligible participants with CAC 0. Among the 83% participants not eligible for IPE, 20% had CAC >100, and their 5-year incidence of ASCVD (13.9%) was higher than the overall incidence among IPE-eligible participants.ConclusionsCAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia without clinical ASCVD. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC >100 to enroll a high-risk study sample, with implications for a larger target population.     

Machine Learning Adds to Clinical and CAC Assessments in Predicting 10-Year CHD and CVD Deaths

ObjectivesThe aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.BackgroundThe CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.MethodsThe study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).ResultsThe AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001).ConclusionsThe comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.     

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

Background and aimsWe aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia.Methods and resultsNinety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39–46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT.ConclusionsSubjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases.     

Sex-influenced association between free triiodothyronine levels and poor glycemic control in euthyroid patients with type 2 diabetes mellitus

ObjectiveThe study investigated the association between free triiodothyronine (FT3) and poor glycemic control with different definitions in euthyroid patients with type 2 diabetes mellitus (T2DM).MethodsThis was a cross-sectional study which included 2172 patients from National Metabolic Management Center in Ruijin Hospital. The association between thyroid function and glycated hemoglobin A1c (HbA1c) was determined by multiple liner regression models. The association between FT3 and poor glycemic control was further determined by binary logistic regression models. Two definitions of poor glycemic control (HbA1c ≥ 7% and HbA1c ≥ 8%) were applied when we analyzed the association.ResultsPrevalence of HbA1c ≥ 7% and HbA1c ≥ 8% were 63.8% and 39.3%, respectively. After adjusting for confounding factors, FT3, rather than free tetraiodothyronine (FT4) or thyroid stimulating hormone (TSH), was independently associated with HbA1c (β = −0.104, P = 0.002). Further analysis after gender stratification showed that the association was only found in males (β = −0.164, P < 0.001). We further analyzed the association between FT3 quartiles and poor glycemic control. FT3 quartiles were not significantly associated with the risk of HbA1c ≥ 7% before and after adjusting for confounding factors in both genders. FT3 quartiles were negatively associated with the risk of HbA1c ≥ 8% only in males, independent of traditional risk factors for poor glycemic control (P for trend = 0.030).ConclusionsFT3 in the reference range was significantly associated with reduced risk of HbA1c ≥ 8% in males, independent of traditional risk factors for poor glycemic control.     

Sex disparities in cardiovascular disease outcomes among geriatric patients with prediabetes

AimsTo analyze the sex-based differences in the prevalence of cardiovascular disease risk factors and outcomes in older patients with prediabetes using demographically matched national cohorts of hospitalized patients aged ≥65 years.MethodsWe queried the 2007–2014 National Inpatient Database to identify older patients (>65 years) admitted with prediabetes using ICD-9 Clinical Modification codes. The older patients were then subcategorized based on sex. Comparative analyses of their baseline characteristics, the prevalence of cardiovascular(CV) disease comorbidities, hospitalization outcomes, and mortality rates were performed on propensity-matched cohorts for demographics.ResultsA total of 1,197,978 older patients with prediabetes (599,223 males; mean age 75years and 598,755 females; mean age 76years) were identified. Higher admission rates were found commonly among older white males (84.1%) and females (81.7%). Prediabetic older males showed a higher frequency of cardiovascular comorbidities compared to females. Prediabetic older males had higher all-cause in-hospital mortality (4.2% vs. 3.6%, p < 0.001), acute myocardial infarction (7.0% vs. 4.7%, p < 0.001), arrhythmia (36.3% vs. 30.5%, p < 0.001), stroke (4.8% vs. 4.6%, p < 0.001), venous thromboembolism (3.3% vs. 3.0%, p < 0.001) and percutaneous coronary intervention (3.1% vs. 1.5%, p < 0.001) compared to females.ConclusionsOur analysis revealed that among older patients hospitalized with prediabetes, males suffered worse in-hospital CV outcomes and survival rates compared to females.     

Abdominal obesity and incident cardio-metabolic disorders in Asian-Indians: A 10-years prospective cohort study

Background and aimsTo estimate the strength of association between abdominal obesity and incident cardio-metabolic diseases.MethodsA subset of Chandigarh Urban Diabetes study cohort (n = 543) was followed after a mean of 10.7 years for development of diabetes, prediabetes, dysglycaemia (either prediabetes or diabetes), hypertension and atherosclerotic cardiovascular disease (ASCVD). Diabetes and prediabetes were defined as per American Diabetes Association consulting group criteria, hypertension as blood pressure of ≥140/90 mmHg and ASCVD after review of medical records. Abdominal obesity was defined as waist circumference of ≥80 cm and ≥90 cm in females and males, respectively.ResultsAs compared to non-obese (n = 209), abdominally obese individuals (n = 334) had a higher risk of diabetes [RR:1.82(1.28–2.57)], prediabetes [RR:1.40(1.05–1.85)], dysglycaemia [ RR:1.38(1.07–1.78)], hypertension [RR: 1.84(1.30–2.59)] and ASCVD [RR:2.12(1.02–4.4)]. The optimal cut-off of waist circumference for detecting incident diabetes, hypertension and ASCVD in females was 88 cm, 85 cm and 91 cm, respectively; while in males it was 90 cm, 87 cm and 94 cm, respectively.ConclusionIn Asian-Indians, abdominal obesity as defined by waist circumference of ≥90 cm and ≥80 cm in males and females, respectively is associated with a twofold higher risk of diabetes, hypertension and ASCVD. In addition, the current-cut-offs of waist circumference to define abdominal obesity need reconsideration to optimally identify individuals at a higher risk of cardio-metabolic diseases. However, a high attrition rate represents a major limitation.     

Effects of aerobic training and resistance training in reducing cardiovascular disease risk for patients with prediabetes: A multi-center randomized controlled trial

AimsAerobic training (AT) and resistance training (RT) can reduce blood glucose and type 2 diabetes risk, and increase muscle mass for prediabetes patients. However, the impact of long-term AT and RT on cardiovascular disease (CVD) risk remains unclear. The purpose of this study was to investigate the impact of AT and RT on CVD risk reduction in prediabetes patients.Materials and methods248 prediabetes patients were enrolled in this multi-center randomized controlled trial (RCT). Patients were randomly divided into 3 groups: RT (n = 82), aerobic training (AT (n = 83)), and control group (n = 83). Participants in RT and AT groups had moderate RT or AT 3 times a week (150 min/week) under supervision in 3 research centers for 24 months. Primary outcome was CVD risk measured by Framingham Risk Score (FRS) and The Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool. Secondary outcomes included in HOMA2-IR, HbA1c, blood pressure and serum lipid profile.ResultsBoth RT and AT groups experienced a significant reduction in HOMA2-IR, HbA1c, LDL-C, TC, SBP, and DBP at the end of 12 and 24 months. Compared to the control group, Both RT and AT groups had significant reduction of the Chinese 10-year ICVD risk (P < 0.05), but FRS CVD risk declined significantly only in the AT group (all P < 0.05). Although FRS CVD risk decreased more in the RT group than in the control group, the difference was not statistically significant. After adjusting for age, gender, statin use, BMI, and WHR, in COX’s proportional hazard model, RT (HR = 0.419, P = 0.037) and AT (HR = 0.310, P = 0.026) were protective factors for CVD risk in prediabetes patients. 24-month RT and AT decreased respectively 58.1% and 69.0% of CVD risk (10-year ICVD risk assessment) in prediabetes patients.ConclusionsThis study demonstrated that 24-month moderate AT reduces the Chinese 10-year ICVD risk and FRS CVD risk in prediabetes patients. RT groups had significant reduction of CVD risk (10-year ICVD risk assessment) in prediabetes patients.Trial registrationClinical trial registration number: NCT 02561377.Date of registration24/09/2015.     

Hemoglobin glycation index is associated with incident chronic kidney disease in subjects with impaired glucose metabolism: A 10-year longitudinal cohort study

AimWe investigated the associations between hemoglobin glycation index (HGI) and incident chronic kidney disease (CKD) in treatment-naïve subjects with prediabetes or diabetes.MethodsWe conducted a prospective cohort study comprising 2187 subjects with prediabetes or diabetes. HGI was calculated as the difference between the measured and predicted values of HbA1c using the linear relationship between HbA1c level and fasting plasma glucose levels. Incident CKD was considered if eGFR decreased to <60 mL/min/1.73 m² and by >25% from the baseline value during follow up. The hazard ratios (HRs) for incident CKD were calculated using Cox proportional hazards regression models.ResultsThe overall prevalence of CKD was 15.3% (n = 335) during the 10-year follow-up period. The prevalence of CKD increased significantly from the low to the high HGI groups. In the multivariate analysis, the highest HGI group showed the highest adjusted HR for incident CKD (HR, 1.57; 95% confidence interval, 1.06–2.34), and this remained significant even after adjusting for the HbA1c level.ConclusionsHigh HGI was associated with an increased risk of incident CKD among treatment-naïve subjects with prediabetes or diabetes, suggesting that HGI may be used to predict CKD in these patients regardless of HbA1c levels.     

Prevalence and risk factors for diabetic retinopathy in prediabetes in Asian Indians

AimTo assess the prevalence of diabetic retinopathy (DR) and associated risk factors in Asian Indians with prediabetes.MethodsIn a cross-sectional study conducted at two tertiary care diabetes centres in Chennai, India, clinical and biochemical assessment and nonmydriatic ultra-wide field fundus photography was performed in individuals with prediabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) based on oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c) between 5.7% and 6.4% in 2019. The retinal photographs were graded by certified ophthalmologists. Systemic risk factors associated with DR in prediabetes were assessed.ResultsThe mean age of the 192 individuals with prediabetes was 48 ± 13 years (55.2% were males). DR was present in 12 (6.3%) individuals of which nine (4.7%) had mild non-proliferative DR (NPDR) and three (1.6%) had moderate NPDR. None had severe sight-threatening DR. The Poisson multiple regression analysis showed that after adjusting for other systemic covariates, HbA1c values ≥ 6% (6–6.4%) was associated with 2 times higher relative risk of DR (Risk ratio 1.95 (95% CI 1.07–3.545, p = 0.028) in comparison to HbA1c < 6%).ConclusionDR was present in about 6% of the Asian Indians with prediabetes. Higher HbA1c values among individuals with prediabetes was associated with twice the relative risk for DR. Robust control of HbA1c should be encouraged even before the diagnosis of diabetes is established.     

The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.     

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AimsThe clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.MethodsWe recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3–6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7–6.4%, 39–46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.ResultsEighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥165 mg/dL and a 30-min C-peptide <5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98–26.16) of developing diabetes than other prediabetic subjects.ConclusionsIn Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.     

Statin Use for Primary Cardiovascular Disease Prevention Is Low in Inflammatory Arthritis

BackgroundPatients with inflammatory arthritis (IA) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet management of dyslipidemia is infrequently prioritized. We applied Canadian dyslipidemia guidelines to determine how many patients with IA would be eligible for primary prevention with statins.MethodsWe conducted a cross-sectional study of patients with IA in a cardio-rheumatology clinic, with no known CVD and without statin therapy at cohort entry. We stratified patients by Framingham Risk Score (FRS) and summarized the proportion meeting guideline statin-indicated criteria. Multivariable logistic regression analyses determined the association of variables with statin indication after adjustment for age, sex, traditional ASCVD risk factors, and arthritis characteristics.ResultsAmong 302 patients, most had rheumatoid arthritis (59%). Mean age was 58 years, and 71% were female. Overall, 50% of the cohort was eligible for statin therapy. The majority was low FRS risk category (68%), and the most frequent qualifier for statins was elevated apolipoprotein B (ApoB) levels or low-density lipoprotein cholesterol (LDL-c) levels. In the intermediate FRS group, 91% met criteria for statin therapy based on the presence of a coronary artery calcification (CAC) score > 0 or an elevated high-sensitivity C-reactive protein. Male sex, hypertension, elevated ApoB, and a CAC score > 0 were the factors most strongly associated with indication for statin therapy.ConclusionsStatin therapy is suboptimal in IA despite a significant number of patients meeting indication based on lipoprotein thresholds or CAC scores. Understanding the barriers and potential facilitators of implementing and interpreting these CVD screening tools in IA is needed.     

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

ObjectivesThe aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy.BackgroundFH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH.MethodsSubjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis.ResultsA total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001).ConclusionsCAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.