Value of addition of coronary artery calcium to risk scores in the prediction of major cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). METHODS: The study examined a population-based cohort of type 2 diabetics (n = 735) aged 55-74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years. RESULTS: Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06-7.86), 6.53 (2.47-17.29) and 8.3 (3.28-21) for CACS of 1-100, 101-300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555-0.676) versus PCE + CACS 0.696 (0.642-0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. CONCLUSIONS: CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.

Relation between Baseline Coronary Atherosclerotic Status, Cardiovascular Events, and Malignancies in Type 2 Diabetics: A Long-Term Prospective Cohort Study.

INTRODUCTION: Coronary artery disease and malignancy occur more frequently in patients with type 2 diabetes. They may share inflammation as a possible common pathogenetic mechanism, but it is unclear whether a clinical correlation exists between them. METHODS: This prospective cohort study followed 735 asymptomatic diabetics, aged 63.4 ± 5.3 years (mean ± standard deviation) for 12.2 ± 0.6 years after baseline coronary artery calcium scoring and cardiac computed tomography angiography. We examined extent and nature of coronary atherosclerosis and incidence of clinical cardiovascular (CV) events (death or myocardial infarction) and sought a relation to incidence of malignancy and malignancy mortality. RESULTS: Total mortality was 16.5% (121/735 patients): malignancy was cause of death in 48/121 (39.7%) of these and CV events in 44/121 (36.3%). There was no relation between extent of coronary atherosclerosis and incident malignancy (plaque volume 127 [21, 427] mm3 (median [interquartile range]) for incident malignancy versus 153 [24, 427] mm3 no malignancy, p = 0.71) or death from malignancy (plaque volume 176 [26, 646] versus 144 [22, 411] mm3, p = 0.32). There was also no relation between presence of high-risk plaque and incident malignancy (high-risk plaque in 27.1% with malignancy vs. 21.6% without, p = 0.18) or fatal malignancy (p = 0.16). Incident and fatal malignancy were not related to clinical CV events. Independent predictors of incident and fatal malignancy were age, smoking at baseline, and elevated C-reactive protein. CONCLUSION: This study found no relation between extent of coronary atherosclerosis or incidence of CV events and malignancy. Malignancy surpassed CV disease as the commonest long-term cause of mortality in middle-aged and older diabetics.

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data.

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780.

Plaque Morphology as Predictor of Late Plaque Events in Patients With Asymptomatic Type 2 Diabetes: A Long-Term Observational Study.

OBJECTIVES: The authors used coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients. BACKGROUND: In patients with coronary artery disease, CTA plaque characteristics may predict mid-term patient events. METHODS: Asymptomatic patients with diabetes 55 to 74 years of age with no history of coronary artery disease (N = 630) underwent baseline 64-slice CTA and detailed plaque level analysis. All subsequent clinical events were recorded and adjudicated. In patients who developed ACS, culprit plaque was identified at invasive angiography and its precursor located on the baseline CTA. Plaque characteristics predicting an ACS-associated culprit plaque event were analyzed by time to event accounting for inpatient clustering of plaques and competing events. RESULTS: Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content <50 Hounsfield units (HR: 14.2; 95% CI: 1.9 to 108; p = 0.010), and mild plaque calcification (HR vs. all other plaques 3.3 [95% CI: 1.5 to 7.3]; p = 0.004) predicted plaque events univariately and after adjustment by clinical risk score. A culprit plaque event occurred in 13 of 376 (3.5%) high-risk plaques (HRP) (plaques with ≥2 risk predictors) versus 11 of 1,866 (0.6%) in non-HRPs (p < 0.0001), at 12 of 343 (3.5%) stenotic sites (≥50%) versus 12 of 1,899 (0.6%) nonstenotic sites (p < 0.0001) and in 7 of 131 (5.3%) HRP with stenosis (p < 0.0001 vs. all others). In 130 (20.6%) subjects, no coronary plaque was present on baseline CTA. CONCLUSIONS: In asymptomatic patients with type 2 diabetes, CTA plaque volume, percent low-density plaque content, and mild calcification predicted late plaque events. The additional presence of luminal stenosis increased the probability of an acute event.

Characterization of Coronary Artery Disease in Young Adults and Assessment of Long-term Outcomes.

BACKGROUND: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited. OBJECTIVES: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography. METHODS: A retrospective analysis (2000-2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted. RESULTS: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15-5.99) and revascularization (HR 4.30, 95%CI 2.01-9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl. CONCLUSIONS: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Correction to: Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Impact of diabetes and early revascularization on the need for late and repeat procedures.

BACKGROUND: Coronary artery disease often progresses more rapidly in diabetics, but the integrated impact of diabetes and early revascularization status on late or repeat revascularization in the contemporary era is less clear. METHODS: Coronary angiography was performed in 12,420 patients between the years 2000-2015 and early revascularization status [none, percutaneous coronary intervention (PCI) or bypass surgery (CABG)] was determined. Subsequent revascularization procedures were recorded over a median follow-up of 67 months and its relation to diabetic and baseline revascularization status was studied. RESULTS: Early revascularization status was none in 5391, PCI in 5682 and CABG in 1347 patients. Late revascularization rates were 10, 26 and 11.1% respectively. Diabetes was present in 37%; a stepwise relationship of diabetic status with late revascularization was observed: no diabetes (reference) 14.4%, non-insulin treated diabetes 21% (adjusted HR 1.35, 95% CI 1.23-1.49, p < 0.001) and insulin-treated diabetes 32.8% (adjusted HR 2.20, 95% CI 1.91-2.54, p < 0.001), which was similar in magnitude for each early revascularization state (none, PCI or CABG). Further revascularizations (≥ 2) were also significantly more common in diabetics, in particular if insulin-treated. Glycosylated hemoglobin level was moderately associated with late revascularization in diabetics after early PCI but not following diagnostic catheterization or CABG. CONCLUSIONS: Diabetic status graded by treatment, and in particular insulin therapy, is a strong predictor for late or repeat revascularization irrespective of early revascularization status. The high rate of repeat revascularization in diabetics following PCI remains a challenging issue.

Influence of Body Mass Index on Long-Term Survival After Cardiac Catheterization.

We examined 18,654 patients who underwent cardiac catheterization in a single center to clarify the association between catheterization indication, body mass index (BMI), and long-term survival over a mean follow-up of 81 months. Patients were grouped by indication for catheterization: (a) acute coronary syndromes (ACS), 7,426 patients; (b) coronary artery disease (CAD) evaluation in stable clinical presentation, 6,911 patients; and (c) primarily non-CAD cardiac evaluations, 4,317 patients. Compared with normal weight, overweight and obesity (but not morbid obesity) was associated with lower risk of long-term mortality. Underweight patients had the greatest risk of mortality. After multivariate adjustment, survival benefit of the overweight and obese was retained in the ACS group [hazard ratio 0.86, 95% confidence interval (0.77-0.96), p = 0.006 and 0.79, (0.68-0.91), p = 0.001, respectively] and in overweight patients in the stable presentation CAD group [0.83, (0.72-0.94), p = 0.005], whereas there was no survival benefit in any of the BMI categories in those catheterized primarily for non-CAD indications. Further analysis of matched cohorts showed similar patterns of survival benefit of the overweight/obese. In conclusion, among patients who underwent cardiac catheterization, an inverse association between BMI and long-term mortality was observed, with the lowest risk noted in the overweight and obese population; the obesity paradox was principally demonstrated in patients with ACS, and was eliminated after covariate adjustment in those catheterized primarily for non-CAD indications.

An Intervention to Reduce the Time Interval Between Hospital Entry and Emergency Coronary Angiography in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. OBJECTIVES: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. METHODS: In March 2013 the authors launched a seven-component intervention program:  Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory Education program for the emergency department staff Dissemination of information regarding the urgency of the PPCI decision Activation of the catheterization team by a single phone call Reimbursement for transportation costs to on-call staff who use their own cars Improvement in the quality of medical records Investigation of failed cases and feedback. RESULTS: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. CONCLUSIONS: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival.

Cardiac Computed Tomography Angiographic Findings as Predictors of Late Heart Failure in an Asymptomatic Diabetic Cohort: An 8-Year Prospective Follow-Up Study.

OBJECTIVES: Predictive models for heart failure (HF) in heterogeneous populations have had limited success. We examined cardiac computed tomography angiography (CTA) predictors of HF or cardiovascular death (HF-CVD) in a prospective study of asymptomatic diabetics undergoing baseline assessment by CTA. METHODS: The subjects (n = 735, aged 55-74 years, 51.2% women) had no clinical history of cardiovascular disease at study entry. Coronary artery calcium (CAC) score, CTA-defined coronary atherosclerosis, cardiac chamber volumes, and clinical data were collected and late outcome events recorded over 8.4 ± 0.6 years (range 7.3-9.3). RESULTS: HF-CVD occurred in 41 (5.6%) subjects, with HF occurring mostly (19/23, 82.6%) in subjects without preceding myocardial infarction. Baseline univariate clinical outcome predictors of HF-CVD included older age (p = 0.027), the duration of diabetes (p = 0.004), HbA1c (p < 0.0001), microvascular disease (retinopathy, microalbuminuria) (p < 0.0001), and systolic blood pressure (p = 0.035). Baseline univariate CTA predictors included CAC score (p = 0.004), coronary stenosis (p = 0.047), and a CTA-defined left/right atrial (LA/RA) volume ratio >1 (p < 0.0001). Independent predictors were an LA/RA volume ratio >1, microvascular disease, and systolic blood pressure (model C-statistic 0.792, 95% CI 0.758-0.824). Measures of the extent of coronary artery disease (CAD) were not independent predictors of HF-CVD. CONCLUSIONS: In a low- to moderate-risk asymptomatic diabetic population, CTA LA enlargement (LA/RA volume ratio) but not the extent of CAD had independent prognostic value for HF-CVD in addition to the clinical variables.

Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). CONCLUSIONS: Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

Impact of Diabetes Mellitus on Long-Term Mortality in Patients Presenting for Coronary Angiography.

To understand the current impact of diabetes mellitus (DM) on long-term outcomes among patients referred for coronary angiography, we studied 14,337 consecutive patients (5,279 diabetic patients [37%]) referred to coronary angiography for assessment or treatment of coronary artery disease. We investigated long-term all-cause mortality and its interaction with hypoglycemic therapy and presenting coronary status. At baseline, patients with DM had more hypertension, hyperlipidemia, and renal failure; more were women, overweight, and more had previous coronary interventions. Mortality was higher in those with DM and was related to treatment status: multivariate adjusted hazard ratio during a median follow-up period of 78 months was 1.41 (95% CI 1.11 to 1.80, p = 0.006) for diet only-treated DM, 1.63 (95% CI 1.51 to 1.77, p <0.001) for DM treated with oral hypoglycemics, and 2.50 (95% CI 2.20 to 2.85, p <0.001) for DM requiring insulin therapy. The earlier findings were similar in magnitude in patients presenting with acute or stable coronary syndromes. In addition, long-term mortality of medically treated DM presenting with a stable coronary syndrome was even higher than that of nondiabetic patients presenting with an acute coronary syndrome (hazard ratio 1.21, 95% CI 1.08 to 1.35, p = 0.001). In conclusion, in patients referred for coronary angiography in the current era, DM remained an independent predictor of long-term mortality regardless of the coronary presentation and mortality increased in direct relation to intensity of hypoglycemic therapy at presentation.

Clinical determinants and treatment gaps in familial hypercholesterolemia: Data from a multi-ethnic regional health service.

Background Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community. Methods A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated. Results Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50-74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252-288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p < 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol < 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking. Conclusions The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.

Identification and characterization of severe familial hypercholesterolemia in patients presenting for cardiac catheterization.

BACKGROUND: Patients with severe familial hypercholesterolemia (FH) are often unrecognized despite typical presentation. The introduction of PCSK9 inhibitors opens new therapeutic options and emphasizes the need for identification of severe FH patients. OBJECTIVES: The objective was identification, characterization, and management of severe FH patients by screening of cardiac catheterization (CC) database. METHODS: Retrospective analysis of CC database from 2002 to mid-2015 was performed for low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (n = 2383). Severe FH was diagnosed if any prior LDL-C was ≥280 mg/dL, excluding secondary causes. Peak/current LDL-C levels and lipid-lowering therapies were evaluated. Initial attempt was made to detect relatives with FH according to identifying data and age-dependent LDL-C cutoffs. RESULTS: Severe FH was identified in 54 of initial 2382 patients with CC LDL-C ≥130 mg/dL. Mean age at cardiovascular disease diagnosis was 45 years. Peak LDL-C was 280 to 464 mg/dL (median, 322). Coronary artery bypass graft surgery was performed in 26 patients (48%) and redo coronary artery bypass graft surgery in 5 patients (9%). Risk factors included obesity (33%), hypertension (59%), smoking (33%), and diabetes (24%). LDL-C reduction ≥50% of peak value was achieved in 56%, LDL-C <130 mg/dL in 32%, and LDL-C <100 mg/dL in 17% of patients. High-intensity statin plus ezetimibe was prescribed for 67%, high-intensity statin alone for 24%, and other lipid-lowering therapies for 9% of patients. Treatment intensity was directly associated with attainment of LDL-C goals. Matching probands' surnames and place of residency with district health maintenance organization database has identified 161 additional individuals with possible FH; 58% were not treated with lipid-lowering drugs. CONCLUSIONS: A simple algorithm for identification of patients with severe FH was implemented based on large catheterization and health maintenance organization databases and revealed patients with severe FH and coronary disease at a young age, with low attainment of cholesterol treatment goals. Screening existing cardiovascular databases of populations at risk will promote identification and management of severe FH patients and their affected family members.

Coronary Computed Tomography (CT) Angiography as a Predictor of Cardiac and Noncardiac Vascular Events in Asymptomatic Type 2 Diabetics: A 7-Year Population-Based Cohort Study.

BACKGROUND: Type 2 diabetics are at increased risk for vascular events, but the value of further risk stratification for coronary heart disease (CHD) in asymptomatic subjects is unclear. We examined the added value of coronary computed tomography angiography over clinical risk scores (United Kingdom Prospective Diabetes Study), and coronary artery calcium in a population-based cohort of asymptomatic type 2 diabetics. METHODS AND RESULTS: Subjects (n=630) underwent baseline clinical assessment and computed tomography angiography (64-slice scanner). Plaque site, volume, calcific content, and arterial remodeling were recorded using dedicated software. Coronary, macrovascular, and microvascular-related events were assessed over 6.6±0.6 (mean±SD) (range 5.4-7.5) years and all CHD events were adjudicated. Discrimination of CHD events (cardiovascular death, myocardial infarction, unstable angina, or new-onset angina requiring intervention) (n=41) was improved by addition of total plaque burden to the clinical risk and coronary artery calcium scores combined (C=0.789 versus 0.763, P=0.034) and further improved by addition of an angiographic score (C=0.824, P=0.021). Independent predictors of a CHD event were United Kingdom Prospective Diabetes Study risk score (hazard ratio 1.3 per 10% 10-year risk, P=0.003) and the angiographic score (hazard ratio 3.2 per quartile, P<0.0001). Classification was improved over that by United Kingdom Prospective Diabetes Study and coronary artery calcium scores alone (overall net reclassification improvement 0.24). In subjects with coronary plaque (N=500), mild plaque calcification independently predicted a CHD event (hazard ratio 3.0, P=0.02). Computed tomography angiography predicted combined macrovascular but not microvascular-related events. CONCLUSIONS: Computed tomography angiography provides additional prognostic information in asymptomatic type 2 diabetics not obtainable from clinical risk assessment and coronary artery calcium alone.

Long-Term Radial Artery Patency Following Transradial Coronary Catheterization via a 7-Fr Sheath.

BACKGROUND: Radial artery occlusion (RAO) may occur following transradial catheterization, precluding future use of the vessel for vascular access or as a coronary bypass graft. Recanalization of RAO may occur; however, long-term radial artery patency when revascularization is more likely to be required has not been investigated. Transradial catheterization is usually performed via 5-Fr or 6-Fr catheters. Insertion of 7-Fr sheaths into the radial artery enables complex coronary interventions but may increase the risk of RAO. OBJECTIVE: To assess the long-term radial artery patency following transradial catheterization via 7-Fr sheaths. METHODS: Antegrade radial artery blood flow was assessed by duplex ultrasound in 43 patients who had undergone transradial catheterization via a 7-Fr sheath. RESULTS: All patients had received intravenous unfractionated heparin with a mean activated clotting time (ACT) of 247 ± 56 seconds. Twenty-four patients (56%) had received a glycoprotein IIbIIIa inhibitor and no vascular site complications had occurred. Mean time interval from catheterization to duplex ultrasound was 507 ± 317 days. Asymptomatic RAO was documented in 8 subjects (19%). Reduced body weight was the only significant univariate predictor of RAO (78 ± 11 vs. 89 ± 13 kg, P = 0.031). In a bivariate model using receiver operator characteristic (ROC) curves, the combination of lower weight and shorter ACT offered best prediction of RAO (area under the ROC curve 0.813). CONCLUSIONS: Asymptomatic RAO was found at late follow-up in approximately 1 of 5 patients undergoing transradial catheterization via a 7-Fr sheath and was associated with lower body weight and shorter ACT.

Resting heart rate and measures of effort-related cardiac autonomic dysfunction predict cardiovascular events in asymptomatic type 2 diabetes.

BACKGROUND: Autonomic control of the cardiovascular system may be impaired in type 2 diabetes and is associated with increased morbidity and mortality. Parameters obtained during stress testing may reflect early stages of cardiac autonomic dysfunction and provide prognostic information in asymptomatic type 2 diabetes. METHODS: We performed maximal exercise treadmill testing in 594 patients with type 2 diabetes without known coronary heart disease. The prognostic significance of physiological parameters associated with autonomic dysfunction was assessed, including chronotropic incompetence (<80% heart rate reserve), abnormal heart rate recovery at 1 minute <18 beats/minute, and resting tachycardia >100 beats/minute. Cox proportional hazards analysis was used to determine the association of exercise parameters with a composite outcome of all-cause mortality, myocardial infarction or stroke. RESULTS: Resting heart rate >100 beats/minute was observed in 18% of patients, chronotropic incompetence in 30% and heart rate recovery at 1 minute <18 beats/minute in 35%. Over 79 ± 16 months, there were 72 (12%) events. Each parameter was significantly associated with event risk in an adjusted multivariate analysis: chronotropic incompetence (hazard ratio 1.89, 95% confidence interval 1.18-3.01; P = 0.008), resting heart rate ≥100 beats/minute (hazard ratio 1.97, 95% confidence interval 1.19-3.26; P = 0.008) and heart rate recovery at 1 minute <18 beats (hazard ratio 1.77, 95% confidence interval 1.12-2.81; P = 0.015). A progressive relationship between the number of abnormal parameters and event risk was observed (log rank P < 0.001). CONCLUSIONS: Chronotropic incompetence, resting tachycardia and reduced heart rate recovery are independently and additively associated with long-term mortality, myocardial infarction or stroke in type 2 diabetes without known coronary heart disease.

Automated Computer-Assisted Diagnosis of Obstructive Coronary Artery Disease in Emergency Department Patients Undergoing 256-Slice Coronary Computed Tomography Angiography for Acute Chest Pain.

A 256-slice coronary computed tomography angiography (CCTA) is an accurate method for detection and exclusion of obstructive coronary artery disease (OBS-CAD). However, accurate image interpretation requires expertise and may not be available at all hours. The purpose of this study was to evaluate the usefulness of a fully automated computer-assisted diagnosis (COMP-DIAG) tool for exclusion of OBS-CAD in patients in the emergency department (ED) presenting with chest pain. Three hundred sixty-nine patients in ED without known coronary disease underwent 256-slice CCTA as part of the assessment of chest pain of uncertain origin. COMP-DIAG (CorAnalyzer II) automatically reported presence or exclusion of OBS-CAD (>50% stenosis, ≥1 vessel). Performance characteristics of COMP-DIAG for exclusion and detection of OBS-CAD were determined using expert reading as the reference standard. Seventeen (5%) studies were unassessable by COMP-DIAG software, and 352 patients (1,056 vessels) were therefore available for analysis. COMP-DIAG identified 33% of assessable studies as having OBS-CAD, but the prevalence of OBS-CAD on CCTA was only 18% (66 of 352 patients) by standard expert reading. However, COMP-DIAG correctly identified 61 of the 66 patients (93%) with OBS-CAD with 21 vessels (2%) with OBS-CAD misclassified as negative. In conclusion, compared to expert reading, automated computer-assisted diagnosis using the CorAnalyzer showed high sensitivity but only moderate specificity for detection of obstructive coronary disease in patients in ED who underwent 256-slice CCTA. The high negative predictive value of this computer-assisted algorithm may be useful in the ED setting.