Effects of a patient-centered digital health intervention in patients referred to cardiac rehabilitation: the Smart HEART clinical trial.

BACKGROUND: Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures. METHODS: Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention. RESULTS: Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT (mean difference [MD] -29 m; 95% CI, 10 to 49; P < 0.01) and low-density lipoprotein cholesterol (MD -11 mg/dL; 95% CI, -17 to -5; P < 0.01), and the absolute proportion of patients who reported smoking decreased (10% vs 15%; MD, -5%; 95% CI, -8% to -2%; P < 0.01) among DHI participants with available data. No adverse events were reported. CONCLUSIONS: The addition of a DHI-enhanced remote CR program was delivered in 16% of referred veterans and associated with improved CR access, markers of cardiovascular risk, and healthy behaviors in this real-world study. These findings support the continued implementation of DHIs for remote CR in real-world clinical settings. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT02791685 (07/06/2016).

Pseudo-Wellens syndrome, acute pancreatitis, and an anomalous coronary artery: a case report.

BACKGROUND: Chest pain associated with transient electrocardiogram changes mimicking an acute myocardial infarction have been described in acute pancreatitis. These ischemic electrocardiogram changes can present a diagnostic dilemma, especially when patients present with concurrent angina pectoris and epigastric pain warranting noninvasive or invasive imaging studies. CASE PRESENTATION: A 45-year-old African-American man with a history of alcohol use disorder presented to the emergency department of our institution with 36 hours of concurrent epigastric pain and left-sided chest pain radiating to his left arm and associated with nausea and dyspnea. On physical examination, he was afebrile; his blood pressure was elevated; and he had epigastric tenderness. His laboratory test results were significant for hypokalemia, normal troponin, and elevated serum lipase and amylase levels. Serial electrocardiograms for persistent chest pain showed ST-segment elevations with dynamic T-wave changes in the right precordial electrocardiogram leads, consistent with Wellens syndrome. He was immediately taken to the cardiac catheterization laboratory, where selective coronary angiography showed normal coronary arteries with an anomalous origin of the right coronary artery from the opposite sinus. Given his elevated lipase and amylase levels, the patient was treated for acute alcohol-induced pancreatitis with intravenous fluids and pain control. His chest pain and ischemic electrocardiogram changes resolved within 24 hours of admission, and coronary computed tomography angiography showed an interarterial course of the right coronary artery without high-risk features. CONCLUSIONS: Clinicians may consider deferring immediate cardiac catheterization and attribute electrocardiogram changes to acute pancreatitis in patients presenting with angina pectoris and acute pancreatitis if confirmed by normal cardiac enzymes and elevated levels of lipase and amylase. However, when clinical signs and electrocardiogram findings are highly suggestive of myocardial ischemia/injury, immediate noninvasive coronary computed tomography angiography may be the best approach to make an early diagnosis.

Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death.

BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. METHODS AND RESULTS: C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden's index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. CONCLUSIONS: SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors.

RATIONALE: We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors (RFs). OBJECTIVE: Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared with aging with RFs or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age. METHODS AND RESULTS: In 2792 adult subjects, 498 were free of RFs (smoking, diabetes mellitus, hypertension, or hyperlipidemia), 1036 subjects had 1 to 2 RF, and 1253 had ≥3 RFs or CVD. PC were enumerated by flow cytometry as CD45(med+) mononuclear cells expressing CD34 and subsets coexpressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 epitopes. Younger age, male sex, and larger body size correlated with higher PC counts (P<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (P<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (P≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts. CONCLUSIONS: Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization, whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.

Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease.

BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

Cerebral Oximetry as a Real-Time Monitoring Tool to Assess Quality of In-Hospital Cardiopulmonary Resuscitation and Post Cardiac Arrest Care.

BACKGROUND: Regional cerebral oxygen saturation (rSO2) as assessed by near infrared frontal cerebral spectroscopy decreases in circulatory arrest and increases with high-quality cardiopulmonary resuscitation. We hypothesized that higher rSO2 during cardiopulmonary resuscitation and after return of spontaneous circulation (ROSC) would predict survival to discharge and neurological recovery. METHODS AND RESULTS: This prospective case series included patients experiencing in-hospital cardiac arrest. Cerebral oximetry was recorded continuously from initiation of resuscitation until ROSC and up to 48 hours post-arrest. Relationships between oximetry data during these time periods and outcomes of resuscitation survival and survival to discharge were analyzed. The cohort included 27 patients. Nineteen (70.3%) achieved ROSC, and 8 (29.6%) survived to discharge. Median arrest duration was 20.8 minutes (range=8 to 74). There was a significant difference in rSO2 between resuscitation survivors and resuscitation nonsurvivors at initiation of the resuscitative efforts (35% versus 17.5%, P=0.03) and during resuscitation (36% versus 15%, P=0.0008). No significant association was observed between rSO2 at ROSC or during the post-arrest period and survival to discharge. Among patients who survived to discharge, there was no association between cerebral performance category and rSO2 at ROSC, during resuscitation, or post-arrest. CONCLUSIONS: Higher rSO2 levels at initiation of resuscitation and during resuscitation are associated with resuscitation survival and may reflect high-quality cardiopulmonary resuscitation. However, in this small series, rSO2 was not predictive of good neurological outcome. Larger studies are needed to determine whether this monitoring modality can be used to improve clinical outcomes.

Plasma stromal cell-derived factor 1α/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease.

OBJECTIVE: Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). METHODS: 785 patients aged: 63 ± 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. RESULTS: The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 × 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. CONCLUSION: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.

Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.

RATIONALE: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. OBJECTIVES: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. METHODS AND RESULTS: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (ß=-0.92, P=0.043 and ß=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (ß=-1.25, P=0.020 and ß=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors. CONCLUSIONS: Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.

AWARE-AWAreness during REsuscitation-a prospective study.

BACKGROUND: Cardiac arrest (CA) survivors experience cognitive deficits including post-traumatic stress disorder (PTSD). It is unclear whether these are related to cognitive/mental experiences and awareness during CPR. Despite anecdotal reports the broad range of cognitive/mental experiences and awareness associated with CPR has not been systematically studied. METHODS: The incidence and validity of awareness together with the range, characteristics and themes relating to memories/cognitive processes during CA was investigated through a 4 year multi-center observational study using a three stage quantitative and qualitative interview system. The feasibility of objectively testing the accuracy of claims of visual and auditory awareness was examined using specific tests. The outcome measures were (1) awareness/memories during CA and (2) objective verification of claims of awareness using specific tests. RESULTS: Among 2060 CA events, 140 survivors completed stage 1 interviews, while 101 of 140 patients completed stage 2 interviews. 46% had memories with 7 major cognitive themes: fear; animals/plants; bright light; violence/persecution; deja-vu; family; recalling events post-CA and 9% had NDEs, while 2% described awareness with explicit recall of 'seeing' and 'hearing' actual events related to their resuscitation. One had a verifiable period of conscious awareness during which time cerebral function was not expected. CONCLUSIONS: CA survivors commonly experience a broad range of cognitive themes, with 2% exhibiting full awareness. This supports other recent studies that have indicated consciousness may be present despite clinically undetectable consciousness. This together with fearful experiences may contribute to PTSD and other cognitive deficits post CA.

Sex and age differences in the association of depression with obstructive coronary artery disease and adverse cardiovascular events.

BACKGROUND: Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women. METHODS AND RESULTS: We examined 3237 patients undergoing coronary angiography for evaluation of CAD and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9, and CAD burden was dichotomized based on its presence or absence. After multivariable adjustment for CAD risk factors, depressive symptoms predicted CAD presence in women aged ≤ 55 years (odds ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤ 55 years (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years and women aged >55 years, with P=0.02 for the depression-sex interaction and P=0.02 for depression-sex-age interaction. CONCLUSIONS: Among patients with suspected or established CAD, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.

Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (ß=9.53; P<0.001), Ln glutathione (ß=-5.4; P=0.002), and Eh glutathione (ß=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (ß=6.56; P=0.007), mitral regurgitation (ß=4.52; P<0.001), statin use (ß=-3.39; P=0.03), left ventricular ejection fraction (ß=-0.26; P=0.003), and age (ß=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

Factors affecting mechanical properties of biomass pellet from compost.

Effectiveness of a densification process to create strong and durable bonding in pellets can be determined by testing the mechanical properties such as compressive strength (CS) and durability. Mechanical properties of pellet from composted municipal solid waste were determined at different raw material and densification conditions. Ground compost samples were compressed with three levels of moisture content (35%, 40% and 45% (wb)), piston compaction speed (2, 6 and 10 mm/s), die length (8, 10 and 12mm) and raw material particle size (0.3, 0.9 and 1.5mm) into cylindrical pellets utilizing opened-end dies under axial stress from a vertical piston applied by a hydraulic press. The effects of independent variables on mechanical properties were determined using response surface methodology based on Box-Behnken design (BBD). All independent variables affected the durability significantly. However, different piston speed and die length not produce any significant difference on CS of pellets. Also in this research the electron photography method was used to identify the binding mechanism of compost particles.

Myocardial ischemia during mental stress: role of coronary artery disease burden and vasomotion.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress-induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes. METHODS AND RESULTS: Patients with angiographically documented CAD underwent 99mTc-sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The severity and extent of CAD were quantified using the Gensini and Sullivan scores. Peripheral arterial tonometry (Itamar Inc) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared with baseline. Measurements were made in a discovery sample (n = 225) and verified in a replication sample (n = 159). In the pooled (n = 384) sample, CAD severity and extent scores were not significantly different between those with and without MSIMI, whereas they were greater in those with compared with those without PSIMI (P < 0.04 for all). The peripheral arterial tonometry ratio was lower in those with compared with those without MSIMI (0.55 ± 0.36 versus 0.76 ± 0.52, P = 0.009). In a multivariable analysis, the peripheral arterial tonometry ratio was the only independent predictor of MSIMI (P = 0.009), whereas angiographic severity and extent of CAD independently predicted PSIMI. CONCLUSIONS: The degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSIMI. Varying causes of MSIMI compared with PSIMI may require different therapeutic interventions that require further study.

Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.

OBJECTIVE: Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress. METHODS: Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine. RESULTS: Overall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73). CONCLUSION: In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.

Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis.

OBJECTIVES: This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. BACKGROUND: Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. METHODS: We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. RESULTS: We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. CONCLUSIONS: The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

Coronary angiographic scoring systems: an evaluation of their equivalence and validity.

BACKGROUND: Multiple scoring systems have been devised to quantify angiographic coronary artery disease (CAD) burden, but it is unclear how these scores relate to each other and which scores are most accurate. The aim of this study was to compare coronary angiographic scoring systems (1) with each other and (2) with intravascular ultrasound (IVUS)-derived plaque burden in a population undergoing angiographic evaluation for CAD. METHODS: Coronary angiographic data from 3600 patients were scored using 10 commonly used angiographic scoring systems and interscore correlations were calculated. In a subset of 50 patients, plaque burden and plaque area in the left anterior descending coronary artery were quantified using IVUS and correlated with angiographic scores. RESULTS: All angiographic scores correlated with each other (range for Spearman coefficient [ρ] 0.79-0.98, P < .0001); the 2 most widely used scores, Gensini and CASS-70, had a ρ = 0.90 (P < .0001). All scores correlated significantly with average plaque burden and plaque area by IVUS (range ρ 0.56-0.78, P < .0001 and 0.43-0.62, P < .01, respectively). The CASS-50 score had the strongest correlation (ρ 0.78 and 0.62, P < .0001) and the Duke Jeopardy score the weakest correlation (ρ 0.56 and 0.43, P < .01) with plaque burden and area, respectively. CONCLUSIONS: Angiographic scoring systems are strongly correlated with each other and with atherosclerotic plaque burden. Scoring systems therefore appear to be a valid estimate of CAD plaque burden.