Coronary risk equivalence of diabetes assessed by SPECT-MPI.

BACKGROUND: Several publications and guidelines designate diabetes mellitus (DM) as a coronary artery disease (CAD) risk equivalent. The aim of this investigation was to examine DM cardiac risk equivalence from the perspective of stress SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: We examined cardiovascular outcomes (cardiac death or nonfatal MI) of 17,499 patients referred for stress SPECT-MPI. Patients were stratified into four categories: non-DM without CAD, non-DM with CAD, DM without CAD, and DM with CAD, and normal or abnormal perfusion. Cardiac events occurred in 872 (5%), with event-free survival best among non-DM without CAD, worst in DM with CAD, and intermediate in DM without CAD, and non-DM with CAD. After multivariate adjustment, risk remained comparable between DM without CAD and non-DM with CAD [AHR 1.0 (95% CI 0.84-1.28), P =0.74]. Annualized event rates for normal subjects were 1.4% and 1.6% for non-DM with CAD and DM without CAD, respectively (P = 0.48) and 3.5% (P = 0.95) for both abnormal groups. After multivariate adjustment, outcomes were comparable within normal [AHR 1.4 (95% CI 0.98-1.96) P = 0.06] and abnormal [AHR 1.1 (95% CI 0.83-1.50) P = 0.49] MPI. CONCLUSIONS: Diabetic patients without CAD have comparable risk of cardiovascular events as non-diabetic patients with CAD after stratification by MPI results. These findings support diabetes as a CAD equivalent and suggest that MPI provides additional prognostic information in such patients.

The effect of high-dose atorvastatin on neural activity and cognitive function.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

The burden of behavioral risk factors for cardiovascular disease in Europe. A significant prevention deficit.

OBJECTIVE: The study objective was to assess the burden of major cardiovascular disease (CVD) behavioral risk factors (BRFs) (i.e., smoking, excess body weight, physical inactivity, risky alcohol consumption) among individuals in the community with and without CVD history. METHODS: For the current study, a subset of the data from the Survey of Health, Ageing and Retirement in Europe (SHARE) was analyzed, which were collected from 26,743 individuals aged 50+ years old, during the 1st wave of SHARE in 2004/05 in eleven European countries. RESULTS: Among those with CVD, there is a statistically significant higher percentage of inactive individuals (81.4% vs. 69.5 among those without CVD), and of individuals with excess body weight (64.3%) or obese (21.6%). Patients with CVD had a lower prevalence of smoking and risky alcohol consumption in most countries, whereas the prevalence of high body weight and physical inactivity was higher in CVD patients compared to individuals without CVD in almost all countries. More than half of the population has at least two BRFs, with a significantly higher prevalence of multiple BRFs among those diagnosed with CVD. CONCLUSION: Study findings suggest that a significant burden of behavioral risk factors for CVD remains in the population overall but also among patients diagnosed with CVD. Given the significant prevalence of BRFs, the prevention benefits would be immense for all stakeholders involved and negligence would be perilous.

Cardiovascular risk stratification in diabetic patients following stress single-photon emission-computed tomography myocardial perfusion imaging: the impact of achieved exercise level.

BACKGROUND: Previous studies have demonstrated that diabetic patients undergoing exercise stress single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) have significantly lower cardiac events when compared to the diabetic patients undergoing pharmacologic stress SPECT MPI across all perfusion categories. However, there are limited data on the level of exercise achieved during exercise SPECT MPI among diabetic patients and its impact on cardiovascular outcomes. METHODS: We retrospectively analyzed 14,849 consecutive patients (3,654 diabetics and 11,195 non-diabetics) undergoing exercise stress, combined exercise and pharmacologic stress, and pharmacologic stress SPECT MPI from 1996 to 2005 at a single tertiary care center. Diabetic and non-diabetic patients were categorized into 3 groups based on the metabolic equivalents (METs) achieved: ≥5 METs, <5 METs, and pharmacologic stress groups. All studies were interpreted using the 17-segment ASNC model. The presence, extent, severity of perfusion defects were calculated using the summed stress score (SSS), and patients were classified into normal (SSS < 4), mildly abnormal (SSS 4-8), and moderate-severely abnormal (SSS > 8) categories. Annualized event rates (AER) for the composite end point of non-fatal myocardial infarction and cardiac death were calculated over a mean follow-up period of 2.4 ± 1.4 years with a maximum of 6 years. RESULTS: In moderate-severe perfusion abnormality (SSS > 8) category, diabetic patients who were able to achieve ≥5 METs had significantly lower AER compared to diabetic patients who were unable to achieve ≥5 METs (3% vs 5.5%, P = .04), and non-diabetic patients unable to achieve ≥5 METs (3% vs 4.8%, P < .001). Diabetic patients who achieved a high workload of ≥10 METs had a very low AER of 0.9%. Diabetic patients, who attempted exercise but were unable to achieve ≥5 METs, still had significantly lower AER than diabetics undergoing pharmacologic stress MPI across all perfusion categories [1.5% vs 3.2%, P = .006 (SSS < 4); 2.5% vs 4.9%, P = .032 (SSS 4-8); 5.5% vs 10.3%, P = .003 (SSS > 8)]. After adjustment for cardiovascular risk factors, the percentage decrease in cardiac event rate for every 1-MET increment in exercise capacity was 10% in the overall cohort, 12% in diabetic group, and 8% in non-diabetic group. CONCLUSIONS: Despite significant perfusion defects, diabetic patients who achieve ≥5 METs during stress SPECT MPI have significantly reduced risk for future cardiac events. Diabetic patients who achieve ≥10 METs have a very low annualized event rate. These findings support that exercise capacity obtained during SPECT MPI is a surrogate for outcomes among diabetic patients undergoing nuclear stress testing.

Risk stratification using line source attenuation correction with rest/stress Tc-99m sestamibi SPECT myocardial perfusion imaging.

BACKGROUND: Although line source attenuation correction (AC) in SPECT MPI studies improves diagnostic accuracy, its prognostic value is less understood. METHODS: Consecutive patients (n = 6,513) who underwent rest/stress AC ECG-gated SPECT MPI were followed for cardiac death or non-fatal myocardial infarction (MI). A 17-segment model and AC summed stress score (SSS) were used to classify images. RESULTS: Of the 6,513 patients, cardiac death or non-fatal MI occurred in 267 (4.1%), over 2.0 ± 1.4 years. The AC-SSS in patients with a cardiac event (5.6 ± 7.8) was significantly higher than in those without (1.9 ± 4.6, P < .001). The annualized cardiac event rate in patients with an AC-SSS 1-3 (3.6%) was significantly higher than in those with an AC-SSS = 0 (1.1%, P < .001) but similar to that in those with an AC-SSS 4-8 (2.9%, P = .4). Accordingly, patients were classified to AC-SSS = 0, 1-8, and >8 with annualized cardiac event rates of 1.1%, 3.2%, and 8.5%, respectively (P < .0001). In multivariate analysis, an AC-SSS 1-8 and >8 emerged as independent predictors of cardiac events (P < .02 and P < .0001, respectively). CONCLUSION: Rest/stress ECG-gated SPECT MPI with line source AC provides highly effective and incremental risk stratification for future cardiac events.

Risk stratification among diabetic patients undergoing stress myocardial perfusion imaging.

BACKGROUND: Previous studies have suggested that diabetic patients undergoing single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) are at greater risk for cardiac events than non-diabetic patients with both normal and abnormal imaging results. However, the impact of stress modality on outcomes in this patient group has not been examined. METHODS: The data on all patients undergoing exercise stress or vasodilator stress SPECT MPI from 1996 to 2005 were reviewed. After excluding patients based on our predefined criteria, we subcategorized the study population into diabetic patients and non-diabetic patients. Among the diabetic patients, we identified patients with known coronary artery disease (CAD) and no known CAD. All studies were interpreted using the 17-segment ASNC model. The presence, extent, and severity of perfusion defects were calculated using the summed stress score (SSS), and patients were classified into normal (SSS < 4), mildly abnormal (SSS 4-8), and moderate-severely abnormal (SSS > 8) categories. The annualized cardiac event rate including cardiac death and non-fatal myocardial infarction was calculated over a mean follow-up period of 2.4 ± 1.4 years with a maximum of 6 years. RESULTS: The cardiac event rate was statistically significantly lower in diabetic patients undergoing exercise stress MPI when compared to the diabetic patients undergoing pharmacological stress MPI across all three perfusion categories (1.3% vs 3.4%, 2.3% vs 5.7%, 4.2% vs 10.7%, respectively). Diabetic patients with no known CAD, who underwent exercise stress MPI had significantly lower cardiac events across all three perfusion categories as compared to the remainder of the diabetic population. Ability to perform exercise stress test was the strongest multivariate predictor of favorable outcome, whereas ejection fraction < 50%, abnormal perfusion imaging on SPECT MPI, and increasing age stood out as independent predictors of adverse outcome in the diabetic patients. Within the abnormal perfusion category, the annualized cardiac event rate among patients undergoing exercise stress SPECT MPI was not statistically different between the diabetic and non-diabetic cohorts. CONCLUSION: Diabetic patients undergoing exercise SPECT MPI have a significantly better prognosis than those undergoing pharmacological stress, more similar to patients without diabetes. In patients with diabetes exercise stress test MPI identifies low risk patients and provides precise risk stratification.

The clinical value of single photon emission computed tomography myocardial perfusion imaging in cardiac risk stratification of very elderly patients (≥80 years) with suspected coronary artery disease.

BACKGROUND: The role of single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in cardiac evaluation of the very elderly patients is unclear. We investigated the clinical value of SPECT MPI in very elderly patients (≥80 years) with suspected coronary artery disease (CAD) as well as in comparison to younger patients. METHODS AND RESULTS: A retrospective analysis of prospectively collected data from 8,864 patients [1,093 patients ≥80 years (very elderly), 3,369 patients 65-79 years (elderly), and 4,402 patients 50-64 years (middle-aged)] with suspected CAD who underwent exercise and/or pharmacologic stress testing with SPECT MPI between 1996 and 2005 was performed. Clinical and SPECT MPI characteristics, cardiac event rates, early (≤60 days) cardiac catheterization and revascularization rates of very elderly patients were compared to that of younger patients. Mean follow-up for cardiac events (cardiac death or non-fatal myocardial infarction) was 1.9 ± 0.9 years. Very elderly patients with moderate to severely abnormal SSS had a significantly higher annualized cardiac event rate than those with mildly abnormal or normal study (9.6% vs 3.4% and 2.5% respectively, P < .001). Across all categories of SSS, very elderly patients had a significantly higher cardiac event rate as compared to younger patients (P < .001). Early cardiac catheterization and revascularization referrals in very elderly patients increased as a function of severity of ischemia on SPECT MPI (P < .001), although these referral rates were significantly lower in very elderly patients with mild to moderate and severe ischemia as compared to younger patients (P < .05). CONCLUSIONS: In very elderly patients (≥80 years) with suspected CAD, SPECT MPI has prognostic and incremental value in the noninvasive cardiovascular assessment for risk stratification and may influence medical decisions.

Impact of coronary artery calcium testing on patient management.

BACKGROUND: Coronary artery calcium (CAC) scoring can identify individuals who may benefit from aggressive prevention therapies. However, there is a paucity of contemporary data on the impact of CAC testing on patient management. METHODS: Retrospective cohort study of adults who underwent CAC testing at Brigham and Women's Hospital between 2015 and 2019. Information on baseline medications, follow-up medications, lifestyle modification, and downstream cardiovascular testing within one-year post-CAC were obtained from electronic health records. RESULTS: Of the 839 patients with available baseline and follow-up data, 376 (45%) had a CAC â€‹= â€‹0, 289 (34%) had CAC â€‹= â€‹1-99, and 174 (21%) had CAC≥100. The mean age at time of CAC testing was 59 â€‹± â€‹9.7 years. Patients with higher CAC scores were more likely to be male, have diabetes and hypertension, and have higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol. A non-zero CAC score was associated with initiation of aspirin (41% increase, p â€‹< â€‹0.001), anti-hypertensives (9% increase, p â€‹= â€‹0.031), and lipid-lowering therapies (114% increase, p â€‹< â€‹0.001), whereas CAC â€‹= â€‹0 was not. Among individuals with CAC≥100, 75% were started on new or more intense lipid-lowering therapy. Higher calcium scores correlated with increased physician recommendations for diet (p â€‹= â€‹0.008) and exercise (p â€‹= â€‹0.004). The proportion of cardiovascular downstream testing following CAC was 9.1%, and the majority of patients who underwent additional testing post-CAC had CAC scores ≥100. CONCLUSION: Approximately half of individuals referred for CAC testing had evidence of calcified coronary plaque, and of those who had significant calcifications (CAC≥100), nearly 90% were prescribed lipid-lowering therapies post-CAC. Rates of downstream non-invasive testing were low and such testing was mostly performed in patients who had at least moderate CAC.

Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women.

This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL), N(G)-monomethyl-L-arginine (L-NMMA), and ketorolac (KETO) + L-NMMA in healthy younger men (M; n = 8) and women (W; n = 8). In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and L-NMMA + KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). L-NMMA reduced %FMD similarly and modestly (P = 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 ± 3.8 to 7.6 ± 4.7%; P = 0.03) with no further effect of KETO (P = 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for l-NMMA and KETO + l-NMMA were insignificant (all P > 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After l-NMMA infusion, subjects exhibited both reduced (n = 14; range: 11 to 78% decrease) and augmented (n = 2; range: 1 to 96% increase) %FMD. Following KETO + l-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia.

Association of Socioeconomic Disadvantage With Long-term Mortality After Myocardial Infarction: The Mass General Brigham YOUNG-MI Registry.

Importance: Socioeconomic disadvantage is associated with poor health outcomes. However, whether socioeconomic factors are associated with post-myocardial infarction (MI) outcomes in younger patient populations is unknown. Objective: To evaluate the association of neighborhood-level socioeconomic disadvantage with long-term outcomes among patients who experienced an MI at a young age. Design, Setting, and Participants: This cohort study analyzed patients in the Mass General Brigham YOUNG-MI Registry (at Brigham and Women's Hospital and Massachusetts General Hospital in Boston, Massachusetts) who experienced an MI at or before 50 years of age between January 1, 2000, and April 30, 2016. Each patient's home address was mapped to the Area Deprivation Index (ADI) to capture higher rates of socioeconomic disadvantage. The median follow-up duration was 11.3 years. The dates of analysis were May 1, 2020, to June 30, 2020. Exposures: Patients were assigned an ADI ranking according to their home address and then stratified into 3 groups (least disadvantaged group, middle group, and most disadvantaged group). Main Outcomes and Measures: The outcomes of interest were all-cause and cardiovascular mortality. Cause of death was adjudicated from national registries and electronic medical records. Cox proportional hazards regression modeling was used to evaluate the association of ADI with all-cause and cardiovascular mortality. Results: The cohort consisted of 2097 patients, of whom 2002 (95.5%) with an ADI ranking were included (median [interquartile range] age, 45 [42-48] years; 1607 male individuals [80.3%]). Patients in the most disadvantaged neighborhoods were more likely to be Black or Hispanic, have public insurance or no insurance, and have higher rates of traditional cardiovascular risk factors such as hypertension and diabetes. Among the 1964 patients who survived to hospital discharge, 74 (13.6%) in the most disadvantaged group compared with 88 (12.6%) in the middle group and 41 (5.7%) in the least disadvantaged group died. Even after adjusting for a comprehensive set of clinical covariates, higher neighborhood disadvantage was associated with a 32% higher all-cause mortality (hazard ratio, 1.32; 95% CI, 1.10-1.60; P = .004) and a 57% higher cardiovascular mortality (hazard ratio, 1.57; 95% CI, 1.17-2.10; P = .003). Conclusions and Relevance: This study found that, among patients who experienced an MI at or before age 50 years, socioeconomic disadvantage was associated with higher all-cause and cardiovascular mortality even after adjusting for clinical comorbidities. These findings suggest that neighborhood and socioeconomic factors have an important role in long-term post-MI survival.

Perceptions on Diversity in Cardiology: A Survey of Cardiology Fellowship Training Program Directors.

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief that diversity is a driver of excellence in health care, only 26% could quote 1 to 2 references to support this statement. Sixty-three percent of respondents agreed that "our program is diverse already so diversity does not need to be increased." Only 6% of respondents listed diversity as a top 3 priority when creating the cardiovascular fellowship rank list. Conclusions These findings suggest that while program directors generally believe that diversity enhances quality, they are less familiar with the literature that supports that contention and they may not share a unified definition of "diversity." This may result in diversity enhancement having a low priority. The authors propose several strategies to engage fellowship training program directors in efforts to diversify cardiology fellowship training programs.

Diabetes Is Associated With Worse Long-term Outcomes in Young Adults After Myocardial Infarction: The Partners YOUNG-MI Registry.

OBJECTIVE: We sought to determine the prevalence of diabetes and associated cardiovascular outcomes in a contemporary cohort of young individuals presenting with their first myocardial infarction (MI) at age ≤50 years. RESEARCH DESIGN AND METHODS: We retrospectively analyzed records of patients presenting with a first type 1 MI at age ≤50 years from 2000 to 2016. Diabetes was defined as a hemoglobin A1c ≥6.5% (48 mmol/mol) or a documented diagnosis of or treatment for diabetes. Vital status was ascertained for all patients, and cause of death was adjudicated. RESULTS: Among 2,097 young patients who had a type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), diabetes was present in 416 (20%), of whom 172 (41%) were receiving insulin. Over a median follow-up of 11.2 years (interquartile range 7.3-14.2 years), diabetes was associated with a higher all-cause mortality (hazard ratio 2.30; P < 0.001) and cardiovascular mortality (2.68; P < 0.001). These associations persisted after adjusting for baseline covariates (all-cause mortality: 1.65; P = 0.008; cardiovascular mortality: 2.10; P = 0.004). CONCLUSIONS: Diabetes was present in 20% of patients who presented with their first MI at age ≤50 years and was associated with worse long-term all-cause and cardiovascular mortality. These findings highlight the need for implementing more aggressive therapies aimed at preventing future adverse cardiovascular events in this population.

Comparative use of radionuclide stress testing, coronary artery calcium scanning, and noninvasive coronary angiography for diagnostic and prognostic cardiac assessment.

Noninvasive cardiac imaging has undergone a recent resurgence with the development of new approaches for imaging coronary atherosclerosis. Non-contrast computed tomography (CT) for imaging the extent of coronary artery calcification (CAC) and contrast CT for noninvasive coronary angiography (CTA) are developments with a growing evidence base regarding risk assessment and the diagnosis of obstructive coronary disease. This review discusses the role of CAC for risk assessment of asymptomatic individuals and for the use of coronary CTA in symptomatic patients. By comparison, gated myocardial perfusion scintigraphy (MPS) is a well-established noninvasive imaging modality that is a core element in evaluation of patients with stable chest pain syndromes. Stress MPS is the most commonly used stress imaging technique for patients with suspected or known coronary disease. In contrast to the nascent evidence noted with coronary CTA, MPS has a robust evidence base, including the support of numerous clinical guidelines. We highlight the current evidence supporting the diagnostic accuracy and risk stratification data for MPS for symptomatic patients with known or suspected coronary artery disease. It is likely that assessing the extent of atherosclerosis using CAC or coronary CTA will become an increasing part of mainstream cardiovascular imaging practices. In some patients, further ischemia testing with MPS will be required. Similarly, in some patients referred for MPS, anatomic definition of atherosclerosis using CAC by CT may be appropriate. Thus, this review also provides a synopsis of the available literature on imaging that integrates both CT and MPS in combined strategies for the assessment of atherosclerotic and obstructive coronary disease burden. We also propose possible risk-based strategies through which imaging might be used to identifying candidates for more intensive prevention and risk factor modification strategies as well as those who would benefit from referral to coronary angiography and revascularization.