Incidence and prognostic significance of newly-diagnosed atrial fibrillation among older U.S. veterans hospitalized with COVID-19.

Most prior studies on the prognostic significance of newly-diagnosed atrial fibrillation (AF) in COVID-19 did not differentiate newly-diagnosed AF from pre-existing AF. To determine the association between newly-diagnosed AF and in-hospital and 30-day mortality among regular users of Veterans Health Administration using data linked to Medicare. We identified Veterans aged ≥ 65 years who were hospitalized for ≥ 24 h with COVID-19 from 06/01/2020 to 1/31/2022 and had ≥ 2 primary care visits within 24 months prior to the index hospitalization. We performed multivariable logistic regression analyses to estimate adjusted risks, risk differences (RD), and odds ratios (OR) for the association between newly-diagnosed AF and the mortality outcomes adjusting for patient demographics, baseline comorbidities, and presence of acute organ dysfunction on admission. Of 23,299 patients in the study cohort, 5.3% had newly-diagnosed AF, and 29.2% had pre-existing AF. In newly-diagnosed AF adjusted in-hospital and 30-day mortality were 16.5% and 22.7%, respectively. Newly-diagnosed AF was associated with increased mortality compared to pre-existing AF (in-hospital: OR 2.02, 95% confidence interval [CI] 1.72-2.37; RD 7.58%, 95% CI 5.54-9.62) (30-day: OR 1.86; 95% CI 1.60-2.16; RD 9.04%, 95% CI 6.61-11.5) or no AF (in-hospital: OR 2.24, 95% CI 1.93-2.60; RD 8.40%, 95% CI 6.44-10.4) (30-day: 2.07, 95% CI 1.80-2.37; RD 10.2%, 95% CI 7.89-12.6). There was a smaller association between pre-existing AF and the mortality outcomes. Newly-diagnosed AF is an important prognostic marker for patients hospitalized with COVID-19. Whether prevention or treatment of AF improves clinical outcomes in these patients remains unknown.

Cardiovascular Disease Risk Assessment Using Traditional Risk Factors and Polygenic Risk Scores in the Million Veteran Program.

Importance: Primary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation. Objective: To determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population. Design, Setting, and Participants: This was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023. Exposures: PRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status. Main Outcomes and Measures: Incident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events. Results: A total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, -0.07% to 3.30%). Conclusions and Relevance: Study results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.

Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: Results from the Patient and Provider Assessment of Lipid Management (PALM) registry.

BACKGROUND: Adherence to guideline-recommended statin recommendations in the United States is suboptimal. Patients' likelihood to be treated according to guidelines may vary by the practice in which they are treated. METHODS: Variation in the use of statin therapy in 5445 patients, with known or at high risk for atherosclerotic cardiovascular disease (ASCVD) and meeting a statin treatment indication, was examined across 74 US Patient and Provider Assessment of Lipid Management (PALM) Registry clinics. Multivariable generalized linear mixed modeling was used to determine the median odds ratio (MOR) for statin use and 2013 American College of Cardiology/American Heart Association guideline-recommended statin intensity by practice. MOR quantifies between-practice variation by comparing the odds of receiving guideline-recommended statin treatment in a patient from a randomly selected practice with a similar patient from another random practice. Risk-adjusted low-density lipoprotein cholesterol (LDL-C) control (<100 and <70 mg/dL) was compared among practice tertiles based on percentage of eligible patients receiving recommended statin intensity. RESULTS: Among 74 practices (43.2% cardiology) comprised of 300 healthcare providers enrolling 5445 patients (56.2% with ASCVD), statin use at the guideline-recommended intensity at practices varied widely (12.7-71.4%; adjusted MOR 1.45, 95% confidence interval [CI] 1.35-1.64). Results were consistent when evaluated for any statin use overall (adjusted MOR 1.75, 95% CI 1.48-1.99) and when stratified by primary versus secondary prevention patients. Relative to practices with lowest or mid-tertile statin use of statins, highest tertile clinics were more frequently cardiology practices (68.0% vs 48.0% vs 12.5%, P < .001). Compared with lowest tertile clinics, patients at highest tertile clinics were more likely to achieve LDL-C <70 mg/dL (adjusted odds ratio [OR] 1.49, 95% CI 1.08-2.04) and <100 mg/dL (adjusted OR 1.78, 95% CI 1.41-2.25). CONCLUSIONS: US clinics varied widely in their adherence to guideline recommendations for statin therapy, which contributed to significant differences in LDL-C levels.

Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published. METHODS: We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes. CONCLUSIONS: In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.

Association of Patient Perceptions of Cardiovascular Risk and Beliefs on Statin Drugs With Racial Differences in Statin Use: Insights From the Patient and Provider Assessment of Lipid Management Registry.

Importance: African American individuals face higher atherosclerotic cardiovascular disease risk than white individuals; reasons for these differences, including potential differences in patient beliefs regarding preventive care, remain unknown. Objective: To evaluate differences in statin use between white and African American patients and identify the potential causes for any observed differences. Design, Setting, and Participants: Using the 2015 Patient and Provider Assessment of Lipid Management (PALM) Registry data, we compared statin use and dosing between African American and white outpatient adults who were potentially eligible for primary or secondary prevention statins. A total of 138 US community health care practices contributed to the data. Data analysis was conducted from March 2017 to May 2018. Main Outcomes and Measures: Primary outcomes were use and dosing of statin therapy according to the 2013 American College of Cardiology/American Heart Association guideline by African American or white race. Secondary outcomes included lipid levels and patient-reported beliefs. Poisson regression was used to evaluate the association between race and statin undertreatment, a category combining people who were not taking a statin or those taking a dose intensity lower than recommended. Results: A total of 5689 patients (806 [14.2%] African American) in the PALM registry were eligible for statin therapy. African American individuals were less likely than white individuals to be treated with a statin (570/807 [70.6%] vs 3654/4883 [74.8%]; P = .02). Among those treated, African American patients were less likely than white patients to receive a statin at guideline-recommended intensity (269 [33.3%] vs 2145 [43.9%], respectively; P < .001; relative risk, 1.07 [95% CI, 1.00-1.15]; P = .05, after adjustment for demographic and clinical factors). The median (interquartile range) low-density lipoprotein cholesterol levels of patients receiving treatment were higher among African American than white individuals (97.0 [76.0-121.0] mg/dL vs 85.0 [68.0-105.0] mg/dL; P < .001). African American individuals were less likely than white individuals to believe statins were safe (292 [36.2%] vs 2800 [57.3%]; P < .001) or effective (564 [70.0%] vs 3635 [74.4%]; P = .008) and were less likely to trust their clinician (663 [82.3%] vs 4579 [93.8%]; P < .001). Group differences in statin undertreatment were not significant after adjusting for demographic, clinical, and clinician factors, socioeconomic status, and patient beliefs (final adjusted relative risk, 1.03 [95% CI 0.96-1.11]; P = .35). Conclusions and Relevance: African American individuals were less likely to receive guideline-recommended statin therapy. Demographic, clinical, socioeconomic, belief-related, and clinician differences contributed to observed differences and represent potential targets for intervention.

10-Year Resource Utilization and Costs for Cardiovascular Care.

BACKGROUND: Cardiovascular disease (CVD) imparts a heavy economic burden on the U.S. health care system. Evidence regarding the long-term costs after comprehensive CVD screening is limited. OBJECTIVES: This study calculated 10-year health care costs for 6,814 asymptomatic participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a registry sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health. METHODS: Cumulative 10-year costs for CVD medications, office visits, diagnostic procedures, coronary revascularization, and hospitalizations were calculated from detailed follow-up data. Costs were derived by using Medicare nationwide and zip code-specific costs, inflation corrected, discounted at 3% per year, and presented in 2014 U.S. dollars. RESULTS: Risk factor prevalence increased dramatically and, by 10 years, diabetes, hypertension, and dyslipidemia was reported in 19%, 57%, and 53%, respectively. Self-reported symptoms (i.e., chest pain or shortness of breath) were common (approximately 40% of enrollees). At 10 years, approximately one-third of enrollees reported having an echocardiogram or exercise test, whereas 7% underwent invasive coronary angiography. These utilization patterns resulted in 10-year health care costs of $23,142. The largest proportion of costs was associated with CVD medication use (78%). Approximately $2 of every $10 were spent for outpatient visits and diagnostic testing among the elderly, obese, those with a high-sensitivity C-reactive protein level >3 mg/l, or coronary artery calcium score (CACS) ≥400. Costs varied widely from <$7,700 for low-risk (Framingham risk score <6%, 0 CACS, and normal glucose measurements at baseline) to >$35,800 for high-risk (persons with diabetes, Framingham risk score ≥20%, or CACS ≥400) subgroups. Among high-risk enrollees, CVD costs accounted for $74 million of the $155 million consumed by MESA participants. CONCLUSIONS: Longitudinal patterns of health care resource use after screening revealed new evidence on the economic burden of treatment and testing patterns not previously reported. Maintenance of a healthy population has the potential to markedly reduce the economic burden of CVD among asymptomatic individuals.

Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease.

BACKGROUND: Black race has been shown to be a risk factor for amputation in peripheral artery disease (PAD); however, race has been argued to be a marker for socioeconomic status (SES) rather than true disparity. The aim of this study is to study the impact of race and SES on amputation risk in PAD patients. METHODS AND RESULTS: Patients with incident PAD in the national Veterans Affairs Corporate Data Warehouse were identified from 2003 to 2014 (N=155 647). The exposures were race and SES (measured by median income in residential ZIP codes). The outcome was incident major amputation. Black veterans were significantly more likely to live in low-SES neighborhoods and to present with advanced PAD. Black patients had a higher amputation risk in each SES stratum compared with white patients. In Cox models (adjusting for covariates), black race was associated with a 37% higher amputation risk compared with white race (hazard ratio: 1.37; 95% confidence interval, 1.30-1.45), whereas low SES was independently predictive of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval, 1.06-1.17) and showed no evidence of interaction with race. In predicted amputation risk analysis, black race and low SES continued to be significant risk factors for amputation regardless of PAD presentation. CONCLUSIONS: Black race significantly increases the risk of amputation within the same SES stratum compared with white race and has an independent effect on limb loss after controlling for comorbidities, severity of PAD at presentation, and use of medications.

Lipid management in contemporary community practice: Results from the Provider Assessment of Lipid Management (PALM) Registry.

BACKGROUND: The latest cholesterol guidelines have shifted focus from achieving low-density lipoprotein cholesterol (LDL-C) targets toward statin use and intensity guided by atherosclerotic cardiovascular disease (ASCVD) risk. METHODS: Statin use and intensity were evaluated in 5,905 statin-eligible primary or secondary prevention patients from 138 PALM Registry practices. RESULTS: Overall, 74.7% of eligible adults were on statins; only 42.4% were on guideline-recommended intensity. Relative to primary prevention patients, ASCVD patients were more likely to be on a statin (83.6% vs 63.4%, P<.0001) and guideline-recommended intensity (47.3% vs 36.0%, P<.0001). Men were more likely than women to be prescribed recommended intensity for primary (odds ratio [OR] 1.87, 95% CI 1.49-2.34) and secondary (OR 1.47, 95% CI 1.26-1.70) prevention. In primary prevention, increasing age, diabetes, obesity, hypertension, and lower 10-year ASCVD risk were associated with increased odds of receiving recommended intensity. Among ASCVD patients, those with coronary artery disease were more likely to be on recommended intensity than cerebrovascular or peripheral vascular disease patients (OR 1.71, 95% CI 1.41-2.09), as were those seen by cardiologists (OR 1.43, 95% CI 1.12-1.83). Median LDL-C levels were highest among patients not on statins (124.0 mg/dL) and slightly higher among those on lower-than-recommended intensity compared with recommended-therapy recipients (88.0 and 84.0 mg/dL, respectively; P≤.0001). CONCLUSIONS: In routine contemporary practice, 1 in 4 guideline-eligible patients was not on a statin; less than half were on the recommended statin intensity. Untreated and undertreated patients had significantly higher LDL-C levels than those receiving guideline-directed statin treatment.

Increased cardiovascular disease, resource use, and costs before the clinical diagnosis of diabetes in veterans in the southeastern U.S.

IMPORTANCE: Screening for diabetes might be more widespread if adverse associations with cardiovascular disease (CVD), resource use, and costs were known to occur earlier than conventional clinical diagnosis. OBJECTIVE: The purpose of this study was to determine whether adverse effects associated with diabetes begin prior to clinical diagnosis. DESIGN: Veterans with diabetes were matched 1:2 with controls by follow-up, age, race/ethnicity, gender, and VA facility. CVD was obtained from ICD-9 codes, and resource use and costs from VA datasets. SETTING: VA facilities in SC, GA, and AL. PARTICIPANTS: Patients with and without diagnosed diabetes. MAIN OUTCOME MEASURES: Diagnosed CVD, resource use, and costs. RESULTS: In this study, the 2,062 diabetic patients and 4,124 controls were 63 years old on average, 99 % male, and 29 % black; BMI was 30.8 in diabetic patients vs. 27.8 in controls (p<0.001). CVD prevalence was higher and there were more outpatient visits in Year -4 before diagnosis through Year +4 after diagnosis among diabetic vs. control patients (all p<0.01); in Year -2, CVD prevalence was 31 % vs. 24 %, and outpatient visits were 22 vs. 19 per year, respectively. Total VA costs/year/veteran were higher in diabetic than control patients from Year -4 ($4,083 vs. $2,754) through Year +5 ($8,347 vs. $5,700) (p<0.003) for each, reflecting underlying increases in outpatient, inpatient, and pharmacy costs (p<0.05 for each). Regression analysis showed that diabetes contributed an average of $1,748/year to costs, independent of CVD (p<0.001). CONCLUSIONS AND RELEVANCE: VA costs per veteran are higher--over $1,000/year before and $2,000/year after diagnosis of diabetes--due to underlying increases in outpatient, inpatient, and pharmacy costs, greater number of outpatient visits, and increased CVD. Moreover, adverse associations with veterans' health and the VA healthcare system occur early in the natural history of the disease, several years before diabetes is diagnosed. Since adverse associations begin before diabetes is recognized, greater consideration should be given to systematic screening in order to permit earlier detection and initiation of preventive management. Keeping frequency of CVD and marginal costs in line with those of patients before diabetes is currently diagnosed has the potential to save up to $2 billion a year.

Incident heart failure in relation to vascular disease: insights from the Health, Aging, and Body Composition Study.

AIMS: The contribution of heart failure (HF) unrelated to vascular disease to the overall HF burden in older adults is not well characterized. This was investigated in this study. METHODS AND RESULTS: We assessed HF incidence and outcomes in 2895 participants of the Health ABC Study (age 74 ± 3 years, 48.4% men, 41.4% black) in relation to vascular disease (coronary, peripheral, or cerebrovascular disease) either present at baseline or developed prior to HF. During 11.4 years follow-up, 493 participants developed HF; 134 (27.2%) in participants without any prior vascular disease and 177 (36.8%) without coronary disease. Both baseline [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.9-2.8] and incident vascular disease (HR 4.3, 95% CI 3.6-5.2) were associated with HF. During a median follow-up of 2.1 years after HF onset, 67.5% participants died. Annual mortality after HF development was 21.3% in those with compared with 24.6% in those without vascular disease (HR 1.11, 95% CI 0.87-1.43; P = 0.399). There were 658 all-cause (436.3/1000 person-years) and 523 HF-related (346.4/1000 person-years) hospitalizations after HF development. There was no significant difference in hospitalizations between those with and without vascular disease [rate ratio (RR) 1.04, 95% CI 0.86-1.24 for all-cause, and RR 0.84 95% CI 0.69-1.02 for HF hospitalization]. HF with preserved EF was more common in participants without vascular disease (67.0% vs. 55.0%, P = 0.040). CONCLUSION: A significant proportion of HF in older adults develops without prior vascular disease. Outcomes for these patients are poor compared with those with preceding vascular disease. These data suggest the need for more targeted HF prediction and prevention efforts.

Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially. METHODS AND RESULTS: To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%. CONCLUSIONS: These findings indicate CVD prevalence and costs are projected to increase substantially. Effective prevention strategies are needed if we are to limit the growing burden of CVD.

Improved near-term coronary artery disease risk classification with gated stress myocardial perfusion SPECT.

OBJECTIVES: We compared analytical approaches to estimate the added value of myocardial perfusion single-photon emission computed tomography (MPS) variables in estimating coronary artery disease (CAD) outcomes. BACKGROUND: Stress MPS markers of regional ischemia are strong estimators of prognosis. Evidence published to date has not compared analytical methods to establish the added value of stress MPS and to define a clinically meaningful approach to detect improve classification of risk. METHODS: A total of 4,575 patients were consecutively and prospectively enrolled in the Myoview Prognosis Registry. Multivariable Cox proportional hazards model were employed to estimate CAD death or myocardial infarction (MI). Risk reclassification methods were also calculated. RESULTS: In risk-adjusted models (including age, sex, presenting symptoms, stress type, CAD history, and risk factors), stress MPS ischemia, rest and post-stress left ventricular ejection fraction (LVEF) (all p < 0.0001) were all significant estimators of CAD death or MI. In this multivariable model, 34% of the model chi-square was contributed by MPS ischemia. In receiver-operating characteristic curve analysis, the area under the curve increased from 0.61 to 0.66 when rest and post-stress LVEF were combined with pre-test CAD likelihood (p < 0.0001), increasing to 0.69 for MPS ischemia (p < 0.0001). The net reclassification improvement (NRI) by adding the Duke Treadmill Score (DTS) to a model including pre-test CAD likelihood was 0.112. The cost per NRI was $57 for the exercise test as compared with an office visit for risk stratification purposes. Further, the NRI by adding MPS ischemia to a model with the DTS and pre-test CAD likelihood was 0.358. The cost per NRI was $615 for the stress MPS as compared with an exercise test. CONCLUSIONS: Stress-induced ischemia is independently predictive of near-term CAD outcomes. Analytical approaches that establish the reclassification of events provide a unique approach and may serve as a quality imaging metric for estimation of improved health outcomes for stress MPS as well as for comparison to other imaging modalities.

Attained educational level and incident atherothrombotic events in low- and middle-income compared with high-income countries.

BACKGROUND: Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low- and middle-income countries (LMICs), which bear >80% of the global burden of cardiovascular disease. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs (P<0.0001), more modest in women from HICs (P=0.0026) and in men from LMICs (P=0.082), and essentially absent in women from LMICs (P=0.32). CONCLUSION: In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women.

Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: results from the Framingham Offspring Study.

BACKGROUND: We evaluated direct low density lipoprotein (LDL) cholesterol (C) and high density lipoprotein (HDL) cholesterol (C) versus standard methods using fasting plasma samples from participants in cycle 6 of the Framingham Offspring Study. METHODS: Direct LDL-C and HDL-C measurements were performed on fasting plasma from male (1335 controls, 173 CHD cases) and female (1606 controls, 74 cases) participants, and compared with LDL-C, as calculated with the Friedewald formula, and HDL-C, as measured after dextran-Mg(2+) precipitation. RESULTS: Values for direct LDL-C and HDL-C correlated well with standard methods (both about r(2)=0.94, p<0.001) with similar absolute values. Biases of >10% were present for 7.7% of samples for LDL-C, while for HDL-C this value was 8.5%. Despite higher use of cholesterol-lowering medication in CHD cases, calculated or direct LDL-C values were still well above recommended values [<2.6 mmol/L (100 mg/dL)] in CHD cases, especially in females. CONCLUSIONS: Direct assays for both LDL-C and HDL-C provide an acceptable guide for lipid treatment. In Framingham Offspring Study participants most CHD cases had LDL-C levels above the recommended target.

Predictors of incident heart failure in a large insured population: a one million person-year follow-up study.

BACKGROUND: Studies on the incidence and predictors of heart failure (HF) are often restricted to elderly persons or identify only inpatient cases. METHODS AND RESULTS: We determined the incidence and predictors of new HF diagnosed in either outpatient or inpatient settings, among 359 947 women and men (age ≥18 years) insured by Kaiser Permanente Georgia at any time during calendar years 2000 to 2005. Subjects were free of HF at baseline, and incident HF was identified with ICD-9 codes (1 inpatient or 2 outpatient HF visits). We developed multivariable Cox models to assess the association of antecedent factors (coronary heart disease, hypertension, diabetes mellitus, atrial fibrillation, and valvular heart disease) with incident HF. Separate models were created for each sex and for newly diagnosed HF in outpatient or inpatient settings. There were 4001 incident HF cases (50% women and 48% in subjects <65 years old), during 1 015 794 person-years of follow-up. The incidence rate of HF was greater in men than in women (4.24 versus 3.68 per 1000 person-years) but was stable across the study interval in both sexes. Two thirds of incident HF cases from this population occurred in outpatients. These 5 antecedent factors and age yielded excellent discrimination for incident HF in both outpatients and inpatients and in both sexes (C >0.85 in all models). CONCLUSIONS: Common modifiable risk factors accurately discriminate women and men at risk for HF diagnosed in either outpatient or inpatient settings. Approximately two thirds of new HF cases in our insured population were diagnosed in outpatients; more research is needed to characterize these subjects and their prognosis.