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Harlan M Krumholz

Publications and source records attributed to Harlan M Krumholz.

At least 19 recordsLinked to original sources
PubMed2025

Coronary Artery Disease-Based Polygenic Risk Score in Early-Onset Acute Myocardial Infarction Subtypes.

BACKGROUND: The coronary artery disease-based polygenic risk score (PRS-CAD) estimates risk of acute myocardial infarction (AMI), but its performance across AMI subtypes in younger individuals, especially women, remains uncertain. OBJECTIVES: The authors assessed PRS-CAD's performance in AMI subtypes. METHODS: We included 2,079 AMI patients aged 18 to 55 years with a 2:1 female-to-male ratio from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study and 3,761 controls from the MESA (Multi-Ethnic Study of Atherosclerosis) study. AMI subtypes were classified using the VIRGO taxonomy. We evaluated PRS-CAD's association with AMI subtypes using multinomial logistic regression and with 1-year outcomes in AMI subtypes using Cox regression. RESULTS: PRS-CAD was significantly associated with MI due to coronary artery disease (N = 1,876; OR: 1.82 per 1-SD increase; 95% CI: 1.67-1.97; P < 0.001) but not with MI with nonobstructive coronary artery disease (N = 188; OR: 1.13 per 1-SD increase; 95% CI: 0.96-1.34; P = 0.14). PRS-CAD's performance did not differ by sex. A 1-SD increase in PRS-CAD was associated with higher risk of 1-year hospitalization or death in patients with MI with nonobstructive coronary artery disease (HR: 1.50; 95% CI: 1.08-2.10; P = 0.02) but not in patients with MI due to coronary artery disease (HR: 0.98; 95% CI: 0.91-1.07; P = 0.67). CONCLUSIONS: PRS-CAD's association with AMI varied by subtype but not by sex in young adults, warranting caution in application.

acute myocardial infarction↗
PubMed2025

Targeting the SARS-CoV-2 reservoir in long COVID.

There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.

Humans↗
PubMed2007

Impact of race on the professional lives of physicians of African descent.

BACKGROUND: Increasing the racial and ethnic diversity of the physician workforce is a national priority. However, insight into the professional experiences of minority physicians is limited. This knowledge is fundamental to developing effective strategies to recruit, retain, and support a diverse physician workforce. OBJECTIVE: To characterize how physicians of African descent experience race in the workplace. DESIGN: Qualitative study based on in-person and in-depth racially concordant interviews using a standard discussion guide. SETTING: The 6 New England states in the United States. PARTICIPANTS: 25 practicing physicians of African descent representing a diverse range of primary practice settings, specialties, and ages. MEASUREMENTS: Professional experiences of physicians of African descent. RESULTS: 1) Awareness of race permeates the experience of physicians of African descent in the health care workplace; 2) race-related experiences shape interpersonal interactions and define the institutional climate; 3) responses to perceived racism at work vary along a spectrum from minimization to confrontation; 4) the health care workplace is often silent on issues of race; and 5) collective race-related experiences can result in "racial fatigue," with personal and professional consequences for physicians. LIMITATIONS: The study was restricted to New England and may not reflect the experiences of physicians in other geographic regions. The findings are meant to be hypothesis-generating and require additional follow-up studies. CONCLUSIONS: The issue of race remains a pervasive influence in the work lives of physicians of African descent. Without sufficient attention to the specific ways in which race shapes physicians' work experiences, health care organizations are unlikely to create environments that successfully foster and sustain a diverse physician workforce.

Adult↗
PubMed2006

Regional differences in process of care and outcomes for older acute myocardial infarction patients in the United States and Ontario, Canada.

BACKGROUND: Previous comparisons of acute myocardial infarction (AMI) treatment between the United States and Canada are limited because they compared selected patients from randomized trials, used administrative data that lacked clinical detail, or did not consider regional differences in AMI treatment. METHODS AND RESULTS: We compared medication use, invasive cardiac procedure use, and 30-day risk-standardized mortality rates of 38,886 fee-for-service Medicare beneficiaries hospitalized with AMI in the United States and 5634 similarly aged patients in Ontario, Canada, from 1998 and 2001. Baseline characteristics and illness severity across the US regions and Ontario were not substantially different. Cardiac catheterization use in AMI patients was significantly higher in the United States compared with Ontario (38.7% versus 16.8%, P<0.001), but significant regional variations existed, in which the northeastern United States had significantly lower utilization rates (25.6%) compared with other US regions. Beta-blocker use among ideal candidates was highest in the northeastern United States (77.6% versus 69.7% in the United States as a whole, P<0.001) and angiotensin-converting enzyme inhibitor use was highest in Ontario (69.1% versus 58.2% in the United States, P<0.001). Risk-standardized mortality rates at 30 days were not substantially different across the regions. CONCLUSIONS: Previous studies have suggested a clear divergence in invasive cardiac therapy for AMI patients between the United States and Canada on the basis of health care financing and structural differences. Our findings of similar treatment patterns in the northeastern United States and Ontario suggest that regional practices may have a greater impact on treatment patterns than the respective health care delivery systems.

Aged↗
PubMed2006

Relation between Medicare screening reimbursement and stage at diagnosis for older patients with colon cancer.

CONTEXT: Medicare's reimbursement policy was changed in 1998 to provide coverage for screening colonoscopies for patients with increased colon cancer risk, and expanded further in 2001 to cover screening colonoscopies for all individuals. OBJECTIVE: To determine whether the Medicare reimbursement policy changes were associated with an increase in either colonoscopy use or early stage colon cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Patients in the Surveillance, Epidemiology, and End Results Medicare linked database who were 67 years of age and older and had a primary diagnosis of colon cancer during 1992-2002, as well as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology, and End Results areas but who were not diagnosed with cancer. MAIN OUTCOME MEASURES: Trends in colonoscopy and sigmoidoscopy use among Medicare beneficiaries without cancer were assessed using multivariate Poisson regression. Among the patients with cancer, stage was classified as early (stage I) vs all other (stages II-IV). Time was categorized as period 1 (no screening coverage, 1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3 (universal coverage, July 2001-December 2002). A multivariate logistic regression (outcome = early stage) was used to assess temporal trends in stage at diagnosis; an interaction term between tumor site and time was included. RESULTS: Colonoscopy use increased from an average rate of 285/100,000 per quarter in period 1 to 889 and 1919/100,000 per quarter in periods 2 (P<.001) and 3 (P vs 2<.001), respectively. During the study period, 44,924 eligible patients were diagnosed with colorectal cancer. The proportion of patients diagnosed at an early stage increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in period 3 (P<.001 for each pairwise comparison). The changes in Medicare coverage were strongly associated with early stage at diagnosis for patients with proximal colon lesions (adjusted relative risk period 2 vs 1, 1.19; 95% confidence interval, 1.13-1.26; adjusted relative risk period 3 vs 2, 1.10; 95% confidence interval, 1.02-1.17) but weakly associated, if at all, for patients with distal colon lesions (adjusted relative risk period 2 vs 1, 1.07; 95% confidence interval, 1.01-1.13; adjusted relative risk period 3 vs 2, 0.97; 95% confidence interval, 0.90-1.05). CONCLUSIONS: Expansion of Medicare reimbursement to cover colon cancer screening was associated with an increased use of colonoscopy for Medicare beneficiaries, and for those who were diagnosed with colon cancer, an increased probability of being diagnosed at an early stage. The selective effect of the coverage change on proximal colon lesions suggests that increased use of whole-colon screening modalities such as colonoscopy may have played a pivotal role.

Aged↗
PubMed2006

Risks associated with statin therapy: a systematic overview of randomized clinical trials.

BACKGROUND: Although statins reduce the risk of cardiovascular events, concerns about adverse effects may deter physicians from prescribing these agents. We performed a systematic overview of randomized statin trials to quantify the risks of musculoskeletal, renal, and hepatic complications associated with therapy. METHODS AND RESULTS: Major statin trials were identified by electronic search of the MEDLINE database from 1966 to December 2005. We included English language reports of adults with documented hyperlipidemia; double-blind, random allocation of > or = 100 patients to statin monotherapy versus placebo; and reports of myalgia, creatine kinase elevations, rhabdomyolysis, transaminase elevations, and discontinuation due to adverse events. Among 74,102 subjects enrolled in 35 trials (follow-up range, 1 to 65 months), statin therapy (excluding cerivastatin) did not result in significant absolute increases in risks of myalgias (risk difference/1000 patients [RD], 2.7; 95% CI, -3.2 to 8.7), creatine kinase elevations (RD, 0.2; 95% CI, -0.6 to 0.9), rhabdomyolysis (RD, 0.4; 95% CI, -0.1 to 0.9), or discontinuation due to any adverse event (RD, -0.5; 95% CI, -4.3 to 3.3). The absolute risk of transaminase elevations was significantly higher with statin therapy (RD, 4.2; 95% CI, 1.5 to 6.9). CONCLUSIONS: On the basis of data available from published clinical trials, statin therapy is associated with a small excess risk of transaminase elevations, but not of myalgias, creatine kinase elevations, rhabdomyolysis, or withdrawal of therapy compared with placebo. Further study is necessary to determine whether the results from these published clinical trials are similar to what occurs in routine practice, particularly among patients who are older, have more severe comorbid conditions, or receive higher statin doses than most patients in these clinical trials.

Adult↗
PubMed2006

Trends in acute myocardial infarction in 4 US states between 1992 and 2001: clinical characteristics, quality of care, and outcomes.

BACKGROUND: Because of the health impact of acute myocardial infarction (AMI), substantial resources have been dedicated to improving AMI care and outcomes. Long-term trends in the clinical characteristics, quality of care, and outcomes for AMI over time from the health system perspective in geographically diverse populations are not well known. METHODS AND RESULTS: The present study included 20,550 Medicare patients aged > or = 65 years hospitalized in 4 US states (Alabama, Connecticut, Iowa, Wisconsin) with the confirmed primary discharge diagnosis of AMI in 4 periods: 1992-1993 (n=10,292), 1995 (n=5566), 1998-1999 (n=2413), and 2000-2001 (n=2279). With the use of standard quality indicator definitions, treatment of ideal candidates with aspirin and beta-blockers within 24 hours after presentation, beta-blockers, and angiotensin-converting enzyme inhibitors at discharge was assessed. Multivariable models were constructed to calculate adjusted 1-year mortality. The hospitalized Medicare population with AMI changed substantially during 1992-2001, with increasing age, more comorbidity, and fewer meeting ideal treatment criteria. Although treatment rates increased significantly for all medications, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors were not provided at discharge to 12.6%, 19.7%, and 25.2% of ideal candidates, respectively, in 2000-2001. Crude 1-year mortality increased (27.6%, 28.3%, 30.6%, and 31.0%; P=0.003 for trend, but adjusted mortality declined (compared with 1992-1993, relative risk in 1995=0.94 [95% CI, 0.88 to 1.01]; relative risk in 1998-1999=0.91 [95% CI, 0.85 to 0.98]; relative risk in 2000-2001=0.87 [95% CI, 0.81 to 0.94]). CONCLUSIONS: The quality of care and adjusted 1-year mortality improved significantly for Medicare beneficiaries with AMI during 1992-2001. Nevertheless, fewer were ideal for guideline-based therapy, and absolute mortality remains high, suggesting the need for treatment strategies applicable to a broader range of older patients.

Aged↗
PubMed2006

Strategies for reducing the door-to-balloon time in acute myocardial infarction.

BACKGROUND: Prompt reperfusion treatment is essential for patients who have myocardial infarction with ST-segment elevation. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon time) during primary percutaneous coronary intervention should be 90 minutes or less. However, few hospitals meet this objective. We sought to identify hospital strategies that were significantly associated with a faster door-to-balloon time. METHODS: We surveyed 365 hospitals to determine whether each of 28 specific strategies was in use. We used hierarchical generalized linear models and data on patients from the Centers for Medicare and Medicaid Services to determine the association between hospital strategies and the door-to-balloon time. RESULTS: In multivariate analysis, six strategies were significantly associated with a faster door-to-balloon time. These strategies included having emergency medicine physicians activate the catheterization laboratory (mean reduction in door-to-balloon time, 8.2 minutes), having a single call to a central page operator activate the laboratory (13.8 minutes), having the emergency department activate the catheterization laboratory while the patient is en route to the hospital (15.4 minutes), expecting staff to arrive in the catheterization laboratory within 20 minutes after being paged (vs. >30 minutes) (19.3 minutes), having an attending cardiologist always on site (14.6 minutes), and having staff in the emergency department and the catheterization laboratory use real-time data feedback (8.6 minutes). Despite the effectiveness of these strategies, only a minority of hospitals surveyed were using them. CONCLUSIONS: Several specific hospital strategies are associated with a significant reduction in the door-to-balloon time in the management of myocardial infarction with ST-segment elevation.

Angioplasty, Balloon, Coronary↗
PubMed2006

The effect of age and chronic illness on life expectancy after a diagnosis of colorectal cancer: implications for screening.

BACKGROUND: Older adults with shorter life expectancies may receive less benefit from colorectal cancer screening than younger, healthier patients. OBJECTIVE: To determine the degree to which life expectancy after diagnosis of an early-stage cancer varies according to age or coexisting chronic illness. DESIGN: Retrospective cohort study. SETTING: Population-based cancer registry with linked administrative claims data. PATIENTS: Patients 67 years of age or older who received a diagnosis of colorectal cancer from 1993 through 1999. MEASUREMENTS: Chronic conditions were identified by searching Medicare claims. Using a life-table approach, the authors quantified the degree to which life expectancy associated with each cancer stage at diagnosis varied with patient age, sex, and burden of chronic conditions. RESULTS: The final study sample consisted of 35 755 patients. After accounting for cancer stage at diagnosis, the authors found that life expectancy was strongly related to both age and the burden of chronic illness. Among men who received a diagnosis of stage I cancer at 67 years of age, life expectancy decreased from 19.1 years (95% CI, 17.8 to 20.5 years) for patients with no chronic conditions to 12.4 years (CI, 11.4 to 13.5 years) for those with 1 or 2 conditions and 7.6 years (CI, 6.1 to 9.4 years) for those with 3 or more conditions. A similar trend was noted among female counterparts, with life expectancy decreasing from approximately 23 years to 16 years and 7 years for the 3 chronic condition groups, respectively. For men and women 81 years of age with no chronic illnesses, life expectancy after stage I cancer diagnosis was 10.3 years (CI, 9.2 to 11.9 years) and 13.8 years (CI, 12.3 to 15.3 years), respectively. LIMITATIONS: Administrative claims may not identify all chronic conditions. Life expectancy estimates at the population level are averages and, therefore, may not accurately predict the life expectancy of individual patients. CONCLUSIONS: Coexisting chronic illness is associated with a substantial reduction in life expectancy after diagnosis of early-stage colorectal cancer. Physicians should consider this when deciding whether to screen older persons.

Age Factors↗
PubMed2006

Achieving quality in cardiovascular imaging: proceedings from the American College of Cardiology-Duke University Medical Center Think Tank on Quality in Cardiovascular Imaging.

Cardiovascular imaging has enjoyed both rapid technological advances and sustained growth, yet less attention has been focused on quality than in other areas of cardiovascular medicine. To address this deficit, representatives from cardiovascular imaging societies, private payers, government agencies, the medical imaging industry, and experts in quality measurement met, and this report provides an overview of the discussions. A consensus definition of quality in imaging and a convergence of opinion on quality measures across imaging modalities was achieved and are intended to be the start of a process culminating in the development, dissemination, and adoption of quality measures for all cardiovascular imaging modalities.

Academic Medical Centers↗
PubMed2006

Impact of chronic kidney disease on health-related quality-of-life improvement after coronary artery bypass surgery.

BACKGROUND: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG). METHODS: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5). RESULTS: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores. CONCLUSIONS: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Activities of Daily Living↗
PubMed2006

Time course of depression and outcome of myocardial infarction.

BACKGROUND: Depression predicts worse outcomes after myocardial infarction (MI), but whether its time course in the month following MI has prognostic importance is unknown. Our objective was to evaluate the prognostic importance of transient, new, or persistent depression on outcomes at 6 months after MI. METHODS: In a prospective registry of acute MI (Prospective Registry Evaluating outcomes after Myocardial Infarction: Events and Recovery [PREMIER]), depressive symptoms were measured in 1873 patients with the Patient Health Questionnaire (PHQ) during hospitalization and 1 month after discharge and were classified as transient (only at baseline), new (only at 1 month), or persistent (at both times). Outcomes at 6 months included (1) all-cause rehospitalization or mortality and (2) health status (angina, physical limitation, and quality of life using the Seattle Angina Questionnaire). RESULTS: Compared with nondepressed patients, all categories of depression were associated with higher rehospitalization or mortality rates, more frequent angina, more physical limitations, and worse quality of life. The adjusted hazard ratios for rehospitalization or mortality were 1.34, 1.71, and 1.42 for transient, new, and persistent depression, respectively (all P<.05). Corresponding odds ratios were 1.62, 2.73, and 2.64 (all P<.01) for angina and 1.69, 2.25, and 3.27 (all P<.05) for physical limitation. Depressive symptoms showed a stronger association with health status compared with traditional measures of disease severity. CONCLUSION: Depressive symptoms after MI, irrespective of whether they persist, subside, or newly develop in the first month after hospitalization, are associated with worse outcomes after MI.

Activities of Daily Living↗
PubMed2006

Health related quality of life after mitral valve repairs and replacements.

BACKGROUND: The decision to replace or repair mitral valves is often a difficult decision, and outcomes from the patients' perspective should guide decision-making. We investigated whether the change in health related quality of life (HRQOL) after mitral valve surgery is different after valve repairs compared with replacements. METHODS: We prospectively studied 25 patients with mitral valve replacement and 45 patients with valve repairs performed in 1998-99. We measured HRQOL at baseline and at 18 months using the Medical Outcomes Trust Short Form 36-item Health Survey (SF-36) questionnaire. We compared mean HRQOL scores of the groups with age-adjusted U.S. population scores. We used analysis of covariance to determine a change in HRQOL within groups (repair or replacement) and if the change in HRQOL was different between the groups. RESULTS: We found few differences between the groups, with more men and simultaneous coronary artery bypass graft surgery in the valve repair group and more prior operation in the valve replacement group. HRQOL improved after surgery in most domains, and was comparable to age-adjusted U.S. norms in the valve repair group. In the multivariable analysis, mitral valve repair recipients reported higher social functioning compared with patients who received valve replacement (p = 0.04). We did not find other statistically significant differences. However, the adjusted improvements in the component scales of physical functioning (PCS) and mental functioning (MCS) were substantial in the valve repair group (mean changes: PCS = 6.8, p = 0.003; MCS = 8.1, p = 0.014) and less pronounced in the replacement group (mean changes: PCS = 3.6, p = 0.09; MCS = 4.3, fsp = 0.16). CONCLUSIONS: While many considerations influence the decision to repair or replace mitral valves, these findings suggest that repair may be better from the health status perspective. Further studies are necessary to validate this finding.

Aged↗
PubMed2006

Impact of medication therapy discontinuation on mortality after myocardial infarction.

BACKGROUND: Nonadherence to medications is common, but the determinants and consequences are poorly defined. The objectives of this study were to identify patient and myocardial infarction (MI) treatment factors associated with medication therapy discontinuation and to assess the impact of medication discontinuation 1 month after MI on 12-month mortality. METHODS: This was a multicenter prospective cohort of patients with MI enrolled in the Prospective Registry Evaluating Myocardial Infarction: Event and Recovery study. The outcomes were use of aspirin, beta-blockers, and statins at 1 month after MI hospitalization among patients discharged with all 3 medications as well as 12-month mortality. RESULTS: Of 1521 patients discharged with all 3 medications, 184 discontinued use of all 3 medications, 56 discontinued use of 2 medications, 272 discontinued use of 1 medication, and 1009 continued taking all 3 medications at 1 month. In multivariable analyses, patients not graduating from high school (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.20-2.60) were more likely to discontinue use of all medications. The effect of increasing age on medication therapy discontinuation was greater for females (OR, 1.77; 95% CI, 1.34-2.34) than males (OR, 1.23; 95% CI, 1.02-1.47). Patients who discontinued use of all medications at 1 month had lower 1-year survival (88.5% vs 97.7%; log-rank P<.001) compared with patients who continued to take 1 or more medication(s). In multivariable survival analysis, medication therapy discontinuation was independently associated with higher mortality (hazards ratio, 3.81; 95% CI, 1.88-7.72). Results were consistent when evaluating discontinuation of use of aspirin, beta-blockers, and statins separately. CONCLUSIONS: Medication therapy discontinuation after MI is common and occurs early after discharge. Patients who discontinue taking evidence-based medications are at increased mortality risk. These findings suggest the need to improve the transition of care from the hospital to outpatient setting to ensure that patients continue to take medications that have mortality benefit.

Adrenergic beta-Antagonists↗