Changing Drivers of Mortality Among Patients Referred for Cardiac Stress Testing.
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ABSTRACT: Objective
To identify temporal shifts in coronary artery disease (CAD) risk factor profiles, clinical parameters, and corresponding mortality rates among patients referred for radionuclide stress testing over 22 years.Patients and methods
We assessed 39,750 patients with suspected CAD ("diagnostic" patients) and 10,982 patients with known CAD who underwent radionuclide stress testing between January 2, 1991, and December 31, 2012, and were followed up for at least 5 years (median, 12.7 years).Results
Among both diagnostic patients and those with known CAD, there was a marked temporal decline in typical angina and myocardial ischemia. However, several risk factors for disease progressively increased, including diabetes, obesity, and hypertension. In addition, the need to perform pharmacological testing in lieu of exercise increased markedly between the first and fourth epochs among both diagnostic patients (from 26.5% [1634 of 6176] to 53.0% [5781 of 10,908]; P<.001) and patients with known CAD (from 31.1% [999 of 3213] to 75.5% [1405 of 1860]; P<.001). The net effect of these competing positive and negative risk factor trends was no change in the adjusted annualized rate of mortality over the temporal span in our study, ranging from 1.57% per year in 1991-1995 to 1.76% per year in 2006-2012 among diagnostic patients and from 2.46% per year to 2.75% per year during the same intervals among patients with known CAD.Conclusion
Our findings suggest a marked contemporary shift in the drivers of all-cause mortality among patients undergoing cardiac stress tests away from such factors as typical angina and inducible myocardial ischemia, which are declining in prevalence, and toward such factors as diabetes and an inability to perform exercise, which are increasing in prevalence.
SUBMITTER: Rozanski A
PROVIDER: S-EPMC8240348 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDiabetes mellitus (DM) is increasingly prevalent among contemporary populations referred for cardiac stress testing, but its potency as a predictor for major adverse cardiovascular events (MACE) vs other clinical variables is not well delineated.Methods and resultsFrom 19,658 patients who underwent SPECT-MPI, we identified 3122 patients with DM without known coronary artery disease (CAD) (DM+/CAD-) and 3564 without DM with known CAD (DM-/CAD+). Propensity score matching was used to control for the differences in characteristics between DM+/CAD- and DM-/CAD+ groups. There was comparable MACE in the matched DM+/CAD- and DM-/CAD+ groups (HR 1.15, 95% CI 0.97-1.37). By Chi-square analysis, type of stress (exercise or pharmacologic), total perfusion deficit (TPD), and left ventricular function were the most potent predictors of MACE, followed by CAD and DM status. The combined consideration of mode of stress, TPD, and DM provided synergistic stratification, an 8.87-fold (HR 8.87, 95% CI 7.27-10.82) increase in MACE among pharmacologically stressed patients with DM and TPD > 10% (vs non-ischemic, exercised stressed patients without DM).ConclusionsPropensity-matched patients with DM and no known CAD have similar MACE risk compared to patients with known CAD and no DM. DM is synergistic with mode of stress testing and TPD in predicting the risk of cardiac stress test patients.
| S-EPMC9085969 | biostudies-literature
Project description:BackgroundHome Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown.ObjectivesTo compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR).MethodsWe performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status.ResultsA total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05).ConclusionCompletion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.
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Project description:Cardiovascular risk stratification is often performed in patients considered for renal transplantation. In a single center, we sought to examine the association between abnormal stress testing with imaging and post-renal transplant major adverse cardiovascular events (MACE) using multivariable logistic regression. From January 2006 to May 2016 232 patients underwent renal transplantation and 59 (25%) had an abnormal stress test result. Compared to patients with a normal stress test, patients with an abnormal stress test had a higher prevalence of dyslipidemia, diabetes mellitus, obesity, coronary artery disease (CAD), and heart failure. Among those with an abnormal result, 45 (76%) had mild, 10 (17%) moderate, and 4 (7%) severe ischemia. In our cohort, 9 patients (3.9%) had MACE at 30-days post-transplant, 5 of whom had an abnormal stress test. The long-term MACE rate, at a median of 5 years, was 32%. After adjustment, diabetes (OR 2.37, 95% CI 1.12-5.00, p = 0.02), CAD (OR: 3.05, 95% CI 1.30-7.14, p = 0.01) and atrial fibrillation (OR: 5.86, 95% CI 1.86-18.44, p = 0.002) were independently associated with long-term MACE, but an abnormal stress test was not (OR: 0.83, 95% CI 0.37-1.92, p = 0.68). In conclusion, cardiac stress testing was not an independent predictor of long-term MACE among patients undergoing renal transplant.
| S-EPMC8638939 | biostudies-literature
Project description:Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. We identified pathogenic or likely pathogenic variants in 10 index patients, all of which had short telomeres compared to age-matched healthy controls. Six of the 10 variants were novel; three in TERC (n.69_74dupAGGCGC, n.122_125delGCGG, and n.407_408delinsAA) and three in TERT (p.(D684G), p.(R774*), and p.(*1133Wext*39)). The high proportion of novel variants identified in our study highlights the need for solid interpretation of new variants that may be detected. Measurement of telomere length is a useful approach for evaluating pathogenicity of genetic variants associated with telomere-related disorders.
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Project description:Study objectivesThe multiple sleep latency test (MSLT) has limitations when evaluating disorders of hypersomnolence with unknown etiology. Alternative measures of hypersomnolence may objectively identify pathology in patients with complaints of daytime sleepiness that may not be captured by the MSLT alone. This study evaluated the impact of a multimodal hypersomnolence assessment relative to MSLT in patients with unexplained hypersomnolence.MethodsSeventy-five patients with unexplained hypersomnolence were included in the analyzed sample. Polysomnography was performed without prescribed wake time, and the psychomotor vigilance task and pupillographic sleepiness test were completed between MSLT nap opportunities. Presence or absence of hypersomnolence for each assessment was defined using a priori cutpoints. Proportions of patients identified as hypersomnolent using the multimodal assessment relative to MSLT alone were evaluated, as well as the sensitivity and specificity of ancillary hypersomnolence measures relative to MSLT as a gold standard.ResultsThe multimodal assessment more than doubled the proportion of patients identified as having objective deficits relative to MSLT ≤ 8 minutes alone. The combination of excessive sleep duration, lapses on the psychomotor vigilance task, and impairments on the pupillographic sleepiness test also had perfect sensitivity in identifying all patients identified as sleepy by the MSLT across 3 different MSLT cutpoints (5, 8, and 10 minutes).ConclusionsThese data demonstrate the insufficiency of the MSLT as a singular tool to identify objective pathology in persons with unexplained hypersomnolence. Further efforts to refine and standardize multimodal assessments will likely improve diagnostic acumen and research into the causes of these disorders.
| S-EPMC7446098 | biostudies-literature
Project description:AimsCardiac fibrosis is associated with left ventricular (LV) remodelling and contractile dysfunction in aortic stenosis (AS). The fibrotic process in this condition is still unclear. The aim of this study was to determine the role of both local and systemic inflammation as underlying mechanisms of LV fibrosis and contractile dysfunction. The diagnostic values of 2D-strain echocardiography and serum biomarkers in the evaluation of cardiac fibrosis in this condition were assessed through correlation analyses.Methods and resultsPatients with AS referred for surgical valve replacement were prospectively and consecutively included. They all had a comprehensive echocardiography including 2D strain. Blood samples were collected to measure cytokines and inflammatory biomarkers using Luminex bead-based assays. A per-surgical myocardial biopsy of the basal antero-septal segment (S1) was performed. Serial sections of each biopsy were stained with Sirius red. Digital image analysis was used to quantify fibrosis. Immunostainings using specific antibodies against macrophage, glycoprotein (gp) 130, and interleukin 6 (IL-6) were also performed. Patients were divided into tertiles reflecting the severity of fibrosis: mild, moderate, and severe load (TF1 to TF3). The mean age of the 58 included patients was 73 ± 11 years. Twenty-four (43%) were in New York Heart Association III-IV. Mean aortic valve area was 0.8 ± 0.2 cm2 . Mean aortic stenosis peak velocity and mean gradient were respectively 4.5 ± 0.8 m/s and 54 ± 15 mmHg. The mean LV ejection fraction was 54 ± 12%, and the global LV longitudinal strain was -15 ± 4%. The mean S1 strain, corresponding to the biopsied region, was -10 ± 6% and was strongly correlated to fibrosis load (R = 0.83, P < 0.0001). TF3 was associated with higher mortality (P = 0.009), higher serum C-reactive protein and IL-6, and lower gp130 compared with the other tertiles (P < 0.05). IL-6 and gp130 were expressed in the heart and respectively in the plasma membrane of macrophages and in the cytoplasm of both macrophages and cardiomyocytes. During follow-up, three patients died and were all in the third fibrosis tertile.ConclusionsWe found a positive correlation between elevated inflammatory markers and degree of fibrosis load. These two parameters were associated with worse outcomes in patients with severe AS. Our results may be of interest especially in patients for whom a transcatheter aortic valve implantation is indicated and myocardial biopsy is not possible. Strategies aiming at preventing inflammation might be considered to decrease or limit the progression of cardiac fibrosis in patients followed for AS.
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Project description:RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies.The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies.Twenty-four patients had pathogenic variants on the RASopathy panel, for a diagnostic yield of 19%. Reported features of pulmonic stenosis and ptosis were significantly correlated with a positive test result; no reported features were significantly correlated with a negative test result. We identified 27 different alternative diagnoses for patients originally suspected of having RASopathies.This study provides information that can assist in guiding differential diagnosis and genetic testing for patients suspected of having a RASopathy disorder.Genet Med advance online publication 20 October 2016.
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Project description:BackgroundDespite guidelines recommending genetic counseling for patients with early-onset renal cell carcinoma (RCC), studies interrogating the spectrum of germline mutations and clinical associations in patients with early-onset RCC are lacking.ObjectiveTo define the germline genetic spectrum and clinical associations for patients with early-onset RCC diagnosed at age ≤46 yr who underwent genetic testing.Design, setting, and participantsWe retrospectively identified patients with early-onset RCC who underwent germline testing at our institution from February 2003 to June 2020.Outcome measurement and statistical analysisThe frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined. Clinical characteristics associated with mutation status were analyzed using two-sample comparison (Fisher's exact or χ2 test).Results and limitationsOf 232 patients with early-onset RCC, 50% had non-clear-cell histology, including unclassified RCC (12.1%), chromophobe RCC (9.7%), FH-deficient RCC (7.0%), papillary RCC (6.6%), and translocation-associated RCC (4.3%). Overall, 43.5% had metastatic disease. Germline P/LP variants were identified in 41 patients (17.7%), of which 21 (9.1%) were in an RCC-associated gene and 20 (8.6%) in a non-RCC-associated gene, including 17 (7.3%) in DNA damage repair genes such as BRCA1/2, ATM, and CHEK2. Factors associated with RCC P/LP variants include bilateral/multifocal renal tumors, non-clear-cell histology, and additional extrarenal primary malignancies. In patients with only a solitary clear-cell RCC, the prevalence of P/LP variants in RCC-associated and non-RCC-associated genes was 0% and 9.9%, respectively.ConclusionsPatients with early-onset RCC had high frequencies of germline P/LP variants in genes associated with both hereditary RCC and other cancer predispositions. Germline RCC panel testing has the highest yield when patients have clinical phenotypes suggestive of underlying RCC gene mutations. Patients with early-onset RCC should undergo comprehensive assessment of personal and family history to guide appropriate genetic testing.Patient summaryIn this study of 232 patients with early-onset kidney cancer who underwent genetic testing, we found a high prevalence of mutations in genes that increase the risk of cancer in both kidneys and other organs for patients and their at-risk family members. Our study suggests that patients with early-onset kidney cancer should undergo comprehensive genetic risk assessment.
| S-EPMC8688197 | biostudies-literature
Project description:BackgroundEvaluation of angina symptoms in primary care often includes clinical exercise testing. We sought to identify clinical characteristics that predicted the outcome of exercise testing and to describe the occurrence of cardiovascular events during follow-up.MethodsThis study followed patients referred to exercise testing for suspected coronary disease by general practitioners in the County of Jämtland, Sweden (enrolment, 25 months from February 2010). Patient characteristics were registered by pre-test questionnaire. Exercise tests were performed with a bicycle ergometer, a 12-lead electrocardiogram, and validated scales for scoring angina symptoms. Exercise tests were classified as positive (ST-segment depression >1 mm and chest pain indicative of angina), non-conclusive (ST depression or chest pain), or negative. Odds ratios (ORs) for exercise-test outcome were calculated with a bivariate logistic model adjusted for age, sex, systolic blood pressure, and previous cardiovascular events. Cardiovascular events (unstable angina, myocardial infarctions, decisions on revascularization, cardiovascular death, and recurrent angina in primary care) were recorded within six months. A probability cut-off of 10% was used to detect cardiovascular events in relation to the predicted test outcome.ResultsWe enrolled 865 patients (mean age 63.5 years, 50.6% men); 6.4% of patients had a positive test, 75.5% were negative, 16.4% were non-conclusive, and 1.7% were not assessable. Positive or non-conclusive test results were predicted by exertional chest pain (OR 2.46, 95% confidence interval (CI) 1.69-3.59), a pathologic ST-T segment on resting electrocardiogram (OR 2.29, 95% CI 1.44-3.63), angina according to the patient (OR 1.70, 95% CI 1.13-2.55), and medication for dyslipidaemia (OR 1.51, 95% CI 1.02-2.23). During follow-up, cardiovascular events occurred in 8% of all patients and 4% were referred to revascularization. Cardiovascular events occurred in 52.7%, 18.3%, and 2% of patients with positive, non-conclusive, or negative tests, respectively. The model predicted 67/69 patients with a cardiovascular event.ConclusionsClinical characteristics can be used to predict exercise test outcome. Primary care patients with a negative exercise test have a very low risk of cardiovascular events, within six months. A predictive model based on clinical characteristics can be used to refine the identification of low-risk patients.
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Project description:To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000-2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.
| S-EPMC9016061 | biostudies-literature