Research Paper Cvd


Our society is aging. The number of Americans older than 65 years of age is expected to increase from 13% in 2000 to 20% by 2030 as the baby boomers enter their senior years.1 By 2050, the number above the age of 85 years is expected to triple. The practice of cardiology has become entwined with geriatric medicine.

Yet, despite these trends, our understanding of cardiovascular disease in older persons is still in many cases rudimentary. This may not be surprising, as the elderly are poorly represented in clinical research. Historically, patients older than the age of 65 years were often excluded from clinical trials. Those over the age of 85 years are still rarely included. In addition, patients with common comorbidities found in older persons such as chronic kidney disease, anemia, chronic obstructive pulmonary disease, and cognitive impairment are often intentionally kept out of clinical investigations.

Moreover, models of care are rarely optimized for older persons.2 Too often, care for vulnerable elders is procedure-based and fragmented rather than integrated and continuous with involvement of both patients and caregivers. Comorbidities, geriatric syndromes, and polypharmacy are often ignored when making treatment decisions. Quality of life, symptom palliation, and other patient-centered outcomes are often deemphasized in favor of surrogate markers and targets that are easier to measure but may not accurately reflect underlying patient risk or goals of care.

It is for these reasons that we are dedicating the topic summaries within this issue of Circulation: Cardiovascular Quality and Outcomes to cardiovascular disease in older persons. We have included studies relating cardiovascular risk to clinical syndromes often found in older persons such as frailty and heart failure with preserved ejection fraction. We have also included research on important nonpharmacologic interventions in the elderly such as exercise as well as commonly performed invasive procedures such as implantable cardioverter-defibrillator placement, percutaneous coronary intervention, and, increasingly, transcatheter aortic valve replacement. Last, we have incorporated studies that examine hospital and health system performance for older persons with heart failure, acute myocardial infarction, and stroke.

We hope you find these reviews useful, and we welcome your feedback as we try to best meet the needs of our readership.

Age-Related Differences in Characteristics, Performance Measures, Treatment Trends, and Outcomes in Patients With Ischemic Stroke


Prior studies have demonstrated lower use of guideline-recommended therapy and worse poststroke outcomes in older patients. The aim of this study was to evaluate temporal changes in adherence to performance measures and early clinical outcomes among acute ischemic stroke patients in the Get With The Guidelines (GWTG) program. The authors identified 502 036 ischemic stroke admissions among 1256 hospitals from 2003 to 2009. Data were analyzed by the following age groups: <50, 50 to 59, 60 to 69, 70 to 79, 80 to 89, and ≥90 years. Seven predefined performance measures relating to intravenous tissue plasminogen activator, antithrombotic medication, deep venous thrombosis prophylaxis, and other areas were analyzed. Mean age of ischemic stroke patients was 71 years; 52.5% were women. Although older patients (≥90 years) were less likely to be discharged home (42.1%) and more likely to die in the hospital (10.3%) compared with younger patients (<50 years), there were substantial temporal improvements in performance measures from 2003 to 2009 for each age group, and many age-related treatment gaps were narrowed or eliminated over time.


Study results are encouraging because they demonstrate significant improvement in the standard of care for acute ischemic stroke patients across the United States. Improvements in performance metrics were more frequently observed in older patients and resulted in narrowing of age-related treatment gaps. However, most of the hospitals participating in the GWTG-Stroke program are self-selected and probably have more interest in quality improvement, thereby challenging the generalizability of the results to the entire nation.3

Exercise Capacity and Mortality in Older Men: A 20-Year Follow-Up Study


Regular exercise is associated with improved life quality and survival in young and middle-aged subjects. Much less is known, however, about the effects of exercise in the elderly. The authors examined the association between physical fitness and mortality rates among 5314 elderly male veterans aged 65 to 92 years. Physical fitness categories were established on the basis of peak metabolic equivalents (METs), estimated from symptom-limited exercise tolerance testing. Over a median follow-up time of 8.1 years, 2137 patients died. Baseline exercise capacity was higher among survivors (6.3±2.4 METs versus 5.3±2.0 METs, P<0.001). Exercise capacity was a strong predictor of mortality, with ≈13% lower risk for each 1-MET increase in exercise capacity. The results were stable after adjustment for a host of variables including age, body mass index, cardiovascular risk factors, and cardiovascular medications.


This study demonstrates that higher exercise capacity predicts lower all-cause mortality among the elderly. The findings remained consistent after multivariable adjustment and a variety of sensitivity analyses. Nevertheless, as the authors expressed, it is not known to what extent exercise capacity reflects physical activity patterns. In addition, it remains unclear whether the link between exercise capacity and outcomes is causal, especially as interventions aimed at improving exercise capacity4 have not regularly conferred the anticipated magnitude of benefits seen in large observational databases such as this.5

Cystatin C and Sudden Cardiac Death Risk in the Elderly


Sudden cardiac death (SCD) has been associated with moderate kidney dysfunction in patients with cardiovascular disease. The authors sought to determine whether SCD incidence was independently associated with measurement of impaired kidney function, using standard creatinine-based estimated glomerular filtration rate (eGFR) or levels of cystatin C. Serum levels of cystatin C and creatinine were evaluated from 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. The association between cystatin C tertiles and SCD was determined, using a multivariate Cox proportional hazards model. The authors also defined 3 groups of patients using both cystatin C–based and creatinine-based eGFR measurements: normal kidney function, preclinical kidney disease, and chronic kidney disease. Over the median follow-up period of 11.2 years, 91 SCD events were reported. The annual incidence of SCD events increased across cystatin C tertiles: 10, 25, and 32 events per 10 000 person-years in tertiles 1, 2, and 3, respectively. These associations persisted after multivariate adjustment. In comparison, the rate of SCD increased in a linear distribution across creatinine-based eGFR tertiles: 15, 22, and 27 events per 10 000 person-years in tertiles 1, 2, and 3, respectively. However, after multivariate adjustment, no significant associations remained between creatinine-based eGFR and SCD. After excluding persons with chronic kidney disease, participants with preclinical kidney disease had a 2-fold SCD risk compared with those without chronic kidney disease.


The results show an association between impaired kidney function, as measured by cystatin C, and the risk of SCD that is independent of patient demographics, traditional cardiovascular risk factors, and use of common cardiac medications among ambulatory elderly in the community without clinical cardiovascular disease at baseline. While an association between chronic kidney disease and SCD has been described in the literature, this study extends the risk of SCD to the setting of preclinical kidney disease, as many persons with elevated cystatin C levels had normal serum creatinine. This study adds to the literature showing the relative superiority of cystatin C compared with creatinine as a marker of risk.6–8

National Patterns of Risk-Standardized Mortality and Readmission for Acute Myocardial Infarction and Heart Failure: Update on Publicly Reported Outcomes Measures Based on the 2010 Release


The Centers for Medicare and Medicaid Services (CMS) publicly report hospital 30-day risk-standardized mortality rates (RSMRs) and risk-standardized readmission rates (RSRRs) for patients hospitalized with acute myocardial infarction (AMI) and heart failure (HF). RSMRs and RSRRs are calculated using hierarchical logistic modeling to account for patient clustering by hospital and are risk-standardized for age, sex, and comorbidities. The authors provided a national perspective on hospital performance for the 2010 release of these measures. Between July 1, 2006, and June 30, 2009, median RSMR for AMI was 16% (range, 10.3% to 24.6%; absolute difference, 5.2% for hospitals between the 5th and 95th percentiles) and median RSMR for HF was 10.8% (range, 6.6% to 18.2%; absolute difference of 5.0% between the 5th and 95th percentiles). Median RSRR for AMI was 19.9% (range, 15.3% to 26.3%; absolute difference, 3.9% between the 5th and 95th percentiles) and median RSRR for HF was 24.5% (range, 17.3% to 32.4%; absolute difference, 6.7% between the 5th and 95th percentiles). Compared with the previous reporting period, a small percentage of hospitals had either significantly improved or worsened RSMRs or RSRRs for HF, AMI, or both conditions.


Clinically meaningful variation exists for both RSMRs and RSRRs for HF and AMI. This variation suggests that many adverse events could be averted if performance moved toward what is being achieved by the top performing institutions in the United States. As some hospitals demonstrated substantial reductions in RSMRs or RSRRs as compared with the previous reporting period, significant improvement in hospital performance is possible.9

Incidence and Prevalence of Atrial Fibrillation and Associated Mortality Among Medicare Beneficiaries, 1993 to 2007


Atrial fibrillation (AF) is a common problem among older persons and is associated with considerable morbidity and mortality. In this study, the authors measured annual incidence and prevalence of AF and mortality after an AF diagnosis in 433 123 Medicare beneficiaries aged 65 years and older who were diagnosed with AF between 1993 and 2007. The incidence of AF remained steady during the 14-year study period, ranging from 27.3 to 28.3 per 1000 person-years. Higher incidence rates were found among men and white beneficiaries. The prevalence of AF increased in all age groups throughout the entire study period (mean, 5% per year). Mortality after AF diagnosis declined slightly over time but remained high. In 2007, the age- and sex-adjusted mortality rates were 11% at 30 days and 25% at 1 year.


Older patients with AF are at surprisingly high risk for mortality within 1 year of diagnosis, with approximately one-quarter dying within this time period. As previous research has demonstrated, the major source of morbidity and mortality among patients with AF is the combination of other cardiovascular conditions besides AF as well as noncardiovascular comorbidities.10 Older patients with AF may therefore benefit from significant attention not only to their AF but also to other commonly associated cardiovascular and noncardiovascular conditions that drive a significant percentage of adverse outcomes in this population.11

Linking the National Cardiovascular Data Registry CathPCI Registry With Medicare Claims Data: Validation of a Longitudinal Cohort of Elderly Patients Undergoing Cardiac Catheterization


This study assessed the degree to which the cohort derived by linking the National Cardiovascular Data Registry's (NCDR) CathPCI Registry with the longitudinal Centers for Medicare and Medicaid (CMS) claims database, using indirect patient identifiers is representative of the overall CathPCI and CMS percutaneous coronary intervention (PCI) populations. From 2004 to 2006, 1492 hospitals filed CMS PCI claims and 663 hospitals contributed to CathPCI. Of these hospitals, 643 (97%) were linked across both data sources. Compared with all CMS PCI hospitals, the linked data set contained fewer governmental, northeastern, southern, and low-volume (<200 beds) sites. Of the 993 351 CMS beneficiaries receiving PCI, 398 508 (40.1%) were found at centers in the linked database. Of these patients, 341 916 (86%) were linked to CathPCI Registry records. Linked and unlinked CMS patients had similar demographic and clinical features. In CathPCI, 477 456 elderly patients underwent PCI; 359 077 (75%) were able to be linked to CMS claims. Linked and unlinked CathPCI patients were mostly similar with the exception of fewer patients having commercial or health maintenance organization insurance in the linked cohort.


This Methods paper provides a description of a database that will be well positioned to study cardiovascular disease in the elderly. Using deterministic matching, the authors were able to build a dataset that was representative of the elderly population undergoing PCI. This linked dataset is valuable because it leverages the extensive patient-level clinical information from CathPCI and the capacity for long-term follow-up with CMS data. This linkage should allow investigators to conduct comparative effectiveness studies that were previously not possible.12

Frail Patients Are at Increased Risk for Mortality and Prolonged Institutional Care After Cardiac Surgery


As the number of older frail patients undergoing cardiac surgery increases, the authors sought to determine if frailty was a risk factor for postprocedural adverse outcomes. The authors identified 3826 patients at a single center undergoing cardiac surgery and prospectively collected information on patients' activities of daily living (Katz index), ambulation status (completely independent versus requiring assistive device), and history of physician-documented dementia; 4.1% of patients had abnormalities in at least 1 of these 3 categories and were considered to be frail. Frail patients were older, had greater comorbidity burden, were more likely to present with acute disease, and were more likely to require more complex operative procedures. By logistic regression, frailty was an independent predictor of in-hospital mortality (odds ratio, 1.8), reduced survival at 2 years (odds ratio, 1.5), and discharge to an institution (odds ratio, 6.3).


As a concept, frailty has been defined in multiple ways. Here, frailty seems to be described primarily in terms of disability, meaning difficulty with carrying out functional tasks (activity of daily living impairment, difficulty with ambulation). Nonetheless, this characterization of preoperative frailty produced similar results with previous data showing increased hospitalization, mortality, and institutionalization among frail community-dwelling populations where frailty was defined in an alternate manner.14 Perhaps the most striking result from this study was that frail operative patients had a 6 times higher odds of being discharged to a nursing facility. Both patients and providers should be aware of this information before proceeding with surgery, as the requirement for institutionalization may in some cases be permanent.16

Frailty Is Independently Associated With Short-Term Outcomes for Elderly Patients With Non–ST-Segment Elevation–Myocardial Infarction


The authors prospectively examined the influence of frailty on 1-month outcomes after non–ST-elevation–myocardial infarction (NSTEMI). Patients were 75 years or older from 1 of 3 Swedish hospitals. Frailty was defined using the Canadian Study of Health and Aging Clinical Frailty Scale, which groups patients into 1 of 7 categories of increasing dependence on others due to comorbidity, disability, or cognitive impairment.17 This frailty scale does not require physical performance measures, only clinical judgment. Of 307 patients, 49% were considered frail (score, 5–7). Using logistic regression, frailty was independently associated with the primary composite outcome (death, reinfarction, revascularization due to ischemia, hospitalization, major bleeding, stroke/transient ischemic attack, need for dialysis up to 1 month after inclusion) (odds ratio, 2.2), in-hospital mortality (odds ratio, 4.7), and 1-month mortality (odds ratio, 4.7). Frail patients were less likely to undergo cardiac catheterization or intensive care unit admission.


The traditional assessment of frailty using hand-grip strength, gait speed, and other measures is often cumbersome in the clinical setting. The authors' primary contribution may therefore have been their use of a simple predictive scale that relies only on clinical judgment to stratify patients into 1 of 7 risk categories. To promote the common use and integration of frailty indices with popular risk models in patients with NSTEMI and unstable angina such as the Thrombolysis In Myocardial Infarction risk score, frailty assessment tools must have high interrater reliability and must be easy to use.18

Addition of Frailty and Disability to Cardiac Surgery Risk Scores Identifies Elderly Patients at High Risk of Mortality or Major Morbidity


Cardiac surgical risk scores in common use such as the EuroSCORE are known to perform less well in the elderly, in part because they do not account for important phenotypic characteristics including frailty and disability that correlate with greater adverse outcomes. The authors therefore tested the discriminative utility of 4 frailty scales (5-meter gait speed, Cardiovascular Health Study [CHS] scale, modified CHS scale, MacArthur Study of Successful Aging scale) and 3 disability scales (Katz Activities of Daily Living [ADL], Katz IADL, Nagi scale) when added to 5 cardiac surgery risk scores (Parsonnet score, Society of Thoracic Surgeons (STS)-predicted mortality and morbidity score, STS predicted mortality score, logistic EuroSCORE, age creatinine ejection fraction score) for postoperative mortality or major morbidity. Of 152 prospectively enrolled patients undergoing bypass and/or valve surgery, mean age was 75.9 years. Depending on the scale used, 20% to 46% were frail and 5% to 76% had at least 1 disability. The scales most predictive of adverse outcomes were 5-meter gait speed (odds ratio, 2.6) and greater than 3 impairments on the Nagi disability scale (odds ratio, 3). When these were added to Parsonnet and STS Mortality and Morbidity scores, model discrimination improved with the area under the curve increasing modestly from 0.68 to 0.72 to 0.73 to 0.76.


This study demonstrates the potential utility of combining markers of frailty and disability with traditional surgical risk scores. For years, these more formal markers of functional status have been largely ignored not just by the surgical community but also by practicing cardiologists when performing their preoperative assessments. Additional geriatric syndromes including hearing and vision loss, a propensity to fall, and cognitive impairment may also provide prognostic information before surgery but have not been formally evaluated with the same rigor as frailty.19

Clinical Effectiveness of Implantable Cardioverter-Defibrillators Among Medicare Beneficiaries With Heart Failure


The clinical effectiveness of implantable cardioverter-defibrillators (ICDs) in older patients with heart failure has not been established. The authors identified 4685 hospitalized patients with heart failure who were aged 65 years or older and were eligible for an ICD, had left ventricular ejection fraction of ≤35%, and were discharged alive from hospitals participating in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) and the Get With The Guidelines–Heart Failure (GWTG-HF) quality-improvement programs during the period January 1, 2003, through December 31, 2006. These patients were matched to Medicare claims to examine long-term outcomes. The main outcome measure was all-cause mortality over 3 years. Mean age was 75.2 years, 60% of the patients were women, mean ejection fraction was 25%, and 376 (8.0%) patients received an ICD before discharge. Mortality was significantly lower among patients who received an ICD before discharge compared with those who did not (19.8% versus 27.6% at 1 year, 30.9% versus 41.9% at 2 years, and 38.1% versus 52.3% at 3 years; P<0.001 for all comparisons). The inverse probability-weighted adjusted hazard of mortality at 3 years for patients receiving an ICD at discharge was 0.71.


ICD placement before discharge was associated with a mortality benefit among qualifying older persons hospitalized with heart failure. The reduced mortality rate in the group receiving an ICD was comparable to randomized, controlled trials involving younger patients.24,25 However, it is possible that the small number of patients receiving an ICD during the initial hospitalization were less acutely ill in ways not captured fully by risk adjustment and therefore would be expected to have better long-term outcomes.26

Determinants of Cardiac Catheterization Use in Older Medicare Patients With Acute Myocardial Infarction


Data have consistently demonstrated suboptimal patient selection for cardiac catheterization in acute myocardial infarction (AMI). Using data of Medicare fee-for-service beneficiaries hospitalized with AMI between 1998 and 2001, the authors developed multivariate models to determine the relative influence of anticipated benefit (baseline cardiovascular risk), anticipated harm (bleeding risk, comorbidities), and patient demographic factors (age, sex, race, regional invasive intensity) in predicting cardiac catheterization within 60 days of admission. Analyses were stratified by appropriateness criteria using American College of Cardiology/American Heart Association guidelines. Class I or II recommendations were considered appropriate, and class III recommendations were considered inappropriate. Determinants of a reduced likelihood of cardiac catheterization among the 42 241 AMI patients with appropriate indications included older age (likelihood χ2=1309.5), higher bleeding risk score (likelihood χ2=471.2), more comorbidities (likelihood χ2=276.6), female sex (likelihood χ2=162.9), hospitalization in low-intensity (likelihood χ2=67.9) or intermediate-intensity invasive regions (likelihood χ2=22.4), and baseline cardiovascular risk (likelihood χ2=6.4) (all P≤0.01). Among 2398 AMI patients with inappropriate indications, significant determinants of greater procedure likelihood included younger age, male sex, lower bleeding risk score, and fewer comorbidities.


The authors have illustrated that the anticipated harm from cardiac catheterization often takes precedence over the potential procedural benefits in typical clinical decision-making for high-risk patients. Because practice guidelines are often developed from data drawn from randomized trials that usually enroll low-risk patients, it is uncertain as to how these results generalize to patient mix in the real world. In the absence of further studies among high-risk patients, recommendations to practitioners should highlight potential procedural benefits, not just harms, in high-risk patients.23

Operative and Middle-Term Results of Cardiac Surgery in Nonagenarians: A Bridge Toward Routine Practice


Nonagenarians are among the fastest-growing sectors of the population, yet cardiac surgical outcomes in this group are relatively unknown. The authors therefore analyzed the operative and 5-year follow-up results of 127 patients aged 90 years or above who underwent cardiac surgery from 1998 to 2008. Mean age was 92 years (range, 90–103). Operative mortality was 13% as opposed to the expected 21% predicted by the logistic EuroSCORE. Higher overall mortality was seen among patients having nonelective surgery; 43% had postoperative complications such as surgical revision for bleeding, postoperative respiratory insufficiency, acute renal failure, neurological complications, and sternal wound infection. Mean hospitalization time of those surviving the initial surgery was 29.2 days (range, 16–68 days), which included postoperative cardiac rehabilitation. Five-year mortality among patients surviving the initial operation was 41%.


Although the authors emphasize the potential benefits of cardiac surgery among appropriately selected nonagenarians, both postoperative complications and mortality within 5 years of surgery were extremely common. In addition, average postoperative hospitalization time even among survivors was approximately 1 month. Although not directly reported, time spent in skilled nursing facilities probably was substantial. To support patient-centered decision-making, information on expected postoperative complications and hospital stay should become a standard part of preoperative patient education and informed consent.27

Aortic Valve Replacement in the Elderly: Determinants of Late Outcome


Few data exist on long-term outcomes of elderly patients after aortic valve replacement. The authors retrospectively evaluated 2890 consecutive patients >70 years of age who underwent aortic valve replacement between January 1993 and December 2007 and stratified them by preoperative and intraoperative variables. They used the Olmsted County, Minnesota, general population database for comparative survival analysis. Observed 5-, 10-, and 15-year late postoperative survival rates were lower than those of an age- and sex-matched healthy population (68%, 34%, and 8% versus 70%, 42% and 20%, respectively). Independent predictors of late death included older age, renal failure, diabetes mellitus, stroke, myocardial infarction, immunosuppression, prior coronary artery bypass grafting, implanted pacemaker, lower ejection fraction, hypertension, and New York Heart Association class III or IV. After stratification by an age-comorbidity risk score developed on the basis of a multivariate Cox regression model, 10-year survival for the lowest-risk group (n=946) was similar to expected survival (55% versus 55%), but, for the highest-risk group (n=564), survival was significantly lower than expected (9% versus 26%). For 229 pairs of propensity-matched patients with mechanical or biological prostheses, survival was not significantly different (67%, 40%, and 19% versus 71%, 45%, and 7% at 5, 10, and 15 years, respectively; P<0.81). Structural deterioration of bioprostheses occurred in only 64 patients (2.4%).


Choice of optimal surgical strategy for aortic valve replacement in the elderly has tended to favor bioprosthetic compared with mechanical valves because of increased risk of major hemorrhagic or embolic events associated with the latter. The low rates of structural deterioration with aortic bioprosthesis and comparable survival associated with either valve category are reassuring findings for continued use of bioprosthetic valves among older patients.28

Influence of Age on Perioperative Complications Among Patients Undergoing Implantable Cardioverter-Defibrillators for Primary Prevention in the United States


The authors examined data on periprocedural complications associated with implantable cardioverter-defibrillator (ICD) implantation for primary prevention among older persons in the United States. Using the National Cardiovascular Data Registry, the authors identified 150 264 patients who received an ICD from January 2006 to December 2008. The primary end point was any adverse event or death during hospitalization. Secondary end points included major adverse events, minor adverse events, and length of stay. Of 150 264 patients, 61% (n=91 863) were 65 years and older. A higher proportion of patients ≥65 years of age had diabetes, congestive heart failure, atrial fibrillation, renal disease, and coronary artery disease. The rate of adverse events or death was 2.8%, 3.1%, 3.5%, 3.9%, 4.5%, and 4.5%, respectively in patients under 65 years, 65- to 69-year-olds, 70- to 74-year-olds,75- to 79-year-olds, 80- to 84-year-olds, and patients 85 years and older. After adjustment for clinical covariates, multivariate analysis found a significantly increased odds (P≤0.05) of any adverse event or death among 75- to 79-year-olds (odds ratio [OR], 1.14), 80- to 84-year-olds (OR, 1.22), and patients 85 years and older (OR, 1.15), compared with patients under 65 years of age.


Age remains a prognostic factor for periprocedural complications related to ICD placement. Patients should be made aware of how their individual risk changes due to age and other prognostic factors before device placement. Implementation of point-of-care tools that accurately describe procedural risks based on individual patient characteristics should be a priority to promote evidence-based decision-making.29

Survival After Open Versus Endovascular Thoracic Aortic Aneurysm Repair in an Observational Study of the Medicare Population


The authors of the study compared the short- and long-term survival of patients with descending thoracic aortic aneurysms (TAAs) after open and endovascular repair (TEVAR). By using a combination of procedural and diagnostic International Classification of Disease, 9th Revision codes, the authors analyzed patients who underwent repair for intact as well as ruptured TAAs using Medicare claims from 1998 to 2007. They examined perioperative mortality (death occurring before hospital discharge or within 30 days) and 5-year survival across repair type (open repair or TEVAR) in crude, adjusted (for age, sex, race, procedure year, and Charlson comorbidity score), and propensity-matched cohorts. Overall, 12 573 Medicare patients underwent open repair and 2732 patients underwent TEVAR. Perioperative mortality was lower in patients undergoing TEVAR compared with open repair for both intact (6.1% versus 7.1%; P=0.07) and ruptured (28% versus 46%; P<0.0001) TAA. However, patients with intact TAA who underwent TEVAR had significantly worse survival than open patients at 1 year (87% for open, 82% for TEVAR; P=0.001) and 5 years (72% for open; 62% for TEVAR; P

Frailty and Cardiovascular Disease

Chronological age does not always reflect biological status, which may vary from robust to frail. This concept of “frailty” among older patients with cardiovascular disease has emerged primarily from the geriatrics literature, where frailty is considered a biological state characterized by increased vulnerability and decreased resistance to physiological stressors.13–15 From a syndromic perspective, frailty is associated with loss of skeletal muscle mass, weight loss, reduced walking speed, exhaustion, and reduced activity.13 In recent years, this concept of frailty has been applied to patients presenting with acute cardiac illness as well as those undergoing procedural interventions such as cardiac surgery. Through these studies, it has been shown that frailty provides additional short- and long-term prognostic information above and beyond traditional demographic information and medical comorbidities.

Procedural Interventions in the Elderly

Cardiovascular disease is the leading cause of morbidity and mortality in older persons. Accordingly, a significant proportion of the elderly receive invasive cardiovascular interventions such percutaneous coronary interventions (PCIs) or implantation of a cardioverter-defibrillator (ICD). A quarter of PCIs are performed in patients above the age of 75 years, and almost half of the ICD recipients are above the age of 70 years.20–22 Yet, despite the widespread application of these interventions, we lack a detailed understanding regarding their precise effectiveness as well as anticipated harm in older persons, especially the “oldest old” (persons above the age of 85 years). This group has been largely excluded from clinical trials and has often been passed over for treatment even in the real world, as perceived harms have affected treatment decisions to a greater degree than anticipated absolute benefits.23

In the following section, we include a variety of studies looking at procedural interventions in the elderly, including transcatheter aortic valve replacement, implantation of a cardioverter-defibrillator, and abdominal aneurysm repair.

Marjorie Bastien | Paul Poirier | Isabelle Lemieux | Jean Pierre Després

The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the 'obesity paradox', which associates better survival and fewer cardiovascular (CV) events in patients with elevated BMI afflicted with chronic diseases compared to non-obese patients. However, BMI cannot make the distinction between an elevated body weight due to high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently associated with metabolic abnormalities than a high level of lean body mass. Another explanation for the paradox is the absence of control for major individual differences in regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate of excess dietary lipids, which may determine whether or not body homeostasis will be maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity, also induces a variety of structural adaptations/alterations in CV structure/function. Adipose tissue can now be considered as an endocrine organ orchestrating crucial interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle, the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity. © 2014 Elsevier Inc.

Vaughn W. Barry | Meghan Baruth | Michael W. Beets | J. Larry Durstine | Jihong Liu | Steven N. Blair

The purpose of this study was to quantify the joint association of cardiorespiratory fitness (CRF) and weight status on mortality from all causes using meta-analytical methodology. Studies were included if they were (1) prospective, (2) objectively measured CRF and body mass index (BMI), and (3) jointly assessed CRF and BMI with all-cause mortality. Ten articles were included in the final analysis. Pooled hazard ratios were assessed for each comparison group (i.e. normal weight-unfit, overweight-unfit and -fit, and obese-unfit and -fit) using a random-effects model. Compared to normal weight-fit individuals, unfit individuals had twice the risk of mortality regardless of BMI. Overweight and obese-fit individuals had similar mortality risks as normal weight-fit individuals. Furthermore, the obesity paradox may not influence fit individuals. Researchers, clinicians, and public health officials should focus on physical activity and fitness-based interventions rather than weight-loss driven approaches to reduce mortality risk. © 2014 Elsevier Inc.

Damon L. Swift | Neil M. Johannsen | Carl J. Lavie | Conrad P. Earnest | Timothy S. Church

This review explores the role of physical activity (PA) and exercise training (ET) in the prevention of weight gain, initial weight loss, weight maintenance, and the obesity paradox. In particular, we will focus the discussion on the expected initial weight loss from different ET programs, and explore intensity/volume relationships. Based on the present literature, unless the overall volume of aerobic ET is very high, clinically significant weight loss is unlikely to occur. Also, ET also has an important role in weight regain after initial weight loss. Overall, aerobic ET programs consistent with public health recommendations may promote up to modest weight loss (~. 2. kg), however the weight loss on an individual level is highly heterogeneous. Clinicians should educate their patients on reasonable expectations of weight loss based on their physical activity program and emphasize that numerous health benefits occur from PA programs in the absence of weight loss. © 2014 Elsevier Inc.

Jonathan Myers | Paul McAuley | Carl J. Lavie | Jean Pierre Despres | Ross Arena | Peter Kokkinos

© 2014. The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity.

Miguel A. Martínez-González | Jordi Salas-Salvadó | Ramón Estruch | Dolores Corella | Montse Fitó | Emilio Ros

© 2015 Elsevier Inc. The PREDIMED (PREvención con DIeta MEDiterránea) multicenter, randomized, primary prevention trial assessed the long-term effects of the Mediterranean diet (MeDiet) on clinical events of cardiovascular disease (CVD). We randomized 7447 men and women at high CVD risk into three diets: MeDiet supplemented with extra-virgin olive oil (EVOO), MeDiet supplemented with nuts, and control diet (advice on a low-fat diet). No energy restriction and no special intervention on physical activity were applied. We observed 288 CVD events (a composite of myocardial infarction, stroke or CVD death) during a median time of 4.8. years; hazard ratios were 0.70 (95% CI, 0.53-0.91) for the MeDiet + EVOO and 0.70 (CI, 0.53-0.94) for the MeDiet + nuts compared to the control group. Respective hazard ratios for incident diabetes (273 cases) among 3541 non-diabetic participants were 0.60 (0.43-0.85) and 0.82 (0.61-1.10) for MeDiet + EVOO and MeDiet. +. nuts, respectively versus control. Significant improvements in classical and emerging CVD risk factors also supported a favorable effect of both MeDiets on blood pressure, insulin sensitivity, lipid profiles, lipoprotein particles, inflammation, oxidative stress, and carotid atherosclerosis. In nutrigenomic studies beneficial effects of the intervention with MedDiets showed interactions with several genetic variants (TCF7L2, APOA2, MLXIPL, LPL, FTO, M4CR, COX-2, GCKR and SERPINE1) with respect to intermediate and final phenotypes. Thus, the PREDIMED trial provided strong evidence that a vegetable-based MeDiet rich in unsaturated fat and polyphenols can be a sustainable and ideal model for CVD prevention.

Susan A. Carlson | Janet E. Fulton | Michael Pratt | Zhou Yang | E. Kathleen Adams

© 2014. This study estimates the percentage of health care expenditures in the non-institutionalized United States (U.S.) adult population associated with levels of physical activity inadequate to meet current guidelines. Leisure-time physical activity data from the National Health Interview Survey (2004-2010) were merged with health care expenditure data from the Medical Expenditure Panel Survey (2006-2011). Health care expenditures for inactive (i.e., no physical activity) and insufficiently active adults (i.e., some physical activity but not enough to meet guidelines) were compared with active adults (i.e., ≥. 150. minutes/week moderate-intensity equivalent activity) using an econometric model. Overall, 11.1% (95% CI: 7.3, 14.9) of aggregate health care expenditures were associated with inadequate physical activity (i.e., inactive and insufficiently active levels). When adults with any reported difficulty walking due to a health problem were excluded, 8.7% (95% CI: 5.2, 12.3) of aggregate health care expenditures were associated with inadequate physical activity. Increasing adults' physical activity to meet guidelines may reduce U.S. health care expenditures.

Estefania Oliveros | Virend K. Somers | Ondrej Sochor | Kashish Goel | Francisco Lopez-Jimenez

Individuals with normal body weight by body mass index (BMI) and high body fat percentage show a high degree of metabolic dysregulation. This phenomenon, defined as normal weight obesity, is associated with a significantly higher risk of developing metabolic syndrome, cardiometabolic dysfunction and with higher mortality. Recently, we have also shown that coronary artery disease patients with normal BMI and central obesity have the highest mortality risk as compared to other adiposity patterns. Therefore, it is important to recognize these high-risk groups for better adiposity-based risk stratification. There is a need for an updated definition of obesity based on adiposity, not on body weight. © 2014 Elsevier Inc.

Jongha Park | Seyed Foad Ahmadi | Elani Streja | Miklos Z. Molnar | Katherine M. Flegal | Daniel Gillen | Csaba P. Kovesdy | Kamyar Kalantar-Zadeh

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients w ith end-stage renal disease (ESRD), however, an "obesity paradox" or "reverse epidemiology" (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. © 2014 Elsevier Inc.

Martin A. Alpert | Jad Omran | Ankit Mehra | Sivakumar Ardhanari

Obesity, particularly severe obesity is capable of producing hemodynamic alterations that predispose to changes in cardiac morphology and ventricular function. These include increased cardiac output, left ventricular hypertrophy and diastolic and systolic dysfunction of both ventricles. Facilitated by co-morbidities such as hypertension, the sleep apnea/obesity hypoventilation syndrome, and possibly certain neurohormonal and metabolic alterations, these abnormalities may predispose to left and right heart failure, a disorder known as obesity cardiomyopathy. © 2014 Elsevier Inc.

Robert Sallis | Barry Franklin | Liz Joy | Robert Ross | David Sabgir | James Stone

© 2014 Elsevier Inc. The time has come for healthcare systems to take an active role in the promotion of physical activity (PA). The connection between PA and health has been clearly established and exercise should be viewed as a cost effective medication that is universally prescribed as a first line treatment for virtually every chronic disease. While there are potential risks associated with exercise, these can be minimized with a proper approach and are far outweighed by the benefits. Key to promoting PA in the clinical setting is the use of a PA Vital Sign in which every patient's exercise habits are assessed and recorded in their medical record. Those not meeting the recommended 150. min per week of moderate intensity PA should be encouraged to increase their PA levels with a proper exercise prescription. We can improve compliance by assessing our patient's barriers to being more active and employing new and evolving technology like accelerometers and smart phones applications, along with various websites and programs that have proven efficacy.

Alban De Schutter | Carl J. Lavie | Richard V. Milani

Obesity is associated with a host of cardiovascular risk factors and its prevalence is rising rapidly. Despite strong evidence that obesity predisposes to the development and progression of coronary heart disease (CHD), numerous studies have shown an inverse relationship between various measures of obesity (most commonly body mass index) and outcomes in established CHD. In this article we review the evidence surrounding the < obesity paradox. ≫ in the secondary care of CHD patients and the CHD presentations where a paradox has been found. Finally we discuss the impact of cardiorespiratory fitness and a number of mechanisms which may offer potential explanations for this puzzling phenomenon. © 2014 Elsevier Inc.

Heikki V. Huikuri | Phyllis K. Stein

Heart rate (HR) variability has been extensively studied in cardiac patients, especially in patients surviving an acute myocardial infarction (AMI) and also in patients with congestive heart failure (CHF) or left ventricular (LV) dysfunction. The majority of studies have shown that patients with reduced or abnormal HR variability have an increased risk of mortality within a few years after an AMI or after a diagnosis of CHF/LV dysfunction. Various measures of HR dynamics, such as time-domain, spectral, and non-linear measures of HR variability have been used in risk stratification. The prognostic power of various measures, except of those reflecting rapid R-R interval oscillations, has been almost identical, albeit some non-linear HR variability measures, such as short-term fractal scaling exponent have provided somewhat better prognostic information than the others. Abnormal HR variability predicts both sudden and non-sudden cardiac death. Because of remodeling of the arrhythmia substrate after AMI, early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events. Future randomized trials using HR variability/turbulence as one of the pre-defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of cardiac patients. © 2013 Elsevier Inc.

Laura F. DeFina | William L. Haskell | Benjamin L. Willis | Carolyn E. Barlow | Carrie E. Finley | Benjamin D. Levine | Kenneth H. Cooper

© 2014 Elsevier Inc. Physical activity (PA) and cardiorespiratory fitness (CRF) both have inverse relationships to cardiovascular (CV) morbidity and mortality. Recent position papers and guidelines have identified the important role of both of these factors in CV health. The benefits of PA and CRF in the prevention of CV disease and risk factors are reviewed. In addition, assessment methodology and utilization in the research and clinical arenas are discussed. Finally, the benefits, methodology, and utilization are compared and contrasted to better understand the two (partly) distinct components and their impact on CV health.

Robert F. Kushner

Obesity is one of the most serious and prevalent non-communicable diseases of the 21st century. It is also a patient-centered condition in which affected individuals seek treatment through a variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, two new pharmacological agents, phentermine-topiramate and lorcaserin, were approved in 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by comorbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss. © 2014 Elsevier Inc.

Andrew P. Hills | Donald R. Dengel | David R. Lubans

© 2014. Physical activity (PA) provides numerous physiological and psychosocial benefits. However, lifestyle changes, including reduced PA opportunities in multiple settings, have resulted in an escalation of overweight and obesity and related health problems. Poor physical and mental health, including metabolic and cardiovascular problems is seen in progressively younger ages, and the systematic decline in school PA has contributed to this trend. Of note, the crowded school curriculum with an intense focus on academic achievement, lack of school leadership support, funding and resources, plus poor quality teaching are barriers to PA promotion in schools. The school setting and physical educators in particular, must embrace their role in public health by adopting a comprehensive school PA program. We provide an overview of key issues and challenges in the area plus best bets and recommendations for physical education and PA promotion in the school system moving forward.

Adrienne L. Clark | Gregg C. Fonarow | Tamara B. Horwich

Obesity is a growing public health problem in the general population, and significantly increases the risk for the development of new-onset heart failure (HF). However, in the setting of chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared to normal-weight patients. Evidence exists for an "obesity paradox" in HF, with the majority of data measuring obesity by body mass index, but also across various less-frequently used measures of body fat (BF) and body composition including waist circumference, waist-hip ratio, skinfold estimates of percent BF, and bioelectrical impedance analysis of body composition. Other emerging areas of investigation such as the relationship of the obesity paradox to cardiorespiratory fitness are also discussed. Finally, this review explores various explanations for the obesity paradox, and summarizes the current evidence for intentional weight loss treatments for HF in context. © 2014 Elsevier Inc.

Larkin Elderon | Mary A. Whooley

Approximately one out of every five patients with cardiovascular disease (CVD) suffers from major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for CVD incidence, severity and outcomes. Great progress has been made in understanding potential mediators between MDD and CVD, particularly focusing on health behaviors. Investigators have also made considerable strides in the diagnosis and treatment of depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD. © 2013.

Carl J. Lavie | Alban De Schutter | Parham Parto | Eiman Jahangir | Peter Kokkinos | Francisco B. Ortega | Ross Arena | Richard V. Milani

© 2016 Elsevier Inc. The prevalence and severity of obesity have increased in the United States and most of the Westernized World over recent decades, reaching worldwide epidemics. Since obesity worsens most of the cardiovascular disease (CVD) risk factors, not surprisingly, most CVDs, including hypertension, coronary heart disease, heart failure, and atrial fibrillation, are all increased in the setting of obesity. However, many studies and meta-analyses have demonstrated an obesity paradox with regards to prognosis in CVD patients, with often the overweight and mildly obese having a better prognosis than do their leaner counterparts with the same CVD. The implication for fitness to markedly alter the relationship between adiposity and prognosis and the potential impact of weight loss, in light of the obesity paradox, are all reviewed.

Andrew Moran | Mohammad Forouzanfar | Uchechukwu Sampson | Sumeet Chugh | Valery Feigin | George Mensah

The epidemiology of cardiovascular diseases in sub-Saharan Africa is unique among world regions, with about half of cardiovascular diseases (CVDs) due to causes other than atherosclerosis. CVD epidemiology data are sparse and of uneven quality in sub-Saharan Africa. Using the available data, the Global Burden of Diseases, Risk Factors, and Injuries (GBD) 2010 Study estimated CVD mortality and burden of disease in sub-Saharan Africa in 1990 and 2010. The leading CVD cause of death and disability in 2010 in sub-Saharan Africa was stroke; the largest relative increases in CVD burden between 1990 and 2010 were in atrial fibrillation and peripheral arterial disease. CVD deaths constituted only 8.8% of all deaths and 3.5% of all disability-adjusted life years (DALYs) in sub-Sahara Africa, less than a quarter of the proportion of deaths and burden attributed to CVD in high income regions. However, CVD deaths in sub-Saharan Africa occur at younger ages on average than in the rest of the world. It remains uncertain if increased urbanization and life expectancy in some parts of sub-Saharan African nations will transition the region to higher CVD burden in future years. © 2013 Elsevier Inc.

Lior Bibas | Michael Levi | Melissa Bendayan | Louis Mullie | Daniel E. Forman | Jonathan Afilalo

© 2014 Elsevier Inc. The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations.

Ian M. Kronish | Siqin Ye

Approximately 50% of patients with cardiovascular disease and/or its major risk factors have poor adherence to their prescribed medications. Finding novel methods to help patients improve their adherence to existing evidence-based cardiovascular drug therapies has enormous potential to improve health outcomes while potentially reducing health care costs. The goal of this report is to provide a review of the current understanding of adherence to cardiovascular medications from the point of view of prescribing clinicians and cardiovascular researchers. Key topics addressed include: 1) definitions of medication adherence; 2) prevalence and impact of non-adherence; 3) methods for assessing medication adherence; 4) reasons for poor adherence; and 5) approaches to improving adherence to cardiovascular medications. For each of these topics, the report seeks to identify important gaps in knowledge and opportunities for advancing the field of cardiovascular adherence research. © 2013 Elsevier Inc.

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