Myocardial Infarction In Older Adults Research Articles

Characteristics and Prognosis of Type 2 Myocardial Infarction Through Worsening Renal Function and NT-proBNP in Older Adults with Pneumonia.

Type 2 myocardial infarction (MI) is becoming more recognized. This study aimed to assess the factors linked to type 2 MI in older adults with pneumonia and further determine the predictive factors of 90-day adverse events (refractory heart failure, cardiogenic shock, and all-cause mortality). A single-center retrospective analysis was conducted among older adults with pneumonia. The primary outcome was the prevalence of type 2 MI. The secondary objective was to assess the adverse events in these patients with type 2 MI within 90 days. A total of 2618 patients were included. Of these, 361 patients (13.8%) suffered from type 2 MI. Multivariable predictors of type 2 MI were chronic kidney disease (CKD), age-adjusted Charlson comorbidity index (ACCI) score, and NT-proBNP > 4165pg/mL. Moreover, the independent predictive factors of 90-day adverse events included NT-proBNP > 4165pg/mL, age, ACCI score, and CKD. The Kaplan-Meier adverse events curves revealed that the type 2 MI patients with CKD and NT-proBNP > 4165pg/mL had a higher risk than CKD or NT-proBNP > 4165pg/mL alone. Type 2 MI in older pneumonia hospitalization represents a heterogeneous population. Elevated NT-proBNP level and prevalence of CKD are important predictors of type 2 MI and 90-day adverse events in type 2 MI patients.

Associations between Body Mass Index, Waist Circumference, and Myocardial Infarction in Older Adults Aged over 75 Years: A Population-Based Cohort Study.

Background and Objectives: Body mass index (BMI) is widely used as a standard screening method for obesity and an indicator of related diseases. However, its inability to distinguish between lean body mass and body fat limits its utility. This limitation may be more prominent in older populations, wherein age-related sarcopenia and increased visceral fat due to the redistribution of adipose tissue may preclude a precise estimation of obesity. Many studies suggest that waist circumference (WC) is more strongly related to obesity-related diseases. There are also different opinions on whether the obesity paradox is real or a result of confusing interpretations. This study seeks to determine the association between myocardial infarction (MI), BMI, and WC in older adults and to determine if BMI and WC can reliably predict the risk of cardiovascular disease. Materials and Methods: We conducted a cohort study of older Korean adults aged over 75 years registered in the National Health Insurance System Senior database. Results: The results from the analysis using model 5, which was adjusted for each study variable, showed that the lower the BMI, the higher the hazard ratio (HR) of MI and vice versa. On the other hand, groups with lower than normal WC showed lower HR; even if it was higher, the difference was not statistically significant. Those with abdominal obesity tended to have an increased HR of MI. Conclusions: This study found that HR for MI has a negative relationship with BMI, whereas it has a positive relationship with WC. Furthermore, WC is a more appropriate indicator for predicting the risk of MI in the older population.

Sex Differences and Temporal Trends in Revascularization and Outcomes of ST-Elevation Myocardial Infarction in Older Adults in the United States

Previous studies have suggested that in-hospital mortality is higher in younger women with ST-segment elevation myocardial infarction (STEMI) than in men. However, more coronary artery disease diagnoses occurred in patients older than 60 years. This study sought to investigate the temporal trends and sex differences in revascularization and in-hospital outcomes in older STEMI patients. National Inpatient Sample databases from 2005-2014 were utilized to identify all STEMI patients with age greater than 60 years old. We studied the temporal trends and sex differences in revascularization therapies and in-hospital mortality. From 2005-2014, there were 192,204 older adults diagnosed with STEMI. Older women with STEMI were less likely to receive reperfusion (percutaneous coronary intervention (PCI) adjusted OR: 0.90; 95% CI: 0.87-0.92) compared to older men. Also, the adjusted odds ratio comparing the likelihood of receiving PCI between women and men decreased by an annual average of 0.9% (p=0.028). Older women had higher in-hospital mortality than men (adjusted OR: 1.12; 95% CI: 1.08 to 1.17). There was no significant change of adjusted in-hospital mortality in both genders (all p >0.05). Older women were less likely to receive revascularization for STEMI, and this gap was increasing during the study period. Older women had higher in-hospital mortality as compared with older men, but there was no significant temporal change for both genders. These findings present an opportunity to bridge the gender-gap in providing care to older patients with STEMI.

Sex Differences in Cardiovascular Outcomes of Older Adults After Myocardial Infarction.

BackgroundEvidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long‐term cardiovascular outcomes after MI in older adults.Methods and ResultsAll patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10‐year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10‐year follow‐up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST‐segment–elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high‐dose statins were more frequently used by men, and renin‐angiotensin‐aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10‐year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13–1.21; P<0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P<0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P=0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P<0.0001) were more frequent in men during long‐term follow‐up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non‐revascularized patients, and in patients 70 to 79 and ≥80 years.ConclusionsOlder men had higher long‐term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence‐based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.

Abstract 17438: Sex Differences and Temporal Trends in Revascularization and Outcomes of ST-Elevation Myocardial Infarction in Older Adults in the United States

Background: Prior studies have suggested that women with ST-elevation myocardial infarction (STEMI) have higher in-hospital mortality risk than younger men with STEMI. However, there is a significant STEMI risk in older patients. We analyzed temporal trends and sex differences in revascularization and other in-hospital outcomes in older STEMI patients. Methods: National Inpatient Sample databases from 2005 to 2014 were utilized to identify all STEMI patients with age greater than 60 years old. We studied the temporal trends and sex differences in revascularization therapies and in-hospital mortality. Results: There were N=192,204 older adults diagnosed with STEMI. Older women with STEMI were less likely to undergo coronary angiography (adjusted OR: 0.90; 95% CI: 0.88 to 0.93) and receive reperfusion (percutaneous coronary intervention (PCI) adjusted OR: 0.90; 95% CI: 0.87 to 0.92) compared to older men. Also, the adjusted odds ratio comparing the likelihood of receiving PCI between women and men decreased by an annual average of 0.9% (P=0.028). Older men were more likely to receive PCI on Hospital Day 0 compared to older women. There was a decreasing trend in both sexes for use of coronary artery bypass graft (CABG), though older men consistently underwent CABG more often than older women (Figure). Older women had higher in-hospital mortality than men (adjusted OR: 1.12; 95% CI: 1.08 to 1.17). However, the differences decreased with increasing patient age. There was no significant change in adjusted in-hospital mortality in both genders (all P&gt;0.05). Conclusions: Older women were less likely to receive revascularization for STEMI than men, and this gap increased over the study period. Older women had higher in-hospital mortality compared with older men, but there was no significant temporal change for both genders. Further research is needed to identify the reasons why older women receive less revascularization.

Exposure to guideline-recommended drugs after a first acute myocardial infarction in older adults: does deprivation matter?

Inequities between guideline-recommended drugs (GRD) exposure and socioeconomic status might exist. The objective was to assess the association between a material and a social deprivation index and GRD exposure following a first acute myocardial infarction (AMI) in older adults in the province of Quebec. We conducted a retrospective cohort study using the Quebec Integrated Chronic Disease Surveillance System. Elderly ≥66 years, hospitalized for a first AMI between January 1, 2006, and December 31, 2011 and covered by the public drug plan were identified. Exposure to GRD (i.e. simultaneous use of 1) antiplatelet, 2) beta-blocker, 3) lipid-lowering and 4) angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker drugs) was assessed 30 and 365 days following hospital discharge. Associations between deprivation index and GRD exposure were estimated with log-binomial regressions adjusting for potential confounders. Exposure to GRD was 52.2% and 48.0%, 30 and 365 days after hospital discharge, respectively. No statistically significant association was observed in multivariate analysis for both time points. Thirty days post hospital discharge, adjusted prevalence ratio of non-exposure to GRD was 0.98 (95% confidence interval [CI]: 0.95-1.02) for most materially deprived vs. least deprived and 1.04 (95% CI: 0.99-1.08) for most socially deprived vs. least deprived. Similar results were observed for 365 days. Exposure to GRD after a first urgent AMI among older adults insured by the public drug plan in the province of Quebec is relatively low. Reasons and risk groups for this low exposure should be studied to improve secondary prevention. However, results suggest equitable access to GRD, regardless of deprivation.

P6206Death, debility, and destitution following recurrent myocardial infarction in older adults

Abstract Background Most prior research on outcomes among older adults with established cardiovascular diseases focuses on recurrent events and hospitalizations. However, older adults value financial security and functional independence in addition to these disease-focused metrics. Recurrent cardiovascular events may increase risk of long-term nursing home residence and financial strain. Purpose To compare the risk for death, debility (long-term residence in a nursing home), and destitution (eligibility for health insurance programs for impoverished individuals) among older adults with recurrent myocardial infarction (MI) and controls. Methods We conducted a retrospective cohort study using administrative data from the United States Medicare program, a health insurance program for older adults. Among all patients who experienced a first overnight hospitalization with a discharge diagnosis of MI between 1 January 2007 and 30 June 2016, we identified patients with a recurrent MI hospitalization. Additionally, we selected controls from the same population of patients with MI, matched on calendar year of the initial MI and days since the initial MI. We included 194,481 patients aged 66 years and older with recurrent MI hospitalizations and 777,924 controls. Patients were followed for death, debility, and destitution until 31 December 2016. We used Kaplan-Meier curves and Cox proportional hazards models adjusted for sociodemographic factors, comorbidities, and healthcare utilization to compare patients with recurrent MI and matched controls. Results The average age of the population was 80.0 (standard deviation 8.3) years and 56.7% were women. Patients with recurrent MI were more likely to have a history of diabetes, chronic kidney disease, heart failure and peripheral artery disease than controls. The cumulative incidence of death, debility, and destitution were all higher among patients with recurrent MI than their matched controls (Figure). Comparing patients with recurrent MI to controls, the hazard ratios (95% confidence intervals) were 2.11 (2.09–2.13) for death, 0.92 (0.89–0.94) for debility, and 1.34 (1.29–1.39) for destitution after multivariable adjustment. Death, debility, and destitution Conclusion Preventing recurrent MIs has the potential to reduce not only mortality but also destitution. Acknowledgement/Funding Amgen, Inc

Mild Cognitive Impairment and Receipt of Treatments for Acute Myocardial Infarction in Older Adults.

Older adults with mild cognitive impairment (MCI) should receive evidence-based treatments when indicated. Providers and patients may overestimate the risk of dementia in patients with MCI leading to potential under-treatment. However, the association between pre-existing MCI and receipt of evidence-based treatments is uncertain. To compare receipt of treatments for acute myocardial infarction (AMI) between older adults with pre-existing MCI and cognitively normal patients. Prospective study using data from the nationally representative Health and Retirement Study, Medicare, and American Hospital Association. Six hundred nine adults aged 65 or older hospitalized for AMI between 2000 and 2011 and followed through 2012 with pre-existing MCI (defined as modified Telephone Interview for Cognitive Status score of 7-11) and normal cognition (score of 12-27). Receipt of cardiac catheterization and coronary revascularization within 30days and cardiac rehabilitation within 1year of AMI hospitalization. Among the survivors of AMI, 19.2% had pre-existing MCI (55.6% were women and 44.4% were male, with a mean [SD] age of 82.3 [7.5]years), and 80.8% had normal cognition (45.7% were women and 54.3% were male, with a mean age of 77.1 [7.1]years). Survivors of AMI with pre-existing MCI were significantly less likely than those with normal cognition to receive cardiac catheterization (50% vs 77%; P < 0.001), coronary revascularization (29% vs 63%; P < 0.001), and cardiac rehabilitation (9% vs 22%; P = 0.001) after AMI. After adjusting for patient and hospital factors, pre-existing MCI remained associated with lower use of cardiac catheterization (adjusted hazard ratio (aHR), 0.65; 95% CI, 0.48-0.89; P = 0.007) and coronary revascularization (aHR, 0.55; 95% CI, 0.37-0.81; P = .003), but not cardiac rehabilitation (aHR, 1.01; 95% CI, 0.49-2.07; P = 0.98). Pre-existing MCI is associated with lower use of cardiac catheterization and coronary revascularization but not cardiac rehabilitation after AMI.

Incidence and mortality of myocardial infarction among Catalonian older adults with and without underlying risk conditions: The CAPAMIS study.

Population-based data about the epidemiology of acute myocardial infarction is limited. This study investigated incidence and mortality of acute myocardial infarction in older adults with specific underlying chronic conditions and evaluated the influence of these conditions in developing acute myocardial infarction. This was a population-based cohort study involving 27,204 individuals ≥ 60 years of age in Tarragona (Catalonia, Spain). Data on all cases of hospitalised acute myocardial infarction were collected from 1 December 2008-30 November 2011. Incidence rates and 30-day mortality were estimated according to age, sex, chronic illnesses and underlying conditions. Multivariable Cox regression analysis was used to calculate hazard ratios and to estimate the association between baseline conditions and risk of developing acute myocardial infarction. The incidence of acute myocardial infarction was 475 per 100,000 person-years. Maximum rates appeared among individuals with history of coronary artery disease (2839 per 100,000), chronic severe nephropathy (1407 per 100,000), atrial fibrillation (1226 per 100,000), chronic heart disease (1149 per 100,000), history of stroke (1147 per 100,000) and diabetes mellitus (914 per 100,000). Thirty-day mortality was 15.3% overall, reaching 31.6% among patients over 80 years. In the multivariable analysis, history of coronary artery disease, age > 70 years, sex male, chronic heart disease, history of stroke, atrial fibrillation, diabetes mellitus and hypertension emerged as significantly associated with an increased risk of acute myocardial infarction. The incidence and mortality of acute myocardial infarction remain considerable in our setting. Considering classical major risk factors, diabetes mellitus and hypertension were the underlying conditions most strongly associated with an increased risk in our study population.

Gout and the risk of myocardial infarction in older adults: a study of Medicare recipients

BackgroundCurrent evidence suggests that gout is independently associated with a higher risk of myocardial infarction (MI), but data in older adults at the highest risk of MI are lacking. Our objective was to examine whether gout is associated with a higher risk of incident MI in older adults.MethodsWe assessed the 2006–2012 Medicare 5% claims data for the association of gout at baseline with the occurrence of a new (incident) MI during follow-up (no diagnosis of MI in the baseline period of at least 1 year), adjusting for patient demographics, medical comorbidity (Charlson–Romano index), and commonly used cardiovascular and gout medications, in a Cox proportional hazards model. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.ResultsIn a cohort of 1,733,613 eligible people, 14,279 developed incident MI: 13,029 MIs in people without gout and 1250 MIs in those with gout, with crude incident rates of 1.3 vs 4.1 per 1000 person-years, respectively. In multivariable-adjusted analyses, gout was significantly associated with a higher hazard of incident MI, with HR of 2.08 (95% CI 1.95, 2.21). Risk was minimally attenuated in sensitivity analyses that replaced the continuous Charlson–Romano index score with a categorical score or individual comorbidities, or expanding to a more sensitive diagnostic algorithm for incident MI, or additionally adjusting for obesity.ConclusionsGout was independently associated with a higher risk of MI in the elderly, aged 65 years or older. The role of inflammatory and other pathways need to be explored as underlying mechanisms for this association.

Risk Stratification for Older Adults with Myocardial Infarction

Older adults presenting with an acute myocardial infarction (MI) have an increased morbidity and mortality as compared to younger adults. The management of MI in older adults is dependent on accurate risk stratification incorporating the vast patient heterogeneity characteristic of this population. Traditional risk stratification methods differ in their predictive validity as age increases and important geriatric risk factors such as multimorbidity and geriatric syndromes (e.g., frailty) are often not taken into consideration when developing patient-centered care plans. The dearth of specific clinical practice guidelines for this population, due in part to the exclusion of representative older adults in clinical trials, has resulted in elderly patients with an MI receiving evidence based reperfusion and secondary prevention therapies at much lower rates compared to their younger counterparts. Recent developments in geriatric cardiology have begun to identify and address these gaps, but much evidence still needs to be established in this area.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults

Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged ≥66years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. Over 25% of beneficiaries were aged ≥85years, 55% were women, and 89% were white. Comorbidities were common, including diabetes (22.9%), hypertension (46.7%), heart failure (10.3%), and chronic obstructive pulmonary disease (19.2%). Following AMI, 16,078 beneficiaries (20.6%) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9% had ≥2 CHD rehospitalizations (n = 5773, 7.4% of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age ≥85years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI.

Protective Effect of Regular Physical Activity on Depression After Myocardial Infarction: The HUNT Study

PurposeTo study if physical activity within the recommended level over time was associated with risk of developing depression after the first myocardial infarction in older adults. MethodsMen (n = 143) and women (n = 46) who had reached the age of 60 years in 2006-2008 who participated in the Nord-Trøndelag Health Study (HUNT1, 1984-1986; HUNT2, 1995-1997; HUNT3, 2006-2008) without any mental illness or cardiovascular disease at baseline in HUNT2 and who experienced their first myocardial infarction before HUNT3 were included. Based on the patterns of physical activity from HUNT1 to HUNT2, the sample was divided into 4 groups: persistently inactive, from active to inactive, from inactive to active, and persistently active. The primary outcome, post-myocardial infarction depression symptoms, was measured with the Hospital, Anxiety and Depression Scale in HUNT3. ResultsIn HUNT3, 11% of participants had depression. After multivariable adjustment, those who were persistently active had significantly lower odds of being depressed (odds ratio 0.28; 95% confidence interval, 0.08-0.98) compared with those who were persistently inactive. Additionally, a significant test for trend (P = .033) of lowering odds of depression was observed across all 4 categories of physical activity patterns at baseline. ConclusionsIn this small sample of initially healthy adults, we observed a long-term protective effect of regular physical activity on the development of depression following myocardial infarction.

Atrial fibrillation and incident myocardial infarction in the elderly.

Atrial fibrillation (AF) has been shown to be independently associated with an increased risk of myocardial infarction (MI) in a predominantly middle-aged population; however, this association has not been examined in older populations. AF is associated with MI in older adults. A total of 4608 participants (85% white, 40% male) from the Cardiovascular Health Study without evidence of baseline coronary heart disease were included in this analysis. AF cases were identified during the yearly study electrocardiogram, a self-reported history of a physician diagnosis, or by hospitalization data. Incident MI was identified using medical records with local and central adjudication. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AF and incident MI. A total of 434 (9.4%) participants had evidence of AF before incident MI. Over a median follow-up of 12.2 years, a total of 797 (17.3%) participants developed MI. In a multivariable Cox proportional hazards analysis adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, AF was associated with an increased risk of MI (HR: 1.7, 95% CI: 1.4-2.2). A significant interaction was detected by race, with black (HR: 3.1, 95% CI: 1.7-5.6) AF participants having an increased risk of MI compared with whites (HR: 1.6, 95% CI: 1.2-2.1; P interaction = 0.030). AF is associated with an increased risk of MI in a population of older adults.

Research on Multiple Chronic Conditions

Research on Multiple Chronic Conditions

β-blocker therapy after acute myocardial infarction

Evaluation of: Zuckerman IH, Yin X, Rattinger GB et al. Effect of exposure to evidence-based pharmacotherapy on outcomes after acute myocardial infarction in older adults. J. Am. Geriatr. Soc. 60(10), 1854–1861 (2012).The number of myocardial infarctions (MIs) in population remains high and this event is a significant predictor of mortality. Information in literature points to a reduction in mortality, reinfarction and sudden death in first year, especially in patients with high risk, if β-blockers (BBs) are used after MI. In a perspective study, Zuckerman et al. have determined outcome following pharmacotherapy after acute MI in older adults. It is apparent that a number of matters require consideration in evaluation of the effectiveness of BBs. It seems that not all patients benefit equally from treatment with BBs but such an intervention reduces mortality. It is also important to recognize that the beneficial effects of BBs should not be considered in isolation since the biological system is too complex to manipulate with the use of a single class of drugs.

Effect of Exposure to Evidence‐Based Pharmacotherapy on Outcomes After Acute Myocardial Infarction in Older Adults

To assess the effect of exposure to evidence-based medication after hospital discharge for Medicare beneficiaries with acute myocardial infarction (AMI). A discrete-time hazard model was used to estimate time to outcome associated with exposure to four drug classes (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-II receptor blockers (ARBs), beta-blockers (BBs), statins, and clopidogrel) used for post-AMI secondary prevention of cardiovascular events and mortality. Medicare administrative data for a 5% random sample of beneficiaries. Medicare beneficiaries (N=9,538) hospitalized for an AMI between April 1, 2006, and December 31, 2007, who survived for at least 30days after discharge. The cohort was followed until death or December 31, 2008. Time-varying exposure was measured as proportion of days covered (PDC) for each quarter during the follow-up period. PDC was classified into five categories (0-0.2, 0.2-0.4, 0.4-0.6, 0.6-0.8, 0.8-1.0). Outcomes were mortality and a composite outcome of death or post-AMI hospitalization. Over a median follow-up of 18months, mean PDC rates ranged from 0.37 (clopidogrel) to 0.50 (statins). When comparing the highest versus lowest categories of exposure, the hazard of the composite outcome was significantly lower for all drug classes except BBs (statins, adjusted hazard ratio (aHR)=0.71, ACEIs/ARBs, aHR=0.81, clopidogrel, aHR=0.85, BBs, aHR=0.93). All four drug classes were significantly associated with reductions in mortality; the magnitude of effect for the mortality outcome was largest for statins and smallest for BBs. Age modified the effect of statins on mortality. Use of evidence-based medications for secondary prevention after AMI is suboptimal in the Medicare population, and low exposure rates are associated with significantly higher risk for subsequent hospitalization and death.

Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD

Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (-0.04 +/- 0.02 and -0.10 +/- 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 +/- 0.76% and 3.75 +/- 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5-3.5%) of measured segments (95% confidence interval) and 4.2% (2.8-5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.

To the Heart of the Matter

When cyclooxygenase (COX)-2–selective inhibitors (coxibs) first entered the market about 5 years ago, the major concern with regard to cardiovascular side effects related to their potential to increase blood pressure and cause salt and water retention, in a manner similar to conventional (nonselective) nonsteroidal antiinflammatory drugs (NSAIDs). In the short time since, wariness about these side effects has grown into widespread alarm about putative prothrombotic actions and generation of excess major cardiovascular events with these agents. See p 1024 In September 2004, safety findings of the Adenomatous Polyp Prevention on Vioxx (APPROVe) study indicated an increase in risk for myocardial infarction and stroke among subjects randomized to rofecoxib compared with those randomized to placebo. This study had been designed to examine recurrent colonic polyps rather than cardiovascular disease end points and therefore could only be considered hypothesis generating. Subsequent data from a number of observational studies further implicated the drug’s association with arterial thromboembolic disease. As with APPROVe, no single study generated sufficiently robust attestation by itself, but they provided concordant signals, and the accumulating evidence eventually reached a critical mass. As the data on rofecoxib emerged, concerns about other COX-2–selective agents on the market also grew. This was based on the assumption of a “class effect” for an increase in risk of cardiovascular disease related to preferential inhibition of prostacyclin over thromboxane and thus a tendency toward prothrombosis. The results presented by McAdam and colleagues in this issue of Circulation 1 challenge our view with regard to this prostanoid hypothesis and raise new questions about the mechanisms underlying the potential cardiovascular side effects of coxibs and traditional NSAIDs. The authors hypothesized that the enhanced systemic biosynthesis of prostacyclin in smokers was dependent on COX-2 activity. They also sought to determine the functional importance of COX2–derived prostacyclin (PGI2) in limiting platelet activation in smokers in vivo. Contrary to the conventional wisdom of an expected increase in the biosynthesis of TxA2 (related to increased platelet activation via COX-1), the authors demonstrated the opposite finding—ie, that COX-2 contributed to, and a COX-2 inhibitor reduced, TxA2 biosynthesis in smokers.

Selective Cyclooxygenase-2 Inhibitors Development in Cardiovascular Medicine

At the end of September 2004, Merck & Co announced the voluntary withdrawal of rofecoxib (Vioxx) worldwide because of an increased risk of cardiovascular events. Since its approval in 1999, Vioxx, a selective cyclooxygenase-2 (COX-2) inhibitor, has been Merck & Co’s leading drug for control of acute pain and chronic pain associated with osteoarthritis, rheumatoid arthritis, and menstruation. Last year, worldwide sales of rofecoxib reached US $2.5 billion, and it is estimated that the drug was prescribed ≈10 million times per month in the United States.1 Thus, given the number of patients involved and the serious nature of the side effects, the withdrawal raised serious concerns about the safety of other selective COX-2 inhibitors, collectively called coxibs, that are on the market and those currently under development. Celecoxib (Celebrex) and rofecoxib were the first 2 coxibs approved by the US Food and Drug Administration (FDA) and launched in 1999 by Pfizer and Merck & Co, respectively. Since then, a second generation of these drugs has emerged onto the market. Valdecoxib (Bextra) was approved by the FDA and launched in 2002. In that same year, the European regulatory authority approved 2 other coxibs: etoricoxib (Arcoxia) and parecoxib sodium (Dynastat), the prodrug of valdecoxib. Today, etoricoxib and a fifth coxib, lumiracoxib (Prexige), are under consideration for FDA approval. In view of the rapid development in this area, the main concern is whether the reported cardiovascular effects of rofecoxib are a class effect applicable to all coxibs that were initially designed to reduce the gastric toxicity of nonselective COX inhibitors. Although most of the data accumulated so far would suggest a class effect related to the general mode of action of all coxibs and the physiological role of COX-2, recent in vitro data would theoretically support the hypothesis that the cardiovascular side …