Antonio B. Fernandez

Statins and Interstitial Lung Disease: A Systematic Review of the Literature and of Food and Drug Administration Adverse Event Reports

OBJECTIVE To systematically review all published case reports and the US Food and Drug Administration adverse event reporting (FDA-AER) database to examine the relationship between statins and interstitial lung disease (ILD). DATA SOURCES PubMed (1987 to September 2007) and the FDA-AER database (as of June 2007) were searched for reports of ILD in which a statin was listed as a causative suspect. REVIEW METHODS Two authors (one author for Pub Med cases and one for FDA-AER cases) independently abstracted patient data. Given the paucity of information, all case reports and case series in English and French were included. All adverse event reports from the FDA-AER database in which a statin was listed as causative suspect were included. RESULTS The literature search using PubMed yielded eight articles describing a total of 14 case reports of ILD in association with statin use. The FDA-AER system database contained 162 cases of reported statin-induced ILD as of June 2007. For every 10,000 reports of a statin-associated adverse event, approximately 1 to 40 reports were for ILD. CONCLUSIONS Statin-induced ILD is a possible newly recognized side effect of statin therapy. The mechanism of lung injury is not defined. The current review provides novel information from the FDA-AER that supports a possible, although unusual, pulmonary class effect of statins.

Special FeaturesStatins and Interstitial Lung Disease: A Systematic Review of the Literature and of Food and Drug Administration Adverse Event Reports

OBJECTIVE To systematically review all published case reports and the US Food and Drug Administration adverse event reporting (FDA-AER) database to examine the relationship between statins and interstitial lung disease (ILD). DATA SOURCES PubMed (1987 to September 2007) and the FDA-AER database (as of June 2007) were searched for reports of ILD in which a statin was listed as a causative suspect. REVIEW METHODS Two authors (one author for Pub Med cases and one for FDA-AER cases) independently abstracted patient data. Given the paucity of information, all case reports and case series in English and French were included. All adverse event reports from the FDA-AER database in which a statin was listed as causative suspect were included. RESULTS The literature search using PubMed yielded eight articles describing a total of 14 case reports of ILD in association with statin use. The FDA-AER system database contained 162 cases of reported statin-induced ILD as of June 2007. For every 10,000 reports of a statin-associated adverse event, approximately 1 to 40 reports were for ILD. CONCLUSIONS Statin-induced ILD is a possible newly recognized side effect of statin therapy. The mechanism of lung injury is not defined. The current review provides novel information from the FDA-AER that supports a possible, although unusual, pulmonary class effect of statins.

Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

OBJECTIVE To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort. DESIGN Population-based prospective cohort study. PARTICIPANTS A diverse population sample of 6233 men and women aged 45 to 84 years without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD and CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken. MAIN OUTCOME MEASURES Incident CHD and CVD events. RESULTS Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 patients (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0% vs. 3.9%, P = 0.13 for CHD and 6.6% vs. 5.5%, P = 0.19 for CVD). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (hazard ratio 0.99; 95% confidence interval, 0.74-1.33; P = 0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events. CONCLUSIONS In persons without a history of CVD, AMD was not associated with an increased risk of CHD or CVD.

Relation of Corneal Arcus to Cardiovascular Disease (From the Framingham Heart Study Data Set)

Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD. A prospective analysis was performed using Cox proportional-hazards regression models in the Framingham Heart Study Original Cohort and Offspring Cohort database. This cohort included 23,376 patient-examinations, during 3,890 (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus was no longer predictive of either CVD or CAD, however, after adjustment for age and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and 1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus predicted CVD and CAD in the community-based Framingham Heart Study cohort because of the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CAD.

Biomarkers in Trypanosoma cruzi-Infected and Uninfected Individuals with Varying Severity of Cardiomyopathy in Santa Cruz, Bolivia

Background Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc−) individuals. Methods Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc− groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed. Results Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.

Hyperendemic Chagas Disease and the Unmet Need for Pacemakers in the Bolivian Chaco

The Southern Cone Initiative to control Chagas disease is a major public health success story [1]. Household insecticide spray programs have greatly diminished infestation by Triatoma infestans, the major domestic vector, blood bank and congenital Chagas disease screening have been implemented widely, and the estimated prevalence of Trypanosoma cruzi infection has fallen by more than 50% in the last 20 years [2]. Morbidity and mortality from Chagas cardiomyopathy, the most serious manifestation of T. cruzi infection, have declined progressively with disruption of domestic vector-borne transmission and increasing availability of advanced cardiac care [3]. The major exception to this pattern of success is the Gran Chaco, an ecological zone shared among Argentina, Bolivia, and Paraguay, and host to the highest rates of vector infestation and T. cruzi infection ever reported. Challenges include rapid reinfestation after spray campaigns, insecticide resistance, and sylvatic Tri. infestans populations [4]–[6]. Chagas cardiomyopathy occurs in an estimated 20%–30% of T. cruzi-infected individuals and features a chronic inflammatory process affecting the conduction system and myocardium [2], [7]. The earliest signs are typically bundle branch blocks and segmental wall motion abnormalities, usually beginning in early adulthood [8]. Later, patients may develop ventricular tachycardia, severe sinus bradycardia, high degree atrioventricular block (AVB), apical aneurysm, progressive dilated cardiomyopathy, and thromboemboli [2]. Syncope from heart block or severe bradycardia is common. Once conduction system abnormalities or arrhythmias are present, patients have shortened survival; signs of left ventricular dysfunction are associated with high short-term mortality [2]. Where accessible, advanced cardiac management has significantly improved the prognosis for patients with Chagas cardiomyopathy [9]. In 2011, we conducted a study of T. cruzi infection in seven villages in the Bolivian Chaco [6]. T. cruzi infection prevalence was 26.2% among residents younger than 20, 85.4% among 20–29-year-olds and 96.7% among participants 30 years or older. We then offered electrocardiograms (ECGs) to all study participants 20 years or older with T. cruzi infection. A total of 327 seropositive participants, 59% of infected study participants, had an ECG evaluated by the study cardiologists. Within a few days, we began to see patients who urgently needed pacemakers. In this article, we present a patient case report and a brief description of other patients found to need pacemakers, and we place these findings in the larger context of the Bolivian Chaco and the impact of Chagas heart disease there.

Coming of Age: Considerations in the Prescription of Exercise for Older Adults.

Older adults represent the fastest-growing age demographic of the population. Physiological changes associated with primary aging and concurrent chronic disease adversely impact functional capacity, health outcomes, and quality of life. For these reasons, there is a national emphasis for healthcare providers to improve the health, function, and quality of life of older adults to preserve independent living and psychological well-being. The benefits of regular physical activity or exercise with regard to aging and disease are indisputable, yet many clinicians do not prescribe exercise to older adults. This reluctance may be attributable to a lack of knowledge regarding appropriate exercise prescription for older adults in light of the potential risks and benefits of various doses and types of exercise. In addition, clinicians and patients may have concerns about potential health considerations relevant to older adults such as comprehensive pre-exercise screening and exercise-drug interactions. In light of this, the following review presents (1) guidelines for exercise prescription in older adults and modification of these guidelines for patients with the most common age-associated comorbidities; (2) recommendations for pre-exercise screening prior to initiating an exercise program in older adults; (3) considerations for older adults on one or more medications; and (4) common barriers to adopting and maintaining exercise in an older population. Our goal is to provide a framework that clinicians can follow when prescribing exercise in older adults while considering the unique characteristics and concerns present in this population.

Circulating Serum Markers and QRS Scar Score in Chagas Cardiomyopathy

Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.

Reduced High-density Lipoprotein Cholesterol in Patients Receiving Rosiglitazone and Fenofibrate

ATIENT 1 66-year-old woman with type 2 diabetes mellitus, dysipidemia, and coronary artery disease was treated with spirin, metoprolol, metformin, fluvastatin, rosiglitazone, nd hydrochlorothiazide. Because of hypertriglyceridemia, etformin was increased and fenofibrate was added. Her DL-C decreased from 46 mg/dL to 10 to 15 mg/dL (Figure ). On the basis of reports of decreased HDL-C with rosglitazone, her medication was switched to pioglitazone. er HDL-C increased to 47 mg/dL without other changes in ifestyle or medication.

Age-Related Macular Degeneration and Incident Stroke: A Systematic Review and Meta-Analysis.

Background Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over 65 years old in the United States and has been associated with cardiovascular risk and decreased survival. There is conflicting data, however, regarding the contribution of AMD to the prediction of stroke. Aim To determine whether AMD is a risk indicator for incident stroke in a meta-analysis of available prospective and retrospective cohort studies published in the English literature. Methods We performed a systematic literature search of all studies published in English with Pub Med and other databases from 1966 to August 2014, reporting stroke incidence in patients with macular degeneration. Two investigators independently extracted the data. A random effects model was used to report Odds ratios (OR), with corresponding 95% confidence intervals (CI). Meta-regression using a mixed linear model was used to understand potential heterogeneity amongst studies. Results We identified 9 studies that reported stroke incidence in patients with and without early AMD (N = 1,420,978). No significant association was found between early AMD with incident stroke. Combined, these 9 studies demonstrated random effects (OR, 1.12; CI, 0.86–1.47; I2 = 96%). Meta-regression on baseline covariates of age, sex, and year of publication did not significantly relate to heterogeneity. Conclusions We found no significant relationship between AMD and incident stroke. Further studies are needed to clarify other causes of decreased survival in patients with AMD.