Cardiovascular disease is the leading cause of death worldwide, affecting not only high-income but also low- and middle-income countries. Nearly 80 percent of all estimated cardiovascular disease–related deaths worldwide now occur in low- and middle-income countries, where nearly 30 percent of all deaths are attributable to cardiovascular disease. The health burden of cardiovascular disease and other chronic diseases is also accompanied by a significant deleterious economic impact at the level of both national economies and households. The global trends in the health and economic burden of cardiovascular disease provide a compelling argument in support of prioritizing urgent yet carefully planned efforts to prevent and control cardiovascular disease worldwide—and especially in low- and middle-income countries. After decades of escalating efforts to draw attention to the high burden of cardiovascular disease and other chronic diseases, this critically important issue is now emerging as a more central part of the global health and development agenda. The breadth of behavioral, biological, social, environmental, and systems-level factors that contribute to cardiovascular disease necessitates multisectoral approaches across the lifecourse that promote healthful lifestyles, reduce risk, and reduce cardiovascular-disease morbidity and mortality through the delivery of quality health care services. Given that the complex interactions among the determinants of cardiovascular disease vary in different contexts, real progress in control efforts will come through approaches that are driven by a country's disease burden and risk profile, capacities, resources, and priorities—approaches that are led by a country's key decision-makers and stakeholders, including governments, civil society, the private sector, and communities. Many countries are already establishing efforts to address chronic diseases. In addition to these locally driven efforts, success will require active engagement and sustained action from a wide array of stakeholders operating at global and regional levels. Mt Sinai J Med 79:632–640, 2012. © 2012 Mount Sinai School of Medicine
Atherosclerotic vascular disease not only remains the leading cause of death in the Western countries, but it has become the most common cause of morbidity and mortality in the low- and middle-income countries as well. Therefore, better understanding of the pathogenesis of atherosclerotic disease and its prevention are of fundamental importance. It is well known that it affects sequentially the aorta followed by coronary, carotid, peripheral, and intracerebral arteries, with some individual variability. The mechanisms of progression are similar in each of the beds, with increasing lipid accumulation in the arterial wall along with macrophages and T-cell infiltration, paucity of smooth-muscle cell proliferation and collagen deposition, and endothelial-cell dysfunction and hypercoagulability playing an important role at the time of acute manifestations of the disease. Fundamental to this inflammatory process is the presence of classic risk factors, regardless of the involved territory. Therefore, the concept of palliative treatment must be reserved for only those who have progressed beyond preventive measures. Mt Sinai J Med 79:641–653, 2012. © 2012 Mount Sinai School of Medicine
Atherosclerosis is the leading cause of death and disabling disease. Whereas risk factors are well known and constitute therapeutic targets, they are not useful for prediction of risk of future myocardial infarction, stroke, or death. Therefore, methods to identify atherosclerosis itself have been tested and found useful (ie, coronary calcium detection by computed tomography scanning, reduction in ankle-brachial index, and ultrasound scanning of the carotid arteries). This review will focus on the latter technique. Detection of thickened carotid intima-media by ultrasound has been used in many large epidemiological studies, but although it has been found to be associated with increased risk of cardiovascular death, its clinical utility is limited. Detection of carotid plaque has, on the other hand, been found to be associated with a substantial risk of future events. Similarly, detection of plaque in the femoral arteries is associated with increased risk, and plaque in the femoral as well as carotid arteries predicts even higher risk. Furthermore, quantification of plaque size (plaque area), such as quantification of amount of coronary calcium on computed tomography scanning, improves predictability—the larger the plaques, the higher the risk. So far, studies using ultrasound all have been performed with 2-dimensional ultrasound imaging. Recently, 3-dimensional ultrasound imaging has been introduced, which allows for more accurate quantification of atherosclerosis. Small studies pioneering its use have indicated the utility of measuring changes in vessel-wall volume and plaque volume with respect to treatment effect. The High-Risk Plaque Initiative BioImage Study is currently investigating the predictive value of total carotid plaque volume with respect to prediction of future cardiovascular events. Mt Sinai J Med 79:654–663, 2012. © 2012 Mount Sinai School of Medicine
The involvement of vascular factors in Alzheimer dementia was first appreciated over 100 years ago. Recently, significant advances in our understanding of these brain-vascular relationships have taken place. Vascular cognitive impairment is now recognized as a distinct group of interrelated vascular-based neurological insults that can accumulate and lead to dementia. Importantly, the pathology of vascular cognitive impairment extends far beyond brain destruction wrought by major stroke. Other subtle changes may also arise that contribute to vascular cognitive impairment and dementia, including subclinical stroke, white-matter changes such as hyperintensities and lipohyalinosis, small lacunar infarcts, cerebral hypoperfusion, and compromise of the blood-brain barrier. In this review we critically examine the emerging body of evidence that relates atherosclerotic risk factors, brain functioning, and Alzheimer disease. Mt Sinai J Med 79:664–673, 2012. © 2012 Mount Sinai School of Medicine
There is an important correlation between vascular risk factors and nonspecific imaging findings in the brain such as white-matter hyperintensities. These vascular risk factors are also associated with dementia and lesser forms of cognitive impairment. One hypothesis is that these vascular risk factors lead to disruption of connective networks in the central nervous system that are supported by myelinated white-matter fibers, which in turn lead to deficits in functional signaling between various brain regions. Another possibility is an alteration of the neurovascular coupling due to vascular risk factors. This reduced functional signaling contributes to the cognitive deficits in persons harboring these vascular risk factors. Lifestyle changes may restore some of these functional deficits through brain plasticity. It is imperative that preclinical diagnostic techniques are developed to identify these early brain changes in persons harboring vascular risk factors, as such efforts may improve primary and secondary prevention efforts. Recently developed imaging techniques may provide objective imaging biomarkers to measure the structural and functional brain changes in persons with vascular risk factors and resulting subclinical atherosclerotic disease. This article reviews a few of these novel imaging techniques. Mt Sinai J Med 79:674–682, 2012. © 2012 Mount Sinai School of Medicine
Cardiovascular-disease prevention is often inadequate due to several factors. Lack of professional adherence to guidelines, unaffordable medication, and lack of patients' adherence to treatment are the most important. It has been suggested that an affordable, fixed-dose combination drug containing evidence-based active compounds could improve cardiovascular prevention by improving patients' adherence to treatment. The available evidence suggests that the polypill strategy can achieve this objective and it will gain a place in the therapeutic armamentarium for the prevention of cardiovascular events in patients at high risk. Mt Sinai J Med 79:683–688, 2012. © 2012 Mount Sinai School of Medicine
The rate of acute complications of atherosclerosis (acute myocardial infarction, ischemic stroke) has continuously decreased over the last 20 years in Western countries. This is largely explained by improvements in the reduction and treatment of cardiovascular risk factors and by the increasing number of patients who benefit from preventive treatments such as antiplatelet, lipid-lowering, or antihypertensive drugs. This means also that, when testing new drugs aimed at either halting or even reversing the progression of atherosclerotic plaques, a large number of patients will need to be included in clinical trials to demonstrate an improvement in patient outcome with the drugs. Pharmaceutical companies are therefore looking for early surrogate markers that could be evaluated in a small number of patients to predict the beneficial effects of new drugs on atherosclerotic plaques before moving to costly clinical trials with a large number of patients. In this review, we will discuss the place of atherosclerotic plaque imaging with magnetic resonance imaging and positron emission tomography for the evaluation of new antiatherosclerotic drugs. Mt Sinai J Med 79:689–704, 2012. © 2012 Mount Sinai School of Medicine
Nonvalvular atrial fibrillation increases in prevalence with age and often requires long-term oral anticoagulation to prevent ischemic stroke. Vitamin K antagonists are highly effective for stroke prevention. However, suboptimal risk assessment, variability in response, drug and food interactions, and monitoring requirements result in underprescription of warfarin by physicians and poor adherence to therapy by patients. In addition, the vitamin K antagonists modulate coagulation by inhibiting multiple coagulation factors (factors II, VII, IX, and X). New oral direct factor IIa and Xa inhibitors offer improved risk-benefit profiles, simplifying thromboprophylaxis and overcoming some practical barriers to long-term therapy. Their potential benefit is a function of targeting specific activated factors produced at key junctions of the coagulation system. However, important questions about patient management with these new agents have not been fully answered by studies completed to date and clinical inertia must yet be overcome. Mt Sinai J Med 79:705–720, 2012. © 2012 Mount Sinai School of Medicine
Traditional risk factors explain most of the risk associated with coronary heart disease, and after adjustment for risk factors family history was believed to contribute very little to population-attributable risk of coronary heart disease. However, the INTERHEART study demonstrated an independent association of family history of coronary heart disease with acute myocardial infarction. To assess this relationship more comprehensively in multiple datasets in different populations, we carried out a detailed review of the available evidence. Case-control studies involving 17,202 cases and 30,088 controls yielded a pooled unadjusted odds ratio (random-effects model, overall I2 = 64.6%, P = 0.000) of 2.03 (95% confidence interval: 1.79–2.30), whereas cohort studies that included 313,837 individuals yielded an unadjusted relative risk for future coronary heart disease (random-effects model, overall I2 = 88.7%, P = 0.000) of 1.60 (95% confidence interval: 1.44–1.77). Although the presence of family history of coronary heart disease indicates a cumulative exposure of shared genes and environment, the risk estimates for family history did not attenuate significantly after adjustment for conventional coronary heart disease risk factors in several studies. It is probably an oversimplification to dichotomize the family history variable into a simple “yes” or “no” risk factor, as the significance of family history is influenced by several variables, such as age, sex, number of relatives, and age at onset of disease in the relatives. Moreover, a quantitative risk-assessment model for the family history variable, such as the “family risk score,” has a positive linear relationship with coronary heart disease. More studies are warranted to assess the benefits and risks of intensive interventions, both targeted individually and at the family level, among individuals with a valid family history and borderline elevated risk factors. Mt Sinai J Med 79:721–732, 2012. © 2012 Mount Sinai School of Medicine
Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. Mt Sinai J Med 79:733–748, 2012. © 2012 Mount Sinai School of Medicine
Background: AA amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils derived from the acute-phase reactant serum amyloid A protein. It is typically a consequence of chronic inflammatory conditions like rheumatoid arthritis or Crohn's disease, although more patients are being identified who have more unusual causes or no known inflammatory stimulus.
Methods: We performed a retrospective chart review of all patients with AA amyloidosis seen at Mount Sinai during the period of 1997–2012. Particular attention was paid to the patients' underlying diseases, extent of organ involvement, levels of inflammatory markers and proinflammatory cytokines, presence of pyrin gene mutations, and outcomes.
Results: Forty-three patients were seen at Mount Sinai with AA amyloidosis during this period. The most common underlying diseases were rheumatoid arthritis (21%) and Crohn's disease (16%), though 21% of patients were considered to have idiopathic AA amyloid after an extensive search found no underlying inflammatory disease. Almost all patients (95%) had renal involvement based on biopsy or clinical criteria, with 19 patients (44%) eventually requiring dialysis and 5 (12%) undergoing renal transplantation. Inflammatory markers were elevated in most patients; however, interleukin-6 was the only consistently elevated cytokine. Three patients (of 9 tested) were found to be positive for the E148Q pyrin gene mutation.
Conclusions: Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin-6, in comparison with other cytokines, could represent a therapeutic target. Mt Sinai J Med 79:749–756, 2012. © 2012 Mount Sinai School of Medicine
The potential benefits of the electronic health record over traditional paper are many, including cost containment, reductions in errors, and improved compliance by utilizing real-time data. The highest functional level of the electronic health record (EHR) is clinical decision support (CDS) and process automation, which are expected to enhance patient health and healthcare. The authors provide an overview of the progress in using patient data more efficiently and effectively through clinical decision support to improve health care delivery, how decision support impacts anesthesia practice, and how some are leading the way using these systems to solve need-specific issues. Clinical decision support uses passive or active decision support to modify clinician behavior through recommendations of specific actions. Recommendations may reduce medication errors, which would result in considerable savings by avoiding adverse drug events. In selected studies, clinical decision support has been shown to decrease the time to follow-up actions, and prediction has proved useful in forecasting patient outcomes, avoiding costs, and correctly prompting treatment plan modifications by clinicians before engaging in decision-making. Clinical documentation accuracy and completeness is improved by an electronic health record and greater relevance of care data is delivered. Clinical decision support may increase clinician adherence to clinical guidelines, but educational workshops may be equally effective. Unintentional consequences of clinical decision support, such as alert desensitization, can decrease the effectiveness of a system. Current anesthesia clinical decision support use includes antibiotic administration timing, improved documentation, more timely billing, and postoperative nausea and vomiting prophylaxis. Electronic health record implementation offers data-mining opportunities to improve operational, financial, and clinical processes. Using electronic health record data in real-time for decision support and process automation has the potential to both reduce costs and improve the quality of patient care. Mt Sinai J Med 79:757–768, 2012. © 2012 Mount Sinai School of Medicine
This article reviews a selection of undergraduate programs intended to increase successful minority participation in science, technology, engineering, and mathematics majors, potentially leading to biomedical careers. The object is to examine their structure, consider how well they address the issues of the target population, and assess the extent to which they have met/meet their goals. As a means of conducting this review, the first step is to examine the concepts used as the building blocks for program design. These concepts are found in a shared, yet often undefined, vocabulary used in most undergraduate programs for minority students. The hypothesis is that a shared vocabulary obscures a broad range of meaning and interpretation that has serious ramifications affecting student success. How these building blocks are understood and implemented strongly reflects the institution where the program is housed. The discussion further considers the nature of a number of programs created by the National Science Foundation and the National Institutes of Health specifically for underrepresented minority students and examines one program in detail, the University of California Berkeley's National Science Foundation Research Experience for Undergraduates Program in Molecular, Cell, and Evolutionary Biology. The characteristics of federally organized programs and the Research Experience for Undergraduates are contrasted with 2 very successful student-centered local programs based on a different conceptual model. Mt Sinai J Med 79:769–781, 2012. © 2012 Mount Sinai School of Medicine