Esther S.H. Kim

Status of Women in Cardiovascular Clinical Trials

Cardiovascular disease (CVD) is the most common cause of death in American women and accounts for a full one-third of all deaths.1 Although the common perception may be that CVD affects mainly men, there is equal prevalence of this disease between the genders by the age of 40, and by the age of 60 more women than men are affected. More women than men have died from CVD causes on a yearly basis since the mid 1980s, and whereas the CVD mortality has steadily declined in men over the past 30 years, it has remained steady in women until very recently when CVD mortality was noted to decrease for both genders.2 See accompanying article on page 277 The impact of cardiovascular disease (CVD) on the health status of American women is gaining more recognition and has become the focus of public education efforts such as the “Go Red for Women” campaign sponsored by the American Heart Association and the “Red Dress” project sponsored by the Department of Health and Human Services, the National Institutes of Health (NIH), and the National Heart Lung and Blood Institute (NHLBI). These programs are, in part, a response to the increasing awareness of cardiovascular disease as a major source of morbidity and mortality in U.S. women. The importance of CVD as a major source of mortality in women was recognized early on by federally funded institutes including the Public Health Service Task Force, which brought attention to concerns about the health information available to women and the historical lack of research focus on women’s health in its 1985 Report of the Public Health Service Task Force on Women’s Health Issues .3 In response to this report, the National Institutes of Health adopted a policy for the inclusion of women in clinical research …

Enrollment of Women in National Heart, Lung, and Blood Institute-Funded Cardiovascular Randomized Controlled Trials Fails to Meet Current Federal Mandates for Inclusion

To the Editor: In 1986, the National Institutes of Health (NIH) established a policy for the inclusion of women in clinical research that was subsequently enacted into public law when Congress approved the NIH Revitalization Act of 1993 ([1][1]). This Act states that women and minorities must be

Using the ankle-brachial index to diagnose peripheral artery disease and assess cardiovascular risk.

The ankle-brachial index is valuable for screening for peripheral artery disease in patients at risk and for diagnosing the disease in patients who present with lowerextremity symptoms that suggest it. The ankle-brachial index also predicts the risk of cardiovascular events, cerebrovascular events, and even death from any cause. Few other tests provide as much diagnostic accuracy and prognostic information at such low cost and risk. The authors seek to convince you to measure the ankle-brachial index in any patient you suspect may have peripheral artery disease, whether or not they have symptoms.

Clinical Manifestations of Fibromuscular Dysplasia Vary by Patient Sex: A Report of the United States Registry for Fibromuscular Dysplasia

To the Editor: Fibromuscular dysplasia (FMD) is an uncommon arteriopathy which can result in stenosis, aneurysm, dissection, and/or occlusion of arteries. It most commonly affects the renal, extracranial carotid, and vertebral arteries but can affect any artery. Although FMD occurs primarily in

Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia.

Patients with fibromuscular dysplasia (FMD) may have clinical features consistent with Mendelian vascular connective tissue disorders. The yield of genetic testing for these disorders among patients with FMD has not been determined. A total of 216 consecutive patients with FMD were identified. Clinical characteristics were collected and genetic test results reviewed for abnormalities in the following genes: transforming growth factor-β receptor 1 and 2 (TGFβR1 and TGFβR2), collagen 3A1, fibrillin-1, smooth muscle α-actin 2, and SMAD3. A total of 63 patients (63/216; 29.2%) were referred for genetic counseling with testing performed in 35 (35/63; 55.6%). The percentage of patients with a history of arterial or aortic dissection, history of aortic aneurysm, systemic features of a connective tissue disorder, and a family history of sudden death was significantly larger in the group that underwent genetic testing (62.9% vs 18.2%, p < 0.001; 8.6% vs 1.7%, p = 0.02; 51.4% vs 17.1%, p < 0.001; and 42.9% vs 22.7%, p = 0.04, respectively). Two patients were found to have distinct variants in the TGFβR1 gene (c.611 C>T, p.Thr204lle and c.1285 T>C, p.Tyr429His). The yield of genetic testing for vascular connective tissue disorders was low in a high-risk subset of FMD patients. However, two patients with a similar phenotype had novel and distinct variants in the TGFβR1 gene, a finding which merits further investigation.

Relationship Between Metabolic Syndrome and Carotid Intima-Media Thickness: Cross-Sectional Comparison Between Psoriasis and Psoriatic Arthritis

To determine the differences in carotid intima‐media thickness (CIMT) between patients with psoriatic diseases with and without metabolic syndrome.

International Participation in Cardiovascular Randomized Controlled Trials Sponsored by the National Heart, Lung, and Blood Institute

OBJECTIVES The aim of this study was to describe international enrollment and participation in National Institutes of Health (NIH)-sponsored cardiovascular randomized controlled trials (RCTs). BACKGROUND RCTs provide the evidence base for major societal guidelines and profoundly influence patient care in the United States. Increased international involvement in clinical trials has been observed, but the rate of international enrollment in NIH-sponsored cardiovascular RCTs has not been described. METHODS The NIH registry of clinical trials was searched for phase III or IV cardiovascular RCTs funded by the National Heart, Lung, and Blood Institute. Studies with outcomes of myocardial infarction, stroke, or death published between 1997 and 2009 were included. Rates of international enrollment were obtained from published data or personal communication with corresponding authors. RESULTS Twenty-four studies met all inclusion criteria. Nineteen trials including 151,682 patients had international participation (IP), with median IP of 9.5% (range 0% to 100%). Coronary artery disease trials (11 studies) had nearly 50% international enrollment. High-risk trials and trials testing acute interventions tended to have higher rates of IP. CONCLUSIONS Cardiovascular RCTs sponsored by the National Heart, Lung, and Blood Institute have substantial rates of international enrollment, particularly coronary artery disease trials. Given questions of applicability and ethical and financial considerations, IP in U.S. clinical trials deserves further scrutiny.

Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.

Epidemiology of fibromuscular dysplasia: A review of the literature:

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory disease of medium sized arteries that has been described in multiple anatomic territories with a wide variety of manifestations (e.g. beading, stenosis, occlusion, aneurysm, or dissection). While the first case of FMD is thought to have been described over 75 years ago, the causes, natural history, and epidemiology of FMD in the general population remain incompletely understood. This article reviews important historical and contemporary contributions to the FMD literature that inform our current understanding of the prevalence and epidemiology of this important disorder. A particular focus is given to studies which form the basis for FMD prevalence estimates. Prevalence estimates for renal FMD are derived from renal transplant donor studies and sub-studies of clinical trials of renal artery stenting; however, it is unclear how well these estimates generalize to the overall population as a whole. Newer data are emerging examining the genetic associations and environmental interactions with FMD. Significant contributions to the understanding of FMD have come from the United States Registry for Fibromuscular Dysplasia; however, many unanswered questions remain, and future studies are required to further characterize FMD epidemiology in general populations and advance our understanding of this important disorder.

External validation of the HIT Expert Probability (HEP) score

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.