Elizabeth V Ratchford

mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion

Background We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. Methods and Results mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the interventions 2 core components. After establishing baseline activity during a blinded run‐in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone‐delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician‐written, theory‐based algorithm using real‐time activity data and 16 personal factors with a 10 000 steps/day goal. Forty‐eight outpatients (46% women, 21% nonwhite) enrolled with a mean±SD age of 58±8 years, body mass index of 31±6 kg/m2, and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], −580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). Conclusions An automated tracking‐texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. Clinical Trial Registration URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812.

Usefulness of Coronary and Carotid Imaging Rather than Traditional Atherosclerotic Risk Factors to Identify Firefighters at Increased Risk for Cardiovascular Disease

Cardiovascular disease (CVD) accounts for 45% of deaths in on-duty firefighters, in contrast to 15% of all deaths occurring on conventional jobs. Therefore, with the goal of developing a tailored prevention program, we assessed CVD risk in a cohort of 50 firefighters using imaging and traditional risk factors. Participants were aged ≥40 years without a history of CVD or diabetes. CVD risk was assessed by way of history, physical examination, blood tests, risk scores, coronary artery calcium (CAC), and carotid intima-media thickness (cIMT). Median age was 46xa0years; 90% of subjects were men, 92% were white, and 30% were former smokers. Only 4% of subjects were hypertensive but 48% were prehypertensive. Only 14% of subjects had a normal body mass index; 38% were overweight, 48% were obese, and 46% had a high waist circumference. Based on fasting glucose ≥100xa0mg/dl or hemoglobin A1c ≥5.6%, 50% of subjects had prediabetes and 2% had diabetes. Median total cholesterol was 196xa0mg/dl; median high-sensitivity C-reactive protein was 1.0xa0mg/L. CAC was detected in 22% of subjects and carotid plaque was detected in 36%. Using standard reference databases, 54% of subjects had cIMT greater than the seventy-fifth percentile; 66% had carotid plaque and/or cIMT greater than the seventy-fifth percentile. Atherogenic lipoprotein markers and risk scores did not differ between firefighters who had subclinical atherosclerosis and those who did not. Traditional CVD risk assessment does not adequately identify at-risk firefighters. In contrast, CAC and cIMT were useful for identifying increased risk and implementing primary prevention. In conclusion, early detection and integration of imaging with traditional risk assessment will be important in preventing premature death and disability among firefighters.

Diagnosis and treatment of uncomplicated type B aortic dissection

A type B dissection involves the aorta distal to the subclavian artery, and accounts for 25–40% of aortic dissections. Approximately 75% of these are uncomplicated with no malperfusion or ischemia. Multiple consensus statements recommend thoracic endovascular aortic repair (TEVAR) as the treatment of choice for acute complicated type B aortic dissections, while uncomplicated type B dissections are traditionally treated with medical management alone, including strict blood pressure control, as open repairs have a prohibitively high morbidity of up to 31%. However, with medical treatment alone, the morbidity, including aneurysm degeneration of the affected segment, is 30%, and mortality is 10% over 5 years. For both chronic and acute uncomplicated type B aortic dissections, emerging evidence supports the use of both best medical therapy and TEVAR. This paper reviews the current diagnosis and treatment of uncomplicated type B aortic dissections.

Medical management of claudication

&NA; Peripheral artery disease (PAD) is common and associated with significant morbidity and mortality. Optimal medical management of PAD is required for each patient, irrespective of the decision regarding lower extremity revascularization. The goals include reducing cardiovascular morbidity and mortality and improving quality of life. The approach should consist of aggressive and individualized risk factor modification including smoking cessation, antiplatelet therapy, a statin, and an angiotensin‐converting enzyme inhibitor. Exercise is critical for cardiovascular health and highly effective for improving claudication symptoms. Cilostazol may be considered for symptomatic treatment in certain patients.

Impact of the modified Atkins diet on cardiovascular health in adults with epilepsy

AIMnThe current study investigated biochemical and vascular markers of cardiovascular health in adult patients with epilepsy treated with long-term (greater than 1year) ketogenic diet therapy compared with controls.nnnMETHODnAnthropometric measures, serum fasting lipid panel, apolipoproteins A-1 and B, lipoprotein sub-fractions as well as common carotid intima-media thickness (cIMT), and plaque presence were assessed in 20 adult patients with epilepsy on a modified Atkins diet (MAD) for >1year started as an adult compared with 21 adult patients with epilepsy naïve to diet therapy.nnnRESULTSnPatients treated with MAD had significantly lower weight, body mass index, waist and hip circumference, percent body fat, and serum triglyceride levels when compared with control patients. In contrast, they had significantly higher serum levels of small low-density-lipoprotein (LDL) particles and were significantly more likely to have LDL pattern B in which small LDL particles predominate when compared with controls. However, there was no significant difference in cIMT or plaque presence between groups.nnnCONCLUSIONnOur results provide clinical evidence demonstrating the cardiovascular safety of a high-fat, low-carbohydrate diet used in adults with epilepsy for at least 12months. It also highlights potential markers of cardiovascular risk - small dense LDL particles - that should be closely monitored in adults treated with diet therapy long-term.

Approach to Lower Extremity Edema

Opinion statementLower extremity edema is extremely common among patients seen across multiple specialties. The differential diagnosis is broad and ranges from simple dependent edema to more complex conditions such as chronic venous disease and lymphedema. Several key features from the history and physical exam can assist with the diagnosis. Imaging is rarely necessary at the initial visit unless venous thromboembolism is suspected. Treatment is specific to the etiology of the edema, but compression stockings, elevation, exercise, and weight loss remain the cornerstone in most cases.

Raynaud’s phenomenon

What is Raynaud’s phenomenon? Raynaud’s phenomenon is a condition that affects your blood vessels. If you have Raynaud’s phenomenon, you have periods of time called “attacks” when your body does not send enough blood to the hands and feet. Attacks usually happen when you are cold or feeling stressed. During an attack, your fingers and toes may feel very cold or numb. Raynaud’s phenomenon is also called Raynaud’s disease or Raynaud’s syndrome.

Vascular Disease Patient Information Page: The post-thrombotic syndrome.

The post-thrombotic syndrome is a condition that sometimes occurs after deep vein thrombosis (DVT) of the leg, or, less commonly, of the arm. Veins are the blood vessels that return blood from the arms, legs, and organs to the heart. In DVT, blood clots form in the veins, often leading to pain, swelling, and redness of the affected limb. These symptoms usually subside, but some patients may go on to develop chronic pain, swelling, and skin changes in the affected leg; this is known as the post-thrombotic syndrome, or PTS. In PTS, symptoms may come and go, and in some patients symptoms may be made worse by prolonged sitting, standing, and sometimes by walking. Much is unknown about PTS, but it is thought to occur when blood clots damage the valves of the veins, or when persistent blood clots block the flow of blood in the veins. Valves are small flaps of tissue that help keep blood flowing in only one direction. When they are damaged, blood can flow backward (called reflux), leading to swelling and chronic skin changes such as skin darkening (hyperpigmentation), hardening (induration), and, in severe cases, poorly healing sores (ulcers). Similarly, persistent blockage of the vein can cause these problems.

Vascular Disease Patient Information Page: Peripheral artery disease

Peripheral artery disease (PAD) is narrowing of the arteries, which are the blood vessels that carry oxygen-rich blood away from the heart to the body. The narrowing is usually caused by atherosclerotic plaque. Atherosclerosis, or hardening of the arteries, affects arteries throughout the body. The symptoms depend on which part of the body is involved. When the leg arteries are blocked, the condition is called PAD.

Shedding New Light on the Magnitude of Thrombosis Risk in Patients With Myeloproliferative Neoplasms

Myeloproliferative diseases were first described by William Dameshek in 1951. In 2008, the World Health Organization established a new classification system and introduced the term myeloproliferative neoplasms (MPNs). Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are the most prevalent MPNs and are characterized by overproduction of leukocytes, erythrocytes, or platelets; development of bone marrow fibrosis; leukemic transformation; and arterial and venous thrombosis. When Dameshek proposed the term myeloproliferative diseases, he also proposed the presence of a then-undiscovered stimulus that drove proliferation. We now understand that mutation of the JAK2 gene, JAK2 V617F, is the most common stimulus, occurring in 95% of patients with PV and 60% of those with ET or PMF. Myeloproliferative neoplasms are relatively rare; are acquired in middle to older age; and are, despite their classification as neoplasms, indolent diseases, with survival measured in decades (1). Yet, MPNs exhibit marked variability in disease presentation and outcomes, especially with regard to thrombotic events. In this issue, Hultcrantz and colleagues report a study that examined thrombosis patterns in 9429 Swedish patients with MPNs diagnosed between 1987 and 2009 compared with 35820 matched control participants (2). As in prior studies, both arterial and venous thrombotic events were increased in patients with MPNs, with the highest risk around the time of MPN diagnosis, although risk persisted throughout patients lifetimes. Older age and male sex increased cumulative risk for both arterial and venous events in patients with MPNs compared with the general population, but thrombotic risk was higher in the MPN group regardless of age or sex. Of note, the highest hazard ratio that Hultcrantz and colleagues observed was for venous events in the youngest age group. The most notable contribution of this large cohort study is quantification of the magnitude of thrombotic risk that MPNs confer. To put these findings into clinical context, the hazard ratios for arterial events were similar to those for cigarette smoking, and the hazard ratios for venous events were similar to those for factor V Leiden heterozygosity. Approximately 10% of patients with MPNs had a thrombotic event within 30 days before or after diagnosis. Patients and clinicians should be keenly aware of this particularly risky period, during which risk for thrombosis is similar to that in the month after a transient ischemic attack. Unfortunately, the study did not include genomics data, but other studies enable us to speculate on the potential mechanisms responsible for the excess of arterial and venous thrombosis. Discovered in 2005, JAK2 V617F is an acquired mutation of a hematopoietic stem cell that provides a proliferative advantage and drives MPN phenotypes. Not long after its discovery in the MPN population, 2 large general population studies from Denmark (the Copenhagen City Heart Study [n= 10507] and the Copenhagen General Population study [n= 49488]) had similar findings: JAK2 V617F mutations are detected (at low clonal burden levels) in 0.1% to 0.2% of the general population (3). A more recent analysis of the 23andMe customer base (n= 252637) found similar age-dependent rates of JAK2 V617F in asymptomatic populations (4). Of note, despite the absence of overt MPN, JAK2 V617F carriers had higher rates of thrombotic events than control participants. A thrombosis signal associated with somatic mutations in blood cells was also shown in a previous study (5), in which many genes mutated in clonal hematopoietic malignancies were examined simultaneously in a large general population. Mutations were rare in persons younger than 50 years but were identified in almost 6% of those older than 65 years. JAK2 V617F was among the most common mutated genes, which also included DNMT3A, ASXL1, TET2, and PPMD1. It is important to note that in addition to an increased risk for blood disease or cancer, persons with mutations had higher rates of cardiovascular events (5). Collectively, these studies suggest that, rather than elevated blood counts driving thrombosis in MPN, confounding factors may drive risk for developing both mutations and thromboses. Arterial and venous thromboses share risk factors, including smoking, elevated body mass index, older age, and chronic inflammatory states. JAK2 V617F is uniquely connected to inflammatory pathways, both proximally and distallyinflammatory states may predispose persons to acquisition of JAK2 V617F, and JAK2 V617F signaling also drives inflammatory pathways. Persons with JAK2 V617Fpositive MPN have elevated inflammatory cytokines, which are a substantial component of disease burden. Inflammation also seems to play a role in clonal expansion of JAK2 V617F cells, further driving disease expansion (6). Inflammation is a recognized risk factor for thrombosis in the general population and is well-known to play a significant role in atherogenesis, which could enable identification of new therapeutic targets. For example, rosuvastatin reduced cardiovascular events in asymptomatic persons with normal cholesterol levels but elevated high-sensitivity C-reactive protein (hs-CRP) levels (7). More recently, targeting interleukin-1 with a monoclonal antibody reduced cardiovascular events among patients with previous myocardial infarction and elevated hs-CRP levels (8). Traditional therapeutic approaches have focused on antiplatelet agents for arterial events and anticoagulants for venous events. However, the combination of aspirin and low-dose rivaroxaban was recently shown to reduce cardiovascular events in patients with stable cardiovascular disease (9). These studies from the general population should inform future research on strategies to reduce thrombotic risk in patients with MPNs, which will also need to take into account genomics, given that treatment effects may differ by mutation. Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk that MPNs bring to affected patients. Their study shows us that the traditional approach to assessing thrombotic risk in patients with MPNs (age 60 years, prior thrombotic event, and presence of traditional cardiovascular risk factors) lacks precision and personalization. In particular, such an approach does not adequately recognize the risks that younger patients bear (10). The study of JAK2 V617F and its association with inflammation, clonal hematopoiesis, and thrombosis has shed light not only on mechanisms of thrombosis in MPNs but also on mechanisms and risks that are generalizable to the population at large. A personalized, precision medicine approach to primary and secondary thrombosis prevention for patients with MPNs should incorporate genomics, cardiovascular risk assessment, inflammatory biomarkers, and this new appreciation of the magnitude and cumulative nature of excess risk. Care of patients with MPNs should include aggressive treatment of traditional risk factors to reduce risk for arterial and venous thrombosis, regardless of age; adoption of dietary and lifestyle habits that reduce inflammation; and consideration of combined anticoagulant, antiplatelet, and anti-inflammatory treatment strategies.