The transient outward K+ current ( I to) in the heart is responsible for the initial phase of repolarization and for setting the plateau voltage of the ventricular action potential. Recently, Kv4.3 has emerged as the leading candidate α-subunit gene that underlies I to in larger mammals such as dogs and humans. We have cloned the human Kv4.3 homolog and describe a carboxyl-terminal splice variant that inserts 19 amino acids with a consensus protein kinase C (PKC) phosphorylation site into the protein after the last membrane-spanning segment. The coding region of Kv4.3 is comprised of at least five exons and is located on chromosome 1p13.3. In the basal state the basic biophysical properties of both of the splice variants are identical.

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The majority of breast cancers are diagnosed in postmenopausal women. Competing comorbidities, particularly cardiovascular disease (CVD), should be considered when individualizing adjuvant therapies for these women. We compared the 10-year predicted breast cancer recurrence risk with CVD risk among postmenopausal women with hormone receptor-positive (HR+), non-metastatic breast cancer. CVD risk factor data were prospectively collected from postmenopausal women with stage I-III, HR+ breast cancer initiating adjuvant aromatase inhibitor therapy. We compared predicted 10-year CVD risk, including the composite index heart age, computed from modified Framingham risk score, with predicted 10-year risk of breast cancer recurrence using Adjuvant! Online. We created multivariable logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (CI) for greater CVD risk than breast cancer recurrence risk. Among 415 women, mean age and heart age were 60 and 67 years, respectively. Overall, 43% of women had a predicted 10-year CVD risk equivalent to breast cancer recurrence risk and 37% had CVD risk higher than breast cancer recurrence risk. Predicted CVD risk was higher than breast cancer recurrence risk for stage I disease (OR: 6.1, 95% CI: 3.4–11.2) or heart age >65 (OR: 12.4, 95% CI: 7.0–22.6). The majority of postmenopausal women with HR+ early breast cancer had a predicted 10-year CVD risk that was equivalent to or higher than breast cancer recurrence risk. Physicians should weigh competing risks and offer early screening and cardiac prevention strategies for women at a greater risk for CVD.

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Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. Fortunately, it is often preventable with early adoption of lifestyle modification, prevention of risk factor onset, and aggressive treatment of existing risk factors. The Million Hearts Initiative is an effort by the Centers for Disease Control that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years. As part of this initiative, we present a simply organized ''ABCDE'' approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. ABCDE stands for assessment of risk, antiplatelet therapy, blood pressure management, cholesterol management, cigarette/tobacco cessation, diet and weight management, diabetes prevention and treatment, and exercise, interventions regularly used to reduce cardiovascular (CV) risk. Throughout this article we summarize recommendations related to each topic and reference landmark trials and data that support our approach. We believe that the ABCDE approach will be the core framework for addressing CV risk in our effort to prevent CVD. IntroductionAtherosclerotic cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Fortunately, it is a condition ideally suited for prevention. CVD accounts for more than 2 million heart attacks and strokes in this country alone. It is also caused by risk factors that are readily modified by lifestyle change and inexpensive pharmacotherapy. As identified in the INTERHEART study (A Global Case-Control Study of Risk Factors for Acute Myocardial Infarction), 9 risk factors-smoking, dyslipidemia, diabetes mellitus (DM), hypertension, abdominal obesity, stress, poor diet, physical inactivity, and excess alcohol consumption-were associated with more than 90% of the risk for a first myocardial infarction (MI). 1 Finally, it takes decades to develop. In the wake of an MI or stroke, patients and clinicians alike often lament the presence of longstanding risk factors that may have been overlooked.