Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine
- Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES)
- Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy: 20-Year Follow-Up of West of Scotland Coronary Prevention Study
- Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction
- Endothelial p110γPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury
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Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine
Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. To improve the prognosis of patients who have type 1 diabetes mellitus, first, accurate CVD risk prediction is crucial to initiate targeted primary prevention. In this study, we provide a risk model for composite CVD outcome: ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease. These are the 4 most serious CVD events associated with premature death and reduced quality of life among patients with type 1 diabetes mellitus. Although the underlying pathophysiology for these 4 events may be different, they share the same risk factors and the strategies for primary prevention are similar, eg, promoting a healthy lifestyle and treating hypertension and dyslipidemia. This high-performing CVD risk model allows the implementation of decision rules in a clinical setting, thereby potentially improving the treatment and prognosis of patients with type 1 diabetes mellitus. Second, the CVD risk model allows the development of a risk calculator for use in everyday clinical practice as part of the contact between the healthcare professional and the patient with type 1 diabetes mellitus. An interactive Web-based calculator to facilitate this is available at www.steno.dk/T1RiskEngine. See p 1058.
Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES)
Familial hypercholesterolemia (FH) is an autosomal-dominant genetic cholesterol disorder associated with premature atherosclerotic cardiovascular disease, with a reported ≈90-fold increase in premature atherosclerotic cardiovascular disease in young adults. Because statins have been shown to lower low-density lipoprotein and to reduce the risk of heart attack in individuals with FH, interest in FH screening and statin use to reduce premature atherosclerotic cardiovascular disease has grown. The population benefit of FH screening, however, depends on the US prevalence of FH, which remains unknown. Recent reports from mostly European populations suggest prevalences between 1 in 137 and 1 in 500. Applying a definition of FH modified from the Dutch Lipid Clinic criteria in nationally representative US data from the National Health and Nutrition Survey (NHANES), we estimated the prevalence of FH to be 1 in 250 (95% confidence interval, 1 in 311 to 209), suggesting that 834 500 US adults have FH. The FH prevalence was similar in men and women but varied by race/ethnicity, with whites and blacks being affected more frequently than Mexican Americans and individuals of other races. The estimated FH prevalence was also higher in older ages and in the presence of obesity, a finding not typical of an autosomal genetic disorder, suggesting possible worsening lifestyle practices, unmasking of a milder genotype, or a physiological increase in low-density lipoprotein cholesterol levels resulting from age or menopause. Genetic testing in a nationally representative sample would improve the accuracy of our FH prevalence estimates, which rely on clinical criteria. See p 1067.
Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy: 20-Year Follow-Up of West of Scotland Coronary Prevention Study
Adoption of statin therapy for the primary prevention of cardiovascular disease is an area of controversy in clinical practice. There is perceived uncertainty about long-term efficacy with respect to vascular and all-cause mortality and the long-term safety of treatment. The findings of the present study should help alleviate at least some of these concerns. Extended follow-up of this primary prevention trial in high-risk men with raised low-density lipoprotein cholesterol but without a history of myocardial infarction demonstrated a long-term legacy benefit of low-density lipoprotein lowering by statin therapy with a significant reduction in cardiovascular mortality and improved survival when viewed over the entire 20 years of follow-up. Furthermore, the reduction in cumulative cardiovascular events, representing the total burden of disease, was substantial both numerically (with attendant economic savings) and clinically in terms of relative risk across a range of cardiovascular outcomes. The finding of a late posttrial benefit of a reduced risk of heart failure gives further impetus to the need to start treatment early. These long-term efficacy findings, particularly for all-cause mortality, and detailed safety data should allay concerns over strategies to promote the more widespread use of statins in the population. See p 1073.
Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction
Myocardial infarction (MI) is a major cause of heart failure and death in the United States. Despite current available treatments, the outcome of MI remains poor. Extensive research and clinical trials have been devoted to developing methods for the generation of new cardiac muscle cells (cardiomyocytes) after MI. In the past, proliferation of resident adult cardiomyocytes was not thought to be an effective way to repair or regenerate injured heart muscle. However, recent reports demonstrate that adult differentiated cardiomyocytes have the ability to proliferate, albeit at low frequency, supporting the stimulation of existing myocardium as an attractive strategy for cardiac regeneration after MI. Here, we report the novel finding that enhanced expression of the transcription factor Tbx20 specifically in differentiated adult cardiomyocytes promotes myocyte proliferation and repair after MI in vivo in mice. In the developing heart, Tbx20 is required for prenatal cardiomyocyte proliferation. Interestingly, proliferating cardiomyocytes induced by Tbx20 overexpression in adults have fetal-like characteristics, including smaller size, mononucleation, and fetal contractile protein expression, without adverse effects on cardiac function in the long term. Strikingly, Tbx20 overexpression induced after MI significantly improves survival, preserves cardiac function, reduces infarct scar size, and enhances vasculature and cardiomyocyte proliferation. Tbx20 induces cardiomyocyte proliferation by activating proproliferative signaling networks and repressing expression of antiproliferative proteins, including Btg2. Thus, stimulation of adult cardiomyocyte proliferation by factors such as Tbx20 has therapeutic potential to promote heart function and myocardial repair after MI. See p 1081.
Endothelial p110γPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury
The integrity of endothelial monolayer is essential for vascular homeostasis. However, little is known about the signaling pathways regulating regeneration of the endothelial barrier after inflammatory vascular injury. In this study, we have identified a novel function of p110γPI3K expressed in endothelial cells in mediating endothelial regeneration and vascular repair. We showed that endothelial p110γ activation by G protein–coupled receptor signaling after sepsis-induced vascular injury was required for Forkhead box M1 (FoxM1) activation and the resulting repair of the endothelial barrier and resolution of inflammation. Our data also provide evidence of the clear association of acute respiratory distress syndrome with diminished expression of p110γPI3K in pulmonary vascular endothelial cells of patients with acute respiratory distress syndrome. Thus, development of means of activation of p110γPI3k–Forkhead box M1 (FoxM1) signaling may represent a novel strategy for the treatment of inflammatory vascular diseases such as acute lung injury or acute respiratory distress syndrome. See p 1093.
- © 2016 American Heart Association, Inc.
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