Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors
- Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program
- Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload–Induced Mitochondrial Dysfunction and Heart Failure
- Coronary Angiographic Findings in Acute Ischemic Stroke Patients With Elevated Cardiac Troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study
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Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors
This report shows that elevated baseline serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are associated with increased risk of cardiovascular disease events. The results are based on the study of a random sample of ≈4000 men and women free of previous cardiovascular disease who were followed up from the age of 60 for 15 years. The association between serum PCSK9 and cardiovascular disease persisted after adjustment for traditional cardiovascular disease risk factors, including low-density lipoprotein (LDL) cholesterol. Because it is well known that PCSK9 regulates LDL cholesterol levels, we expected serum PCSK9 to hold prognostic information similar to that of LDL cholesterol and anticipated that adjustment for LDL cholesterol would completely attenuate the association. Unexpectedly, the association was only moderately attenuated. Thus, our results may suggest that elevated PCSK9 is a marker for cardiovascular health beyond LDL cholesterol. If our results are confirmed, serum PCSK9 measurements may in the future help guide identification of individuals who are more likely to benefit from therapeutic inhibition of PCSK9, or serum PCSK9 itself may become a treatment target. See p 1230.
Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program
Elevated pulmonary artery pressure is an established risk factor for adverse clinical outcome across the gamut of cardiopulmonary disease, as well as numerous other conditions. The current definition of pulmonary hypertension requires a mean pulmonary artery pressure (mPAP) ≥25 mm Hg measured during right heart catheterization. However, this diagnostic threshold is based primarily on expert consensus opinion, whereas definitive data establishing the spectrum of clinical risk associated with mPAP are lacking. In the current report, invasive hemodynamic, clinical, and outcome data from 76 cardiac catheterization centers nationally in the Veterans Affairs healthcare system were assembled for 21 727 patients, resulting in the largest database to date analyzing the relationship between mPAP and hard clinical end points. Our findings demonstrate a progressive increase in risk for mortality and hospitalization for mPAP that is observed beginning at ~19 mm Hg. We demonstrate that patients with mPAP of 19 to 24 mm Hg, a subgroup classified currently as normal, are at increased risk of hospitalization and mortality. This effect was observed after adjusting for clinical variables or excluding patients with hemodynamic evidence of left heart failure. These data support expanding the cardiopulmonary hemodynamic range associated with increased clinical risk and suggest that mPAP ≥19 mm Hg can be used for risk stratification of patients with underlying cardiopulmonary disease. Furthermore, these data lay the framework for future prospective investigations examining pulmonary hypertension diagnostic criteria, treatment timing, and prevention in at-risk patients to improve on elevated clinical event rates in patients with pulmonary vascular disease. See p 1240.
Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload–Induced Mitochondrial Dysfunction and Heart Failure
Mitochondria are intracellular organelles involved in metabolism and ATP production that are vitally important in cardiomyocytes. Heart failure is commonly accompanied by mitochondrial dysfunction. Dysfunctional mitochondria are the major source of reactive oxygen species, and trigger both the apoptosis and necrosis of cardiomyocytes. Mitochondrial damage spreads rapidly through depolarization of the mitochondrial membrane potential and causes deterioration of the function of healthy mitochondria. Thus, cardiomyocytes possess robust quality control mechanisms, and autophagy, which degrades protein and organelles through lysosomes, is a major mechanism for the elimination of dysfunctional mitochondria. In this study, we show that both general autophagy and a mitochondria-specific form of autophagy (mitochondrial autophagy) are downregulated after pressure overload and that mitochondrial dysfunction develops only after mitochondrial autophagy is downregulated. Mitochondrial autophagy was induced in response to pressure overload through a mechanism dependent on Drp1, a protein known to mediate mitochondrial fission. Treatment of animals with Tat-Beclin 1 peptide, known to stimulate autophagy through mobilization of endogenous Beclin 1, a protein essential for autophagy, increased the level of mitochondrial autophagy in the heart and partially rescued the animals from the development of pressure overload–induced heart failure. These results suggest that interventions to restore the level of mitochondrial autophagy should be considered for potential treatment for patients with heart failure. See p 1249.
Coronary Angiographic Findings in Acute Ischemic Stroke Patients With Elevated Cardiac Troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study
Current American Heart Association/American Stroke Association treatment guidelines recommend assessing cardiac troponin (cTn) levels in all patients presenting with acute ischemic stroke (AIS) to identify concurrent myocardial ischemia and to evaluate cardiovascular status. Because the underlying pathophysiology of cTn elevation in AIS is not necessarily acute coronary ischemia and aggressive antiplatelet therapy may cause harm, the treating physician is left in a clinical dilemma about the optimal timing and invasiveness of diagnostics and treatment. Here, we report the results of the Troponin Elevation in Acute Ischemic Stroke (TRELAS) study, a prospective, observational study with blinded end-point evaluation. The aim of the TRELAS study was to display the frequency of angiographic evidence of a coronary culprit lesion and of obstructive coronary artery disease in patients with AIS and cTn elevation (>50 ng/L) compared with age- and sex-matched patients with non–ST segment–elevation acute coronary syndrome. The major finding of the presented analysis is that patients with AIS were significantly less likely to have coronary culprit lesions compared with patients with non–ST segment–elevation acute coronary syndrome (24% versus 79%; P<0.001) despite similar baseline cTn levels. Moreover, fewer patients with AIS had evidence of any obstructive coronary artery disease (52% versus 87%; P=0.021) or multivessel disease (≥2 vessels diseased, 28% versus 62%; P=0.013). Therefore, routine invasive diagnostic procedures in AIS patients with elevated cTn do not seem warranted. Further research is needed to define clinical or imaging predictors that allow better identification of AIS patients with elevated cTn resulting from potentially unstable coronary artery disease. See p 1264.
- © 2016 American Heart Association, Inc.
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