Genetic studies have evaluated the influence of blood lipid levels on the risk of coronary artery disease (CAD), but less is known about how they are associated with the extent of coronary ...atherosclerosis.
To estimate the contributions of genetically predicted blood lipid levels on the extent of coronary atherosclerosis.
This genetic study included Icelandic adults who had undergone coronary angiography or assessment of coronary artery calcium using cardiac computed tomography. The study incorporates data collected from January 1987 to December 2017 in Iceland in the Swedish Coronary Angiography and Angioplasty Registry and 2 registries of individuals who had undergone percutaneous coronary interventions and coronary artery bypass grafting. For each participant, genetic scores were calculated for levels of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, based on reported effect sizes of 345 independent, lipid-associated variants. The genetic scores' predictive ability for lipid levels was assessed in more than 87 000 Icelandic adults. A mendelian randomization approach was used to estimate the contribution of each lipid trait.
Genetic scores for levels of non-HDL-C, LDL-C, HDL-C, and triglycerides.
The extent of angiographic CAD and coronary artery calcium quantity.
A total of 12 460 adults (mean SD age, 65.1 10.7 years; 8383 men 67.3%) underwent coronary angiography, and 4837 had coronary artery calcium assessed by computed tomography. A genetically predicted increase in non-HDL-C levels by 1 SD (38 mg/dL to convert to millimoles per liter, multiply by 0.0259) was associated with greater odds of obstructive CAD (odds ratio OR, 1.83 95% CI, 1.63-2.07; P = 2.8 × 10-23). Among patients with obstructive CAD, there were significant associations with multivessel disease (OR, 1.26 95% CI, 1.11-1.44; P = 4.1 × 10-4) and 3-vessel disease (OR, 1.47 95% CI, 1.26-1.72; P = 9.2 × 10-7). There were also significant associations with the presence of coronary artery calcium (OR, 2.04 95% CI, 1.70-2.44; P = 5.3 × 10-15) and loge-transformed coronary artery calcium (effect, 0.70 95% CI, 0.53-0.87; P = 1.0 × 10-15). Genetically predicted levels of non-HDL-C remained associated with obstructive CAD and coronary artery calcium extent even after accounting for the association with LDL-C. Genetically predicted levels of HDL-C and triglycerides were associated individually with the extent of coronary atherosclerosis, but not after accounting for the association with non-HDL cholesterol.
In this study, genetically predicted levels of non-HDL-C were associated with the extent of coronary atherosclerosis as estimated by 2 different methods. The association was stronger than for genetically predicted levels of LDL-C. These findings further support the notion that non-HDL-C may be a better marker of the overall burden of atherogenic lipoproteins than LDL-C.
In a randomized trial, over 7000 patients with ST-segment elevation MI were assigned to undergo thrombus aspiration followed by percutaneous coronary intervention or PCI alone. At 1 year, there was ...no significant between-group difference in the rate of death from any cause.
Acute ST-segment elevation myocardial infarction (STEMI) is often caused by intracoronary thrombus formation with blockage of antegrade coronary flow leading to myocardial ischemia and cell death.
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Thrombus burden, reduced coronary flow, and reduced myocardial perfusion are important predictors of a poor clinical outcome, including recurrence of myocardial infarction, stent thrombosis, and death.
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Prompt initiation of antithrombotic therapy in combination with percutaneous coronary intervention (PCI) is the preferred approach to optimize myocardial perfusion and clinical outcomes.
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Coronary-artery thrombus aspiration before PCI reduces the thrombus burden and improves ST-segment resolution and coronary flow.
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To our knowledge, however, no adequately powered randomized . . .
Background In ST-elevation myocardial infarction (STEMI), distal embolization of thrombus material often precludes restoration of normal coronary artery flow. Small-scaled studies have demonstrated ...that intracoronary thrombus aspiration improves flow and myocardial perfusion, but only one larger randomized single-center study has suggested a survival benefit. Thrombus aspiration is widely used in clinical practice and is recommended by international guidelines despite limited evidence. Methods/design The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia is a multicenter, prospective, randomized, controlled, clinical open-label trial based on the Swedish angiography and angioplasty registry (SCAAR) platform with blinded evaluation of end points. A total of 5,000 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) will randomly be assigned either to conventional PCI or to thrombus aspiration followed by PCI. SCAAR will be used as the platform for randomization, allowing a broad population of all-comers in the registry network to be enrolled. All follow-up will also be done in SCAAR and other national registries. The primary end point is time to all-cause death at 30 days. Discussion The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial is the largest trial to date to evaluate the effect of thrombus aspiration on death following PCI in patients with STEMI. We propose the term randomized clinical registry trial to describe the novel entity of using an online national registry as platform for case records, randomization, and follow-up.
Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is ...commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders.
Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines.
Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.
The infrastructure of an established PCI registry was used to conduct a randomized trial comparing manual thrombus aspiration before PCI with PCI alone in patients with STEMI. There was no ...significant difference between the two groups in mortality at 30 days.
One of the most important therapeutic challenges in the management of ST-segment elevation myocardial infarction (STEMI) is the establishment of normal coronary blood flow after percutaneous coronary intervention (PCI). Reduced flow is closely associated with reperfusion injury,
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which can lead to arrhythmias, contractile dysfunction, microvascular impairment, and irreversible myocardial damage.
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Reduced myocardial perfusion is also associated with heart failure and death.
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Coronary-artery thrombus aspiration, a simple, rapidly performed, and relatively inexpensive adjunct to PCI, may improve blood flow and resolution of ST-segment elevation,
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although this is not a universal finding.
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Previous studies of thrombus aspiration have not . . .
Routine thrombus aspiration during primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) did not reduce the primary composite endpoint in the "A Randomised ...Trial of Routine Aspiration ThrOmbecTomy With PCI Versus PCI ALone in Patients With STEMI Undergoing Primary PCI" (TOTAL) trial. We aimed to analyse a similar endpoint in "The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia" (TASTE) trial up to 180 days.
In TASTE, 7244 patients with STEMI were randomised to thrombus aspiration followed by PCI or to PCI alone. We analysed the quadruple composite endpoint of cardiovascular death, cardiogenic shock, rehospitalisation for myocardial infarction, or new hospitalisation for heart failure. Furthermore, an extended net-benefit composite endpoint including stent thrombosis, target vessel revascularization or stroke within 180 days was analysed.
The primary quadruple composite endpoint occurred in 8.7 % (316 of 3621) in the thrombus aspiration group compared to 9.3 % (338 of 3623) in the PCI alone group (hazard ratio (HR), 0.93; 95 % confidence interval (CI); 0.80 - 1.09, P = 0.36) and the extended net-benefit composite endpoint in 12.0 % (436) vs. 13.2 % (479) (HR, 0.90; 95 % CI; 0.79 - 1.03, P = 0.12). Stroke within 30 days occurred in 0.7 % (27) vs. 0.7 % (24) (HR, 0.89; 95 % CI; 0.51-1.54, P = 0.68).
A large and an extended composite endpoint analysis from the TASTE trial did not demonstrate any clinical benefit of routine thrombus aspiration during PCI in patients with STEMI. There was no evidence of an increased risk of stroke with thrombus aspiration.
Type D (distressed) personality has been associated with adverse cardiac prognosis and poor emotional well-being in cardiac patients, but it is still unclear what mechanisms link Type D personality ...with poor clinical outcomes in cardiac patients. In the present cohort of Icelandic cardiac patients, we examined potential pathways that may explain this relationship. The objectives were to examine 1) the association between Type D personality and impaired psychological status, and to explore whether this association is independent of disease severity; and 2) the association between Type D personality and an unhealthy lifestyle.
A sample of 268 Icelandic coronary angiography patients (74% males (N = 199); mean age 62.9 years (SD 10.5), range 28-85 years) completed the Type D Scale (DS14), Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS) at hospitalization. Health-related behaviors were assessed 4 months following angiography. Clinical data were collected from medical files.
Type D personality was associated with an increased risk of anxiety (OR 2.97, 95% CI:1.55-5.69), depression (OR 4.01, 95% CI:1.42-11.29), and stress (OR 5.99, 95% CI:3.08-11.63), independent of demographic variables and disease severity. Furthermore, fish consumption was lower among Type Ds, as 21% of Type Ds versus 5% of non-Type Ds consumed fish < 1 a week (p < 0.001). Type D patients were also more likely to smoke at follow-up (22% versus 10%, p = 0.024) and to use antidepressants (17% versus 9%, p = 0.049) and sleeping pills (49% versus 33%, p = 0.019) compared to non-Type Ds. Type D personality was not associated with other health-related behaviors, aside from trends towards less fruit and vegetable consumption, and more weight gain.
Type D personality was associated with psychological distress and an unhealthy lifestyle in Icelandic cardiac patients. Future studies should further investigate the association between Type D personality and health-related behaviors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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