High levels of lipoprotein(a) - assessment and treatment. / Høyt nivå av lipoprotein(a) ­ utredning og behandling.

Approximately 5 % of the population have highly elevated levels of lipoprotein(a) (Lp(a)), which is a genetically determined risk factor for cardiovascular disease. Measuring lipoprotein(a) can improve cardiovascular risk stratification and have consequences for preventive measures. Treatment is targeted at reducing modifiable cardiovascular risk factors, but Lp(a)-lowering drugs are being trialled. This article reviews the management of lipoprotein(a) in clinical practice.

Loss of statin treatment years during pregnancy and breastfeeding periods in women with familial hypercholesterolemia.

BACKGROUND AND AIMS: Women with heterozygous familial hypercholesterolemia (FH) are recommended to initiate statin treatment at the same age as men (from 8 to 10 years of age). However, statins are contraindicated when pregnancy is planned, during pregnancy and breastfeeding. The aim of the study was to determine the duration of pregnancy-related off-statin periods and breastfeeding in FH women. METHODS: A cross-sectional study using an anonymous online self-administered questionnaire was conducted. Women with FH were recruited through Lipid Clinics in Norway and Netherlands and national FH patient organizations. RESULTS: 102 women with FH (n = 70 Norwegian and n = 32 Dutch) were included in the analysis. Total length of pregnancy-related off-statin periods was estimated for 80 women where data were available, and was median (min-max) 2.3 (0-14.2) years. Lost statin treatment time was estimated for 67 women where data were available, and was median (min-max) 18 (0-100)% at mean (SD) age of 31 (4.3) years at last pregnancy. More women breastfed in Norway (83%) and for longer time [8.5 [1-42] months] compared to the Netherlands [63%, p = 0.03; 3.6 (0-14) months, p < 0.001]. Eighty-six percent of the women reported need for more information on pregnancy and breastfeeding in relation to FH. CONCLUSIONS: Young FH women lose years of treatment when discontinuing statins in relation to pregnancy and breastfeeding periods and should be closely followed up to minimize the duration of these off-statin periods. Whether these periods of interrupted treatment increase the cardiovascular risk in FH women needs to be further elucidated.

Long-term arterial complications of chemotherapy in patients with cancer.

The number of cancer survivors has gradually increased in recent decades. However, the cancer survivors are at risk for conditions related to their initial disease and its treatment, i.e. surgery, systemic treatment or radiotherapy. Cardiovascular complications, such as myocardial infarction, are common side effects of these therapies. Cardiovascular damage can occur during treatment or month to years after the initial treatment, as late effect of the cancer treatment. The pathophysiology of these effects is not yet fully understood, but an important part of the cardiovascular complications are thought to be the result of effects of anticancer agents on the structural and functional properties of the endothelium. Because these conditions can result in a high degree of morbidity and mortality, understanding how to improve the prevention, recognition, and treatment of vascular disease is an important medical priority in the care for cancer survivors. This review will focus on the long-term arterial complications of chemotherapy in cancer survivors. It will summarize the epidemiology and pathophysiology of these complications. Furthermore, important long-term clinical conditions related to these effects will be outlined, including cardiovascular risk management in terms of prevention, evaluation and therapy.

Postradiotherapy plasma lutein, alpha-carotene, and beta-carotene are positively associated with survival in patients with head and neck squamous cell carcinoma.

The aim of our study was to compare plasma carotenoids (i.e., biomarkers of fruits and vegetables intake) and tocopherols in 29 head and neck squamous cell carcinoma (HNSCC) patients with 51 healthy controls and to explore the possibility whether these plasma antioxidants could be related to outcome among patients. The patients' blood samples were taken at the end of radiotherapy. We observed that plasma lutein, zeaxanthin, alpha-carotene, beta-carotene, lycopene, and total carotenoids were significantly lower in HNSCC patients than controls. Among the patients, 18 died and 11 were still alive during median follow-up of 55 mo for survivors. We found a significant positive association between postradiotherapy plasma carotenoids (lutein, alpha-carotene, and beta-carotene) and progression-free survival in these patients. This study indicates that increasing postradiotherapy plasma carotenoid concentration may reduce risk of premature death or recurrence of tumor in HNSCC patients. Increasing plasma carotenoid concentration should be done by increasing intake of carotenoid-rich fruits and vegetables, as other studies have shown either no or negative effects due to use of carotenoid supplements.

Predictive value of Q waves on the 12-lead electrocardiogram after reperfusion therapy for ST elevation myocardial infarction.

DESIGN: The data used for the present study were obtained as part of a clinical trial evaluating the effect of thrombus aspiration after primary percutaneous coronary intervention (PCI). SETTING: The study was conducted at a tertiary referral facility for primary PCI at a University Medical Center Groningen in The Netherlands. BACKGROUND: Prognosis after ST elevation myocardial infarction (STEMI) is strongly related to infarct size. METHODS: As part of a randomized clinical trial, the first electrocardiogram (ECG) after primary PCI for STEMI was analyzed for the incidence of Q waves (>0.1 mV) on the 12-lead ECG. Infarct size was measured as area under curve (AUC) of creatine kinase (CK) and CK-myocardial band (CK-MB). RESULTS AND CONCLUSION: Nine hundred thirty-three patients were included, the median number of Q waves on the postprocedural ECG was 3 (interquartile range, 1-4). The number of Q waves on the postprocedural ECG was an independent predictor of infarct size measured either as AUC of CK (P < .001) or AUC of CK-MB (P < .001) and was a significant predictor of mortality during follow-up of 14 months. In conclusion, the number of Q waves on the postprocedural 12-lead ECG after primary PCI for STEMI is a strong predictor of infarct size and long-term mortality.

Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction.

AIMS: We investigated the incidence and sequelae of angiographically visible distal embolization (AVDE) after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction patients treated with aspirin, heparin, clopidogrel, and glycoprotein-IIb/IIIa inhibitors. METHODS AND RESULTS: As part of TAPAS, AVDE was a predefined secondary endpoint. We compared angiographic and clinical characteristics, and outcomes of patients with and without AVDE after PCI. AVDE was present on 6.3% of 883 post-procedural angiograms. Angiographically visible distal embolization was associated with significantly worse outcomes, as expressed by lower myocardial blush grade, impaired ST-segment resolution, and higher enzyme levels (all P

Computer-assisted myocardial blush quantification after percutaneous coronary angioplasty for acute myocardial infarction: a substudy from the TAPAS trial.

AIMS: Myocardial reperfusion after acute myocardial infarction can be angiographically assessed by the myocardial blush grade (MBG) or TIMI Perfusion Grade. These scores are based on subjective human judgement and lead to a score of four categories. A more operator-independent way of scoring myocardial perfusion may facilitate research in this area. METHODS AND RESULTS: We designed the 'Quantitative Blush Evaluator' (QuBE), a computer program which calculates a score for myocardial perfusion. This program will be freely available as open source software. The inter-observer concordance was 97.7%. We calculated values on prospectively collected angiograms in patients with acute ST-elevation myocardial infarction from the TAPAS trial. Quantitative blush evaluator values could be assessed on 790 out of 980 collected angiograms (81%). The QuBE score correlated significantly with MBG as determined by a core lab. The QuBE score predicted complete ST-elevation resolution, low enzyme levels, and 1 year survival (all P < 0.001). Quantitative blush evaluator value was an independent predictor of mortality at 1 year [OR 0.40 (0.17-0.90), P = 0.02]. CONCLUSION: The QuBE program provides a practical, freely available computer-assisted assessment of myocardial perfusion. The QuBE score provides a useful surrogate endpoint in trials of therapies aimed at improving myocardial reperfusion.

The feasibility and safety of routine thrombus aspiration in patients with non-ST-elevation myocardial infarction.

OBJECTIVES: To investigate the feasibility and safety of manual thrombus aspiration in patients undergoing percutaneous coronary intervention (PCI) for non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: Myocardial necrosis in patients with acute coronary syndromes may be a sign of microvascular obstruction, owing to spontaneous or PCI-induced embolization of atherothrombotic material. Manual thrombus aspiration results in improved myocardial reperfusion in patients undergoing PCI for ST-elevation myocardial infarction. Currently, no published data on thrombus aspiration in patients with NSTEMI are available. METHODS: As part of a prospective cohort study, 70 patients undergoing PCI for NSTEMI were treated with thrombus aspiration (Export Aspiration Catheter, Medtronic, Minneapolis, MN). Histopathological analysis was performed on aspirated material. RESULTS: Thrombus aspiration was effective in 58 patients (83%) and resulted in a marked reduction of TIMI-thrombus score 4/5 (40% pre- versus 7% postthrombus aspiration) and increase of the rate of TIMI-flow 3 (36% pre- versus 66% postthrombus aspiration). The incidence of myocardial blush grade 2 and 3 were 39 and 45%, respectively. Distal embolization was visible in three patients (4%) on the final angiogram. CONCLUSION: This study demonstrates that thrombus aspiration in most NSTEMI patients is feasible and safe and is associated with a high rate of retrieval of thrombotic material.

Impact of pretreatment with clopidogrel on initial patency and outcome in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review.

BACKGROUND: The main goal of the initial treatment of ST-segment elevation myocardial infarction is prompt reperfusion of the infarct-related artery. The value of pretreatment with clopidogrel before primary percutaneous coronary intervention is currently unclear. METHODS AND RESULTS: Studies were retrieved through MEDLINE and Cochrane Controlled Trials Register searches over the past 20 years. Two authors independently performed the study selection and data extraction. Randomized controlled studies were included when the research subjects were unselected patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Pilot trials, studies that enrolled patients undergoing rescue percutaneous coronary intervention, and studies with angiographic assessment not performed by a core laboratory or 2 blinded investigators were excluded. Thirty-eight treatment groups, including 8429 patients, were included. Initial patency was higher in treatment groups in which patients received pretreatment with clopidogrel (34.3%; 95% confidence interval, 32.9 to 35.8) compared with those in which patients did not receive clopidogrel before initial coronary angiography (25.8%; 95% confidence interval, 24.5 to 27.1). In multivariate-weighted logistic regression analysis, pretreatment with clopidogrel was an independent predictor of early reperfusion (odds ratio, 1.51; 95% confidence interval, 1.31 to 1.74; P<0.0001) and improved clinical outcome. CONCLUSIONS: Initial patency and clinical outcome were improved in treatment groups that received pretreatment with clopidogrel. These results in patients undergoing primary percutaneous coronary intervention are in line with the experience of pretreatment with clopidogrel in elective patients, non-ST-elevation coronary syndromes, and thrombolytic studies.

Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study.

BACKGROUND: Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year. METHODS: Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833. FINDINGS: Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009). INTERPRETATION: Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

Thrombus aspiration as definitive mechanical intervention for ST-elevation myocardial infarction: a report of five cases.

Thrombus aspiration is an effective adjunctive therapy to prevent distal embolization during primary percutaneous coronary intervention (PCI). In some patients, thrombus aspiration results in complete restoration of flow without significant residual stenosis or plaque rupture at the site of occlusion. It is currently unclear if additional angioplasty with balloon or stenting is necessary in these patients. We present 5 cases in which thrombus aspiration was performed without additional angioplasty as treatment for ST-elevation myocardial infarction. During follow up, no patient had an adverse cardiac event. These cases indicate that thrombus aspiration can be performed safely and effectively as definitive treatment in selected patients.

Thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion. METHODS: We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). RESULTS: A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients. CONCLUSIONS: Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)

A comparison of 2 thrombus aspiration devices with histopathological analysis of retrieved material in patients presenting with ST-segment elevation myocardial infarction.

OBJECTIVES: The objective of this study was to compare 2 manual thrombus aspiration catheters in unselected patients with ST-segment elevation myocardial infarction. BACKGROUND: Distal embolization is common during percutaneous coronary intervention in ST-segment elevation myocardial infarction and can induce impaired myocardial perfusion. Several aspiration thrombectomy devices have been introduced to prevent distal embolization, however, with conflicting clinical results. Currently, it is unclear to what extent this variance in outcome can be explained by device-related factors, such as internal lumen size. METHODS: We performed a prospective cohort study in which patients undergoing primary percutaneous coronary intervention were treated with a large-internal-lumen catheter (Diver, Invatec, Roncadelle, Italy). Outcomes were compared with a matched population of the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) trial, in which patients were treated with a medium-sized catheter (Export, Medtronic, Minneapolis, Minnesota). A histopathological analysis was performed of retrieved material. RESULTS: A total of 160 patients, treated with the Diver (n = 80) or Export (n = 80) aspiration catheter, were enrolled. Effective thrombus aspiration was seen in 70.3% of the patients treated with the Diver catheter versus 81.8% with the Export catheter (p = 0.10) No significant difference was found in myocardial blush grade or electrocardiographic outcome between the 2 devices. Size distribution of retrieved thrombotic particles was similar per device. Erythrocyte-rich thrombi were found in 34.8% of the cases and were predominately seen in patients with low initial Thrombolysis In Myocardial Infarction flow grade (p = 0.008). CONCLUSIONS: A larger internal lumen diameter does not result in retrieval of larger thrombotic particles, nor in improved angiographic or electrocardiographic outcomes.

Impact of electrical neurostimulation on persistent ST elevation after successful reperfusion by primary percutaneous coronary intervention.

AIMS: To study the effect of electrical neurostimulation on the ST segment shift in patients with ST elevation myocardial infarction (STEMI) with residual ST elevation after primary percutaneous coronary intervention (PCI). METHODS: After primary PCI, 38 patients with STEMI were divided into 2 groups. Group 1 received 15 minutes of active neurostimulation after the baseline electrocardiogram (ECG); group 2 received 15 minutes of active neurostimulation after 15 minutes of nonactive neurostimulation. RESULTS: In group 1, ST elevation decreased with neurostimulation from 0.65 +/- 0.56 to 0.55 +/- 0.51 (P = .02) and to 0.50 +/- 0.52 (P = .01) without electrical neurostimulation. In group 2, ST elevation changed without neurostimulation from 0.37 +/- 0.32 to 0.33 +/- 0.30 (P = NS) and to 0.28 +/- 0.27 (P = .01) with electrical neurostimulation. In a posthoc analysis, 17 responders had higher ST elevation at the ECG before active electrical neurostimulation than 21 nonresponders (P = .001). CONCLUSION: Electrical neurostimulation may result in significant additional reduction of ST elevation in STEMI after reperfusion treatment, in particular in patients with marked ST elevation on the first ECG after successful primary PCI.

A quantitative estimate of bare-metal stenting compared with balloon angioplasty in patients with acute myocardial infarction: angiographic measures in relation to clinical outcome.

We performed a systematic review of all randomised controlled trials (RCTs) from the pre-drug-eluting-stent era comparing bare-metal stenting (BMS) with balloon angioplasty in patients with acute myocardial infarction (MI) to examine coronary angiographic parameters of infarct-related vessel patency and to relate the angiographic measures to clinical outcome. The search was restricted to published RCTs in humans. 10 RCTs, (6192 patients) were analysed. Compared with balloon angioplasty, BMS was associated with reduced rates of reocclusion (6.7% vs 10.1%, OR 0.62, 95% CI 0.40 to 0.96, p = 0.03) and restenosis (23.9% vs 39.3%, OR 0.45, 95% CI 0.34 to 0.59, p<0.001), but not with reduced rates of subacute thrombosis (1.7% in both groups). BMS showed a reduction in target vessel revascularisation (TVR; 12.2% vs 19.2%, OR 0.50, 95% CI 0.37 to 0.69, p<0.001), but not in mortality (5.3% vs 5.1%) or reinfarction (3.9% vs 4%). The findings of this study support BMS placement in acute MI. The discrepancy between angiographic and clinical parameters has important implications for future studies investigating further technical improvements in mechanical reperfusion therapy.

One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II.

BACKGROUND: There are conflicting data concerning the effect of treatment with glucose-insulin-potassium (GIK) in ST segment elevation myocardial infarction (STEMI). Early studies showed beneficial effects of GIK, however, recent large sample size trials did not confirm this, or suggested only benefits in patients without heart failure. We aimed to evaluate long-term effects of GIK in patients with STEMI without signs of heart failure, all treated with reperfusion therapy. METHODS: From August 2003 to December 2004, 889 STEMI patients without signs of heart failure were randomized to standard care (N=445) or additional GIK infusion (N=444). Glucose-potassium (20% glucose with 80 mmol potassium/l) was infused at 2 ml/kg body weight per hour for 12 h through a peripheral line. Short-acting insulin was started according to admission glucose and adjusted based on hourly measured glucose. Clinical end points were of number of death, reinfarction and revascularization at 1 year. RESULTS: One year follow-up was available in 864 patients (97.2%), 432 in the GIK group and 432 in the control group. Mortality rate was 5.3% in GIK and 3.9% in control patients, p=0.33. Rates of reinfarction and revascularization 4.6% vs. 4.6% and 15.5% and 15.0%, in GIK vs. control patients. CONCLUSION: In patients with STEMI without signs of heart failure treated with reperfusion therapy, GIK therapy offers no clinical benefit at 1 year.

Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS)--study design.

BACKGROUND AND OBJECTIVE: Embolization of atherothrombotic material is common during percutaneous coronary intervention (PCI) in acute myocardial infarction (MI). This may lead to distal vessel occlusion resulting in impaired myocardial perfusion, which is associated with larger infarct size and increased mortality. Adjunctive devices for PCI to protect the microcirculation have been developed. We intend to determine whether aspiration of thrombotic material before stent implantation of the infarct-related coronary artery results in improved myocardial perfusion compared with conventional primary PCI. STUDY DESIGN: TAPAS is a single-center, prospective, randomized trial with a planned inclusion of 1080 patients with ST-elevation MI. Patients are assigned to treatment with thrombus aspiration with the 6F Export Aspiration Catheter (Medtronic Corporation, Santa Rosa, Calif) or to balloon angioplasty before stent implantation in the infarct-related artery. All patients will be treated medically according to current international guidelines including glycoprotein IIb/IIIa inhibitors before PCI. Randomization will be performed before coronary angiography. The primary end point is angiographic myocardial blush grade of <2. Secondary end points are enzymatic infarct size, ST-segment elevation resolution and persistent ST-segment elevation, postprocedural distal embolization, and Major Adverse Cardiac Events at 30 days and 1 year. IMPLICATIONS: If thrombus aspiration significantly improves myocardial perfusion, it will lend support to the use of this treatment as part of the standard approach in patients with acute MI.