Clinical decision aids and computed tomography coronary angiography in patients with suspected acute coronary syndrome.

BACKGROUND: The HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared. METHODS: In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data. RESULTS: Among 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days. CONCLUSIONS: In intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation. TRIAL REGISTRATION NUMBER: NCT02284191.

Early computed tomography coronary angiography and preventative treatment in patients with suspected acute coronary syndrome: A secondary analysis of the RAPID-CTCA trial.

BACKGROUND: Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome. METHODS: In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y12 receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined. RESULTS: In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries. CONCLUSIONS: Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease.

Distinguishing Type 1 from Type 2 Myocardial Infarction by Using CT Coronary Angiography.

Purpose: To determine whether quantitative plaque characterization by using CT coronary angiography (CTCA) can discriminate between type 1 and type 2 myocardial infarction. Materials and Methods: This was a secondary analysis of two prospective studies (ClinicalTrials.gov registration nos. NCT03338504 [2014-2019] and NCT02284191 [2018-2020]) that performed blinded quantitative plaque analysis on findings from CTCA in participants with type 1 myocardial infarction, type 2 myocardial infarction, and chest pain without myocardial infarction. Logistic regression analyses were performed to identify predictors of type 1 myocardial infarction. Results: Overall, 155 participants (mean age, 64 years ± 12 [SD]; 114 men) and 36 participants (mean age, 67 years ± 12; 19 men) had type 1 and type 2 myocardial infarction, respectively, and 136 participants (62 years ± 12; 78 men) had chest pain without myocardial infarction. Participants with type 1 myocardial infarction had greater total (median, 44% [IQR: 35%-50%] vs 35% [IQR: 29%-46%]), noncalcified (39% [IQR: 31%-46%] vs 34% [IQR: 29%-40%]), and low-attenuation (4.15% [IQR: 1.88%-5.79%] vs 1.64% [IQR: 0.89%-2.28%]) plaque burdens (P < .05 for all) than those with type 2. Participants with type 2 myocardial infarction had similar low-attenuation plaque burden to those with chest pain without myocardial infarction (P = .4). Low-attenuation plaque was an independent predictor of type 1 myocardial infarction (adjusted odds ratio, 3.44 [95% CI: 1.84, 6.96]; P < .001), with better discrimination than noncalcified plaque burden and maximal area of coronary stenosis (C statistic, 0.75 [95% CI: 0.67, 0.83] vs 0.62 [95% CI: 0.53, 0.71] and 0.61 [95% CI: 0.51, 0.70] respectively; P ≤ .001 for both). Conclusion: Higher low-attenuation coronary plaque burden in patients with type 1 myocardial infarction may help distinguish these patients from those with type 2 myocardial infarction.Keywords: Ischemia/Infarction, CT Angiography, Quantitative CTClinical trial registration nos. NCT03338504 and NCT02284191 Supplemental material is available for this article. © RSNA, 2022.

Early computed tomography coronary angiography in adults presenting with suspected acute coronary syndrome: the RAPID-CTCA RCT.

BACKGROUND: Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined. OBJECTIVE: To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome. DESIGN: A prospective, multicentre, open, parallel-group randomised controlled trial with blinded end-point adjudication. SETTING: Thirty-seven hospitals in the UK. PARTICIPANTS: Adults (aged ≥ 18 years) presenting to the emergency department, acute medicine services or cardiology department with suspected or provisionally diagnosed acute coronary syndrome and at least one of the following: (1) a prior history of coronary artery disease, (2) a cardiac troponin level > 99th centile and (3) an abnormal 12-lead electrocardiogram. INTERVENTIONS: Early computed tomography coronary angiography in addition to standard care was compared with standard care alone. Participants were followed up for 1 year. MAIN OUTCOME MEASURE: One-year all-cause death or subsequent type 1 (spontaneous) or type 4b (stent thrombosis) myocardial infarction, measured as the time to such event adjudicated by two cardiologists blinded to the computerised tomography coronary angiography ( CTCA ) arm. Cost-effectiveness was estimated as the lifetime incremental cost per quality-adjusted life-year gained. RESULTS: Between 23 March 2015 and 27 June 2019, 1748 participants [mean age 62 years (standard deviation 13 years), 64% male, mean Global Registry Of Acute Coronary Events score 115 (standard deviation 35)] were randomised to receive early computed tomography coronary angiography (n = 877) or standard care alone (n = 871). The primary end point occurred in 51 (5.8%) participants randomised to receive computed tomography coronary angiography and 53 (6.1%) participants randomised to receive standard care (adjusted hazard ratio 0.91, 95% confidence interval 0.62 to 1.35; p = 0.65). Computed tomography coronary angiography was associated with a reduced use of invasive coronary angiography (adjusted hazard ratio 0.81, 95% confidence interval 0.72 to 0.92; p = 0.001) but no change in coronary revascularisation (adjusted hazard ratio 1.03, 95% confidence interval 0.87 to 1.21; p = 0.76), acute coronary syndrome therapies (adjusted odds ratio 1.06, 95% confidence interval 0.85 to 1.32; p = 0.63) or preventative therapies on discharge (adjusted odds ratio 1.07, 95% confidence interval 0.87 to 1.32; p = 0.52). Early computed tomography coronary angiography was associated with longer hospitalisations (median increase 0.21 days, 95% confidence interval 0.05 to 0.40 days) and higher mean total health-care costs over 1 year (£561 more per patient) than standard care. LIMITATIONS: The principal limitation of the trial was the slower than anticipated recruitment, leading to a revised sample size, and the requirement to compromise and accept a larger relative effect size estimate for the trial intervention. FUTURE WORK: The potential role of computed tomography coronary angiography in selected patients with a low probability of obstructive coronary artery disease (intermediate or mildly elevated level of troponin) or who have limited access to invasive cardiac catheterisation facilities needs further prospective evaluation. CONCLUSIONS: In patients with suspected or provisionally diagnosed acute coronary syndrome, computed tomography coronary angiography did not alter overall coronary therapeutic interventions or 1-year clinical outcomes, but it did increase the length of hospital stay and health-care costs. These findings do not support the routine use of early computed tomography coronary angiography in intermediate-risk patients with acute chest pain. TRIAL REGISTRATION: This trial is registered as ISRCTN19102565 and Clinical Trials NCT02284191. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 37. See the NIHR Journals Library website for further project information.

WHY DID WE DO THE RESEARCH?: Chest pain is a common medical emergency. It is important to decide if the cause is a heart attack. The two tests that are often used are a heart recording (electrocardiogram) and a blood test (troponin levels). If both are normal, the cause of chest pain is unlikely to be a heart attack and the patient is often discharged home. If either test is positive or if the patient has had previous heart problems, then the patient may require further investigation. We wanted to test whether or not adding a heart scan called a computerised tomography coronary angiogram improved patients' care. HOW DID WE DO THE RESEARCH?: We carried out a randomised trial in which half of the patients attending hospital with chest pain had a computerised tomography coronary angiography scan as part of their assessment and half of the patients did not. In total, 1749 patients were recruited and followed up for 1 year. BRINGING IT ALL TOGETHER: The use of an additional early computerised tomography coronary angiography scan for chest pain patients of medium risk produced only small improvements in patient care.

Presentation cardiac troponin and early computed tomography coronary angiography in patients with suspected acute coronary syndrome: a pre-specified secondary analysis of the RAPID-CTCA trial.

AIMS: To evaluate the potential associations between presentation cardiac troponin and the clinical impact of early computed tomography coronary angiography (CTCA) in intermediate-risk patients with suspected acute coronary syndrome. METHODS AND RESULTS: In a large multicentre randomized controlled trial of patients with intermediate-risk chest pain due to suspected acute coronary syndrome, early CTCA had no effect on the primary outcome-death or subsequent Type 1 or 4b myocardial infarction-but reduced the rate of invasive coronary angiography. In this pre-specified secondary analysis, cardiovascular testing and clinical outcomes were compared between those with or without cardiac troponin elevation at presentation. Of 1748 patients, 1004 (57%) had an elevated cardiac troponin concentration and 744 (43%) had a normal concentration. Patients with cardiac troponin elevation had a higher Global Registry of Acute Coronary Events score (132 vs. 91; P < 0.001) and were more likely to have obstructive coronary artery disease (59 vs. 33%; P < 0.001), non-invasive (72 vs. 52%; P < 0.001) and invasive (72 vs. 38%; P < 0.001) testing, coronary revascularization (47 vs. 15%; P < 0.001), and the primary outcome (8 vs. 3%; P = 0.007) at 1 year. However, there was no evidence that presentation cardiac troponin was associated with the relative effects of early CTCA on rates of non-invasive (Pinteraction = 0.33) and invasive (Pinteraction = 0.99) testing, coronary revascularization (Pinteraction = 0.57), or the primary outcome (Pinteraction = 0.41). CONCLUSION: Presentation cardiac troponin had no demonstrable associations between the effects of early CTCA on reductions in non-invasive and invasive testing, or the lack of effect on coronary revascularization or the primary outcome in intermediate-risk patients with suspected acute coronary syndrome.

Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial.

OBJECTIVES: To establish if the use of early computed tomography (CT) coronary angiography improves one year clinical outcomes in patients presenting to the emergency department with acute chest pain and at intermediate risk of acute coronary syndrome and subsequent clinical events. DESIGN: Randomised controlled trial. SETTING: 37 hospitals in the UK. PARTICIPANTS: Adults with suspected or a provisional diagnosis of acute coronary syndrome and one or more of previous coronary heart disease, raised levels of cardiac troponin, or abnormal electrocardiogram. INTERVENTIONS: Early CT coronary angiography and standard of care compared with standard of care only. MAIN OUTCOME MEASURES: Primary endpoint was all cause death or subsequent type 1 or 4b myocardial infarction at one year. RESULTS: Between 23 March 2015 and 27 June 2019, 1748 participants (mean age 62 years (standard deviation 13), 64% men, mean global registry of acute coronary events (GRACE) score 115 (standard deviation 35)) were randomised to receive early CT coronary angiography (n=877) or standard of care only (n=871). Median time from randomisation to CT coronary angiography was 4.2 (interquartile range 1.6-21.6) hours. The primary endpoint occurred in 51 (5.8%) participants randomised to CT coronary angiography and 53 (6.1%) participants who received standard of care only (adjusted hazard ratio 0.91 (95% confidence interval 0.62 to 1.35), P=0.65). Invasive coronary angiography was performed in 474 (54.0%) participants randomised to CT coronary angiography and 530 (60.8%) participants who received standard of care only (adjusted hazard ratio 0.81 (0.72 to 0.92), P=0.001). There were no overall differences in coronary revascularisation, use of drug treatment for acute coronary syndrome, or subsequent preventive treatments between the two groups. Early CT coronary angiography was associated with a slightly longer time in hospital (median increase 0.21 (95% confidence interval 0.05 to 0.40) days from a median hospital stay of 2.0 to 2.2 days). CONCLUSIONS: In intermediate risk patients with acute chest pain and suspected acute coronary syndrome, early CT coronary angiography did not alter overall coronary therapeutic interventions or one year clinical outcomes, but reduced rates of invasive angiography while modestly increasing length of hospital stay. These findings do not support the routine use of early CT coronary angiography in intermediate risk patients with acute chest pain and suspected acute coronary syndrome. TRIAL REGISTRATION: ISRCTN19102565, NCT02284191.

Antiplatelet agents and anticoagulants for hypertension.

BACKGROUND: Elevated systemic blood pressure results in high intravascular pressure but the main complications, coronary heart disease (CHD), ischaemic strokes and peripheral vascular disease (PVD), are related to thrombosis rather than haemorrhage. Some complications related to elevated blood pressure, heart failure or atrial fibrillation, are themselves associated with stroke and thromboembolism. Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure. OBJECTIVES: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure, including those with elevations in both systolic and diastolic blood pressure, isolated elevations of either systolic or diastolic blood pressure, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. SEARCH METHODS: Electronic databases (MEDLINE, EMBASE, DARE, CENTRAL, Hypertension Group specialised register) were searched up to January 2011. The reference lists of papers resulting from the electronic searches and abstracts from national and international cardiovascular meetings were hand-searched to identify missed or unpublished studies. Relevant authors of studies were contacted to obtain further data. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment. DATA COLLECTION AND ANALYSIS: Data were independently collected and verified by two reviewers. Data from different trials were pooled where appropriate. MAIN RESULTS: Four trials with a combined total of 44,012 patients met the inclusion criteria and are included in this review. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. In one large trial ASA taken for 5 years reduced myocardial infarction (ARR 0.5%, NNT 200), increased major haemorrhage (ARI 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In one trial there was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death. In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events. The ATC meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1% as compared to placebo. Data on the 10,600 patients with elevated blood pressure from the 29 individual trials included in the ATC meta-analysis was requested but could not be obtained. AUTHORS' CONCLUSIONS: Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit, reduction in myocardial infarction, which is negated by a harm of similar magnitude, increase in major haemorrhage.The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm.Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure. Ticlopidine, clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure. Newer antithrombotic oral drugs such as dabigatran, rivaroxaban, apixaban and endosaban are yet to be tested in patients with high blood pressure.Further trials of antithrombotic therapy including with newer agents and complete documentation of all benefits and harms are required in patients with elevated blood pressure.

Effects of "newer" and "older" antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

BACKGROUND: Different antihypertensive therapies may exert benefits via not only a reduction in blood pressure but also in improving the risk of thrombosis. METHODS: We tested the hypothesis that a more modern antihypertensive drug regimen (ie, amlodipine +/- perindopril) would have a more beneficial effect on hemorheological markers (white blood-cell count [WCC], plasma viscosity [PV], hematocrit [HCT], and fibrinogen)--and on plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation), compared with an older antihypertensive drug regimen (ie, atenolol +/- bendroflumethiazide). RESULTS: After 6 months, PV, sP-sel, and HCT fell in both groups (P < .01), while fibrinogen was unchanged. However, those 74 patients randomized to amlodipine +/- perindopril had significant reductions in WCC (P = .005), with no significant changes in vWF or platelet count. Conversely, in those 85 patients randomized to atenolol +/- bendroflumethiazide, there were significant reductions in vWF (P = .001) and platelet count (P = .011) but no significant reductions in WCC. There were no significant differences in the levels of any of the variables between the two arms of the trial, nor a significant difference in the magnitude of reduction between the two treatment arms. CONCLUSIONS: Within the constraints of this substudy design, there was no differential effect apparent of the two antihypertensive treatment arms on hemorheological parameters or endothelial and platelet function (as assessed by vWF and sP-sel), suggesting that other pathophysiological mechanisms may be involved.

Endothelial function and its assessment.

Endothelial dysfunction is a characteristic aspect of most of the conditions associated with atherosclerosis and is commonly found as an early feature in atherothrombotic vascular disease. An appreciation of the underlying mechanisms of endothelial function, as well as dysfunction, is essential as this has critical influence on the different methods in the assessment of endothelial function and effects of various treatments on its quantification. Furthermore, endothelial dysfunction is recognised as a type of 'target organ damage' in common cardiovascular conditions (e.g., hypertension) and the area is of increasing interest for new drug development, as therapies that modulate the endothelium will have added advantages; thus, for the development of new/experimental drugs, an awareness of ways to assess the endothelium is necessary. In this review, an overview of different methods including biochemical markers, and invasive and non-invasive tools, to determine endothelial function is presented as well as their clinical relevance. Furthermore, the effects of various treatments on endothelial dysfunction and their underlying mechanisms are elucidated.

Relationship of homocysteine to markers of platelet and endothelial activation in "high risk" hypertensives: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

OBJECTIVE: To examine the relationship between plasma homocysteine (HCY) and rheological, endothelial and platelet markers in "high risk" hypertensive patients. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: A total of 165 consecutive hypertensive patients (136 male; mean age 63 years (S.D. 8)) at high risk of cardiovascular disease who screened for inclusion in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) were studied along with 38 population normotensive healthy controls. We measured levels of plasma homocysteine [high pressure liquid chromatography (HPLC)], soluble P-selectin, a marker of platelet function, von Willebrand factor (vWF), an index of endothelial damage/dysfunction [both by ELISA] and fibrinogen (CLAUSS). The Framingham cardiovascular and cerebrovascular risk scores were calculated. RESULTS: Hypertensives had significantly higher blood pressure (BP) [165/90(16/10) vs. 138/82(12/8) mm Hg, p<0.0001], sP-sel [54(44-67) vs. 45(35-57) ng/ml, p=0.002], vWF [133(34) vs. 110(28) IU/dl, p<0.0001], and fibrinogen [2.98(2.52-3.47) vs. 2.43(2.20-2.83)g/l, p=<0.0001]. Homocysteine were lower in our hypertensives compared with controls [8.7(6.9-11.2) vs. 10.5(8.5-13.1) micromol/l, p=0.005], but there were significant correlations between homocysteine levels and both calculated 10-year coronary heart disease risk (Spearman r=0.197, p=0.026) and stroke risk (r=0.210, p=0.018), using the Framingham equation. There was a positive correlation between plasma homocysteine and soluble P-selectin (r=0.180, p=0.025), which persisted in multiple linear regression analysis. There was no significant relationship between homocysteine and HCT, PV, or the endothelial marker, vWF. CONCLUSION: Hypertensives demonstrate abnormalities of endothelial, platelet and rheological function. Homocysteine is related to both 10-year coronary heart disease risk and stroke risk, and is significantly correlated with soluble P-selectin, a marker of platelet activation, in hypertensives but only weakly or not at all to other thrombotic markers. Increased platelet activation as reflected by soluble P-selectin may be one mechanism by which hyperhomocysteinaemia confers an increased thrombotic risk in hypertension.

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]).

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.

Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment.

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring LDL subfractions and flow-mediated dilation (FMD) (reflecting endothelial dysfunction) in a cohort of high-risk hypertensive patients. We studied 84 hypertensive patients (74 men; mean age, 64 years; SD 8). Chylomicron-free LDL subfractions were analyzed by disc polyacrylamide gel electrophoresis, producing an LDL score, with higher scores being equivalent to a greater proportion of the more atherogenic LDL subfractions. High-resolution ultrasound was used to assess endothelium-dependent brachial artery FMD after reactive hyperemia after vessel occlusion. Baseline levels were compared with 61 age- and gender-matched healthy normotensive control subjects. Mean LDL score was higher and FMD impaired in hypertensive subjects compared with control subjects. These indexes were significantly improved after 6 months of cardiovascular risk factor management. LDL score correlated significantly with the 10-year Framingham coronary heart disease risk score, with a negative correlation with FMD (both P<0.001). Abnormal atherogenesis and endothelial dysfunction are both present in hypertension and appear to be related to each other, potentially leading to vascular complications. The abnormal LDL scores also correlate with the 10-year cardiovascular risk and can be positively influenced by cardiovascular risk management.

Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management.

BACKGROUND: Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. These pathophysiologic processes are assessable by measurement of plasma levels of von Willebrand factor (vWf), and by vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). We hypothesized that these markers would correlate with the Framingham cardiovascular risk score and would be responsive to treatment. METHODS: We measured these markers by enzyme-linked immunosorbent assay in 286 patients with hypertension (239 men; mean age 63 years; mean systolic blood pressure [BP]/diastolic BP 162/89 mm Hg) and additional risk factors, and related them to the patient's cardiovascular disease (CVD) and cerebrovascular accident (CVA) risk, using the Framingham equation. Patients were compared with 60 healthy normotensive controls. In 248 patients, the effects of 6 months of intensified cardiovascular risk factor management, including BP and (where appropriate) lipid-lowering treatment, were investigated. RESULTS: Plasma VEGF and vWf levels were higher, but sFlt-1 levels lower (all P <.001), in the hypertensive patients compared with the controls. The VEGF and vWf levels correlated significantly with age, systolic and diastolic BP, 10-year CVD risk, and CVA risk scores (all P <.01), whereas sFlt-1 was negatively correlated with these risk scores (P <.01). After intensified cardiovascular risk factor management, total cholesterol, BP, VEGF, and vWf levels were all reduced, yet sFlt-1 levels increased (all P <.05). CONCLUSIONS: In hypertension, the processes of endothelial damage and angiogenesis are abnormal, and correlate with overall cardiovascular risk. Indices of endothelial damage and angiogenesis are beneficially changed by intensive cardiovascular risk factor management.