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The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular... more
The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (IMA) to endogenous vasoconstrictors in women, resulting in a predilection to myocardial ischemia. This study evaluated sex differences in serotonin and thromboxane A dependent vasoconstriction in human isolated IMA, with the mechanistic role of (1) the endothelium, (2) nitric oxide (NO), (3) prostaglandins, and (4) receptor activity investigated for any observed sex difference. Viable isolated human IMA segments were obtained from 116 patients (44 women [mean age, 66.8±12.2 years] and 72 men [mean age, 66.6±10.4 years]) undergoing coronary artery bypass grafting. Cumulative concentration-response curves for serotonin and thromboxane A mimetic, U46619, were determined and revealed an increased sensitivit...
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The clinical presentation of panic disorder and panic attack overlaps many symptoms typically experienced in coronary heart disease (CHD). Etiological links between panic disorder and CHD are controversial and remain largely tenuous. This... more
The clinical presentation of panic disorder and panic attack overlaps many symptoms typically experienced in coronary heart disease (CHD). Etiological links between panic disorder and CHD are controversial and remain largely tenuous. This systematic review aims to pool together data regarding panic disorder with respect to incident CHD or myocardial infarction. Electronic databases (MEDLINE, EMBASE, PsycINFO and SCOPUS) will be searched using a search strategy exploding the topics for CHD and panic disorder. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: persons without CHD who meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms; Comparison: persons without CHD who do not meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms; verified fatal and non-fatal CHD at follow-up;...
Perhexiline is a unique anti-anginal agent that is frequently used in the treatment of chronic refractory angina. Its utility has been limited because of its complex pharmacokinetics that were only appreciated following the development of... more
Perhexiline is a unique anti-anginal agent that is frequently used in the treatment of chronic refractory angina. Its utility has been limited because of its complex pharmacokinetics that were only appreciated following the development of a therapeutic perhexiline assay. Perhexiline is cleared primarily via formation of mono-hydroxy metabolites (OH-perhexiline) by cytochrome P450 2D6 (CYP2D6). Drugs that are inhibitors of CYP2D6 may therefore inhibit perhexiline metabolism, increase plasma perhexiline concentration and may consequently increase the risk of toxicity. We report a case of a rise in perhexiline plasma concentration to a toxic level following the introduction of terbinafine hydrochloride; a moderate CYP2D6 inhibiting drug.
The Coronary Vasomotion Disorders International Study Group (COVADIS) was established to develop international standards for the diagnostic criteria of coronary vasomotor disorders. The first symposium held on the 4-5 September 2013... more
The Coronary Vasomotion Disorders International Study Group (COVADIS) was established to develop international standards for the diagnostic criteria of coronary vasomotor disorders. The first symposium held on the 4-5 September 2013 addressed the criteria for vasospastic angina, which included the following (i) nitrate-responsive angina, (ii) transient ischaemic electrocardiogram changes, and (iii) documented coronary artery spasm. Adoption of these diagnostic criteria will improve the clinical diagnosis of this condition and facilitate research in this field.
Anticardiolipin antibodies (aCL) are associated with accelerated coronary atherosclerosis. Beta2-glycoprotein 1 is a cofactor necessary for the binding of aCL. The aim of this study was to determine whether antibodies to... more
Anticardiolipin antibodies (aCL) are associated with accelerated coronary atherosclerosis. Beta2-glycoprotein 1 is a cofactor necessary for the binding of aCL. The aim of this study was to determine whether antibodies to beta2-glycoprotein 1 (anti-beta2GP1) predispose to coronary artery disease (CAD), and whether the measurement of anti-beta2GP1 will be more useful than aCL alone in the evaluation of coronary risk. Persons who had undergone coronary angiography were invited to participate, and risk factors for coronary atherosclerosis recorded. IgG aCL and anti-beta2GP1 were measured and fasting triglyceride (TG) and total cholesterol (TC) levels were determined. Angiographic score (AS) was defined as the number of diseased vessels (0, 1, 2, 3), (>50% stenosis). Ethics Committee approval was obtained. Statistical comparison used the Student's t test and Chi-squared test. Ninety-seven subjects (63 male) with age range 38-81 years (mean 66.0) participated. There were 31 subject...
The development of troponin assays with increased diagnostic sensitivity and greater analytic precision has improved the diagnosis of myocardial infarction in high risk patients. However for those patients at intermediate or low risk in... more
The development of troponin assays with increased diagnostic sensitivity and greater analytic precision has improved the diagnosis of myocardial infarction in high risk patients. However for those patients at intermediate or low risk in whom a small troponin rise is detected, a cascade of clinical decisions and investigations could result; potentially having uncertain impact on recurrent ischemic events and increasing bleeding risk and resource utilization. Clinical equipoise remains as to the clinical utility of high sensitivity troponin. We designed a pragmatic randomized clinical trial to evaluate the short and long term clinical impact and resource implications of high sensitivity 5th generation troponin T reporting compared with 4th generation troponin T reporting. Two thousand patients presenting with a suspected acute coronary syndrome were randomized and risk stratified in 5 metropolitan emergency departments in South Australia, Australia. Clinical events occurring after the first 24 h and within 30 days were assessed as the primary endpoint with subsequent events evaluated at 6 and 12 months. The true translational benefits of innovations in diagnostic testing need to be evaluated in robust clinical trials as they can be costly to introduce and the adoption process often focuses on sensitivity and specificity at the expense of measuring improvements in clinical outcome. The results of this study will provide valuable information on contemporary patterns of troponin utilization on the heterogeneous population of chest pain patients presenting to emergency departments, while providing important information from the clinical practice setting for health administrators, government and policy makers.
Considerable focus has been directed towards coronary arterial disease in the management of coronary heart disease, however the coronary microcirculation plays a major role in the regulation of coronary blood flow. Thus while we have... more
Considerable focus has been directed towards coronary arterial disease in the management of coronary heart disease, however the coronary microcirculation plays a major role in the regulation of coronary blood flow. Thus while we have multiple medical and revascularisation therapies to treat large vessel coronary artery disease, therapies directed towards the microcirculation are very limited. This review paper summarises important aspects of coronary microvascular dysfunction including (a) methods of assessment, (b) clinical classification of associated disorders, (c) possible pathophysiological mechanisms, and (d) potential therapies. Hence this will provide important background to advancing our understanding and management of coronary heart disease by targeting the coronary microcirculation.
ABSTRACT Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an enigma that is being increasingly recognized with the more common use of angiography during acute Myocardial Infarction (AMI). Many... more
ABSTRACT Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an enigma that is being increasingly recognized with the more common use of angiography during acute Myocardial Infarction (AMI). Many previous reviews have implicated high prevalence of women and multiple pathogenetic mechanisms in patients with MINOCA. Despite this, clinical and prognostic features remain illusive. Objectives: The objective of this study is to examine the clinical features and pathological mechanisms of MINOCA by undertaking a structured systematic review of the published data. Methods: A literature search for original data was conducted using PubMed and Embase for the search terms ‘Myocardial Infarction’, ‘non-obstructive coronaries’ and ‘coronary angiography’. Inclusion criteria for data were (i) large cohort (n ≥100 patients), (ii) consecutive patient recruitment and (iii) evidence of AMI. Prevalence and clinical characteristics were pooled across studies using random effects meta-analysis models or overall percentages. Results: In the 27 published prevalence studies included in this analysis, 7% of the 177,497 AMI patients fulfilled the MINOCA criteria representing the largest cohort of MINOCA patients (n=12,465) available in the literature. The mean age of MINOCA patients were 54 years with only 40% being women. Cardiovascular risk factors in the MINOCA cohort included hypertension (44%), smoking (42%), hypercholesterolaemia (33%) and diabetes (13%). In-hospital death was reported as 1% of patients while one-year follow up studies revealed cardiac death in 5% (range 0-6%) of MINOCA patients. In 20 published mechanistic studies, coronary spasm was identified in 27%, and hyper-coagulable disorders in 14%. In 28 published Cardiac Magnetic Resonance Imaging studies, non-diagnostic features were revealed in 25% of patients with other diagnoses including AMI (23%), myocarditis (33%), Takotsubo cardiomyopathy (18%) and other forms of cardiomyopathy (6%). Conclusion: In the largest cohort of MINOCA patients, this systematic review reveals a prevalence of 7% amongst AMI patients, with males more often being affected and a spectrum of disorders potentially being responsible for the presentation.
Previous studies reported a reduced coronary blood flow reserve, assessed by the intravenous administration of dipyridamole, in patients with angina and normal coronary arteries, and early after successful coronary angioplasty, which... more
Previous studies reported a reduced coronary blood flow reserve, assessed by the intravenous administration of dipyridamole, in patients with angina and normal coronary arteries, and early after successful coronary angioplasty, which suggests the presence of small coronary vessel dysfunction. This study aimed to establish whether the mechanisms of small coronary vessel disease in these two groups of patients are similar. The effects of the intracoronary infusion of adenosine and dipyridamole (maximum dose 2.7 and 7.5 mg/min, respectively) on coronary blood flow velocity were assessed in 11 patients with angina and normal coronary arteries (group A) and in 12 patients immediately after successful coronary angioplasty (group B) using a 0.018" Doppler wire. Baseline coronary blood flow velocity was significantly higher in group B than group A (34 +/- 14 versus 19 +/- 8 cm/s; P = 0.001). In group A, coronary blood flow velocity was higher during adenosine than dipyridamole infusion (74 +/- 17 versus 58 +/- 21 cm/s; P < 0.001), whereas in group B velocities were similar (85 +/- 30 versus 78 +/- 32 cm/s; NS). In patients with angina and normal coronary arteries, a maximal dose of adenosine causes a greater coronary dilation than that of dipyridamole. Given that dipyridamole operates mainly through an inhibition of adenosine re-uptake, it can only dilate the arteriolar segments exposed to endogenous adenosine. Therefore, the lower response to dipyridamole than to exogenous adenosine observed in patients with angina and normal coronary arteries suggests an impairment of the pre-arterioles that are not influenced by endogenous adenosine, resulting in a limited flow-mediated dilation in response to arteriolar dilation. Such an impairment is not apparent immediately after successful coronary angioplasty, where the most obvious abnormality is an increase of baseline coronary blood flow velocity.
Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards... more
Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards exist. Furthermore, patient-centered outcomes and longitudinal outcomes are under-represented in current assessments. The nonprofit International Consortium for Health Outcomes Measurement (ICHOM) convened an international Working Group to define a consensus standard set of outcome measures and risk factors for tracking, comparing, and improving the outcomes of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the ICHOM Working Group defined who should be tracked, what should be measured, and when such measurements should be performed. The ICHOM CAD consensus measures were designed to be relevant for all patients diagnosed with CAD, including those with acute myocardial infarction, angina, and asymptomatic CAD. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient-reported health status (Seattle Angina Questionnaire [SAQ-7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ-2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons. ICHOM recommends that this set of outcomes and other patient information be measured for all patients with CAD.
The clinical presentation of panic disorder and panic attack overlaps many symptoms typically experienced in coronary heart disease (CHD). Etiological links between panic disorder and CHD are controversial and remain largely tenuous. This... more
The clinical presentation of panic disorder and panic attack overlaps many symptoms typically experienced in coronary heart disease (CHD). Etiological links between panic disorder and CHD are controversial and remain largely tenuous. This systematic review aims to pool together data regarding panic disorder with respect to incident CHD or myocardial infarction. Electronic databases (MEDLINE, EMBASE, PsycINFO and SCOPUS) will be searched using a search strategy exploding the topics for CHD and panic disorder. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: persons without CHD who meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms; Comparison: persons without CHD who do not meet criteria for panic disorder, panic attack, anxiety neurosis or elevated panic disorder symptoms; verified fatal and non-fatal CHD at follow-up;...
Aim: Previous studies demonstrate higher 30-day all-cause mortality and re-infarction amongst women with ST-elevation myocardial infarction (STEMI). This study examines if gender differences exist in cardiac hemodynamic parameters... more
Aim: Previous studies demonstrate higher 30-day all-cause mortality and re-infarction amongst women with ST-elevation myocardial infarction (STEMI). This study examines if gender differences exist in cardiac hemodynamic parameters assessed during an acute STEMI. Methods: The clinical, angiographic and hemodynamic features of 470 consecutive patients undergoing emergency primary percutaneous coronary intervention for an acute STEMI were evaluated with respect to gender. Patients routinely underwent right heart catheterization using a Swan-Ganz catheter, during the emergency reperfusion therapy procedure. Infarct size was estimated by evaluating the peak creatinine kinase (CK) levels. Results: The 135 STEMI female patients were significantly older than males (69±13 vs. 60±12 years, P <0.001) so subsequent analyses were age-adjusted. The findings are summarized below (*p < 0.05, **p<0.001 compared with men). Multivariate logistic regression analysis revealed that pulmonary cap...
Aim: Unlike other cardiovascular disorders, few studies have examined gender differences in health outcomes in peripheral artery disease (PAD) patients. This study assessed whether gender was an independent determinant of health status at... more
Aim: Unlike other cardiovascular disorders, few studies have examined gender differences in health outcomes in peripheral artery disease (PAD) patients. This study assessed whether gender was an independent determinant of health status at (a) initial diagnosis of PAD, (b) 12-month follow-up, or (c) the rate of change over a 12-month period, with the hypothesis that women's PAD health status will be comprised at both time points. Methods: From March'06 to November '10, 588 patients (381 men, 207 women) with newly diagnosed PAD (Rutherford stages I-III) were consecutively enrolled from two vascular clinics in the Netherlands. Clinical details were recorded and patients completed the Short Form 12 (SF-12) questionnaire at baseline and 12 months later. Physical (PCS) and mental component summary (MCS) scores were calculated and compared by gender at each time point and median values were used due to non-normally distributed data. Multivariable linear regression models adjust...
Aim: Delays in reperfusion therapy for ST-elevation myocardial infarction (STEMI) have been associated with an increased mortality. These delays are dependent upon both patient and health system factors. The objective of this study was to... more
Aim: Delays in reperfusion therapy for ST-elevation myocardial infarction (STEMI) have been associated with an increased mortality. These delays are dependent upon both patient and health system factors. The objective of this study was to assess gender differences in door-to-balloon times, in patients undergoing percutaneous coronary intervention (PCI) for STEMI, with respect to its logistical components and evaluate its relationship to 30-day cardiac events (death and/or re-infarction). Methods: Clinical and logistic parameters were prospectively collected between 2005-10 for 735 STEMI patients undergoing primary PCI at two South Australian teaching hospitals. Particular attention was given to the time of patient hospital arrival to the STEMI team notification (Door-Code time), the time from STEMI notification to first balloon inflation (Code-Balloon time), and conventional Door-to-balloon time. Infarct size was estimated by extent of ST elevation on admission and peak creatine kin...
Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on the status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction.... more
Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on the status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction. We examined sex difference in stress, contributing factors to this difference, and whether this difference helps explain sex-based disparities in 1-month recovery using data from 3572 patients with acute myocardial infarction (2397 women and 1175 men) 18 to 55 years of age. The average score of the 14-item Perceived Stress Scale at baseline was 23.4 for men and 27.0 for women (P<0.001). Higher stress in women was explained largely by sex differences in comorbidities, physical and mental health status, intrafamily conflict, caregiving demands, and financial hardship. After adjustment for demographic and clinical characteristics, women had worse recovery than men at 1 month after acute myocardial infarction, with mean differences in improvement scor...
Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (AMI). The degree to which depression is present among younger patients with an AMI, the patient profile... more
Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (AMI). The degree to which depression is present among younger patients with an AMI, the patient profile associated with being a young AMI patient with depressive symptoms, and whether relevant sex differences exist are currently unknown. The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study enrolled 3572 patients with AMI (67.1% women; 2:1 ratio for women to men) between 2008 and 2012 (at 103 hospitals in the United States, 24 in Spain, and 3 in Australia). Information about lifetime history of depression and depressive symptoms experienced over the past 2 weeks (Patient Health Questionnaire; a cutoff score ≥10 was used for depression screening) was collected during index AMI admission. Information on demographics, socioeconomic status, cardiovascular risk, AMI severity, perceived stress (14-item Perceived Stress Scale), a...
We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction and whether or not this association persists following sequential adjustment for... more
We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease, given that aggressive symptom control is a cornerstone of care in those with known coronary disease. A total of 3501 acute myocardial infarction patients (2349 women) aged 18-55 years were enrolled from 103 US/24 Spanish hospitals (2008-2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic (Short Form-12, EuroQoL) and disease-specific (Seattle Angina Questionnaire) measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower ...
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month... more
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder. Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% con...
Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self-reported health status at PAD diagnosis and 12-months later, and... more
Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self-reported health status at PAD diagnosis and 12-months later, and explored (2) whether outcomes in women with PAD differ with regard to long-term major adverse events. A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form-12 (SF-12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12-months later. Women had similar ages and clinical characteristics, but poorer socio-economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental ( 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12-months, women still r...
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While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were... more
While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were to test the endothelium-dependent vasomotor properties of the LMCA, and to compare these responses to downstream epicardial segments. Thirty patients referred for coronary angiography underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound imaging within a non-critically diseased, left-sided conduit vessel. Macrovascular vasomotor response [change in average lumen area (LA) at baseline and following 5 min of 0.30 µg/min IC salbutamol] and percent atheroma volume (PAV) were evaluated in 30 LMCA, 42 proximal, 109 mid, and 132 distal epicardial coronary segments. In comparison with all other segments, the LMCA had the greatest lumen and vessel areas (P < 0.001), yet the proximal epicardial segments contained the greatest PAV (P < 0.02). The mid and distal epicardial segments displayed significant endothelium-dependent vasodilatation from baseline (P = 0.017 and <0.001, respectively); however, the proximal epicardial and LMCA segments did not (P = 0.45 and 0.16, respectively). Significant segmental vasomotor heterogeneity was noted in all 30 patients, with opposing vasomotor responses between adjacent LMCA and epicardial segments. Across all segments, baseline LA inversely correlated with the % change in LA (r = -0.16, P = 0.0005). Endothelium-dependent vasomotor reactivity is heterogenous within the conduit coronary system. Vascular dynamic responses were less prominent in the larger calibre LMCA and proximal epicardial segments. This may, in part, relate to higher shear stress in smaller, distal segments and yet also may explain the propensity for culprit plaques to cluster proximally.
High aerobic capacity is inversely related to cardiovascular disease morbidity and mortality. Recent studies suggest greater improvements in aerobic capacity with high-intensity interval training (interval) compared to moderate-intensity... more
High aerobic capacity is inversely related to cardiovascular disease morbidity and mortality. Recent studies suggest greater improvements in aerobic capacity with high-intensity interval training (interval) compared to moderate-intensity continuous aerobic exercise (continuous). Therefore we perform a meta-analysis of randomised controlled trials comparing the effectiveness of INTERVAL versus CONTINUOUS in aerobic capacity, amongst patients with stable coronary artery disease (CAD) and preserved ejection fraction We searched PubMed, EMBASE, CINAHL, the Australia and New Zealand Clinical Trials Register, clinicaltrials.gov and TROVE for randomised controlled trials comparing INTERVAL with CONTINUOUS in patients with CAD. Studies published in the English language up to December 2013 were eligible for inclusion. Aerobic capacity, quantified by peak oxygen consumption (VO2peak) post exercise training was extracted and compared post-intervention between INTERVAL and CONTINUOUS by way of a fixed model meta-analysis. Secondary outcomes including anaerobic threshold, blood pressure and high-density lipoproteins (HDL) were also analysed. Six independent studies with 229 patients (n=99 randomised to INTERVAL) were included in the meta-analysis. There was a significantly higher increase in VO2peak following INTERVAL compared to CONTINUOUS (Weighted Mean Difference=1.53 ml•kg(-1)min(-1), 95% CI 0.84 to 2.23) with homogeneity displayed between studies (Chi Squared=2.69; P=0.7). Significant effects of INTERVAL compared to CONTINUOUS were also found for anaerobic threshold but not systolic blood pressure. In patients with CAD, INTERVAL appears more effective than CONTINUOUS for the improvement of aerobic capacity in patients with CAD. However, long-term studies assessing morbidity and mortality following INTERVAL are required before this approach can be more widely adopted.

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