S. Ben Freedman

Participating in cardiac rehabilitation: a systematic review and meta-synthesis of qualitative data

Background: Participation in cardiac rehabilitation (CR) benefits patients with coronary heart disease (CHD), yet worldwide only some 15–30% of those eligible attend. To improve understanding of the reasons for poor participation we undertook a systematic review and meta-synthesis of the qualitative literature. Methods: Qualitative studies identifying patient barriers and enablers to attendance at CR were identified by searching multiple electronic databases, reference lists, relevant conference lists, grey literature, and keyword searching of the internet (1990–2010). Studies were selected if they included patients with CHD and reviewed experience or understanding about CR. Meta-synthesis was used to review the papers and to synthesize the data. Results: From 1165 papers, 34 unique studies were included after screening. These included 1213 patients from eight countries. Study methodology included interviews (n = 25), focus groups (n = 5), and mixed-methods (n = 4). Key reasons for not attending CR were physical barriers, such as lack of transport, or financial cost, and personal barriers, such as embarrassment about participation, or misunderstanding the reasons for onset of CHD or the purpose of CR. Conclusions: There is a vast amount of qualitative research which investigates patients’ reasons for non-attendance at CR. Key issues include system-level and patient-level barriers, which are potentially modifiable. Future research would best be directed at investigating strategies to overcome these barriers.

Serum Amyloid A Induces Monocyte Tissue Factor

C-reactive protein (CRP) and serum amyloid A (SAA) increase in the blood of patients with inflammatory conditions and CRP-induced monocyte tissue factor (TF) may contribute to inflammation-associated thrombosis. This study demonstrates that SAA is a potent and rapid inducer of human monocyte TF. SAA induced TF mRNA in PBMC within 30 min and optimal procoagulant activity within 4 h, whereas CRP (25 μg/ml)-induced activity was minimal at this time. Unlike CRP, SAA did not synergize with LPS. Procoagulant activity was inhibited by anti-TF and was dependent on factors VII and X, and TF Ag levels were elevated on CD14+ monocytes. Responses were optimal with lymphocytes, although these were not obligatory. Inhibitor studies indicate activation of NF-κB through the ERK1/2 and p38 MAPK pathways; the cyclo-oxygenase pathway was not involved. SAA-induced TF was partially inhibited by high-density lipoprotein, but not by low-density lipoprotein or by apolipoprotein A-I. SAA is a ligand for the receptor for advanced glycation end products (RAGE), and TF generation was suppressed by ∼50% by a RAGE competitor, soluble RAGE, and by ∼85% by anti-RAGE IgG. However, another RAGE ligand, high mobility group box-1 protein, capable of inducing monocyte chemotactic protein-1 mRNA in 2 h, did not induce TF within 24 h. Cross-linking studies confirmed SAA binding to soluble RAGE. Elevated SAA is a marker of disease activity in patients with rheumatoid arthritis, and PBMC from patients with rheumatoid arthritis were more sensitive to SAA than normals, suggesting a new link between inflammation and thrombosis.

The mobile revolution—using smartphone apps to prevent cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Mobile technology might enable increased access to effective prevention of CVDs. Given the high penetration of smartphones into groups with low socioeconomic status, health-related mobile applications might provide an opportunity to overcome traditional barriers to cardiac rehabilitation access. The huge increase in low-cost health-related apps that are not regulated by health-care policy makers raises three important areas of interest. Are apps developed according to evidenced-based guidelines or on any evidence at all? Is there any evidence that apps are of benefit to people with CVD? What are the components of apps that are likely to facilitate changes in behaviour and enable individuals to adhere to medical advice? In this Review, we assess the current literature and content of existing apps that target patients with CVD risk factors and that can facilitate behaviour change. We present an overview of the current literature on mobile technology as it relates to prevention and management of CVD. We also evaluate how apps can be used throughout all age groups with different CVD prevention needs.

Pleiotropic Roles of S100A12 in Coronary Atherosclerotic Plaque Formation and Rupture

Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca2+-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn2+, we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn2+; a novel Ab was generated that specifically recognized this complex. By chelating Zn2+, S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn2+-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn2+.

Angiographic severity of coronary narrowing is a surrogate marker for the extent of coronary atherosclerosis

Most acute coronary events occur because of narrowings at sites of angiographically minor plaque. Despite this, angiograms are reported in terms of the number of coronary arteries with severe narrowings. Disease severity is correlated with prognosis, but this may simply be due to a strong positive correlation between the severity and extent of coronary atheroma. We therefore aimed to assess the relation between the severity and the extent of coronary atherosclerosis. Coronary angiograms of 350 consecutive patients referred for elective cardiac catheterization were analyzed. Two independent observers calculated the number of arteries with > or = 70% stenosis, a disease severity score, and an extent score (percentage of the coronary artery length with any luminal irregularity). There were no obstructive stenoses in 123 patients (35%); 91 (26%) had 1-vessel disease, 81 (23%) had 2-vessel disease, and 55 (16%) had 3-vessel coronary artery disease. The median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8), and the median extent score was 66% (lower, upper quartile 32, 83; range 0% to 100%). There was a strong linear relation between severity score and extent score (r = 0.62, p < 0.001); however, the data were better described by 2 intersecting straight lines, with a steeper increase in disease severity when the extent score was between 80% and 90% (F1;121 = 6.9, p = 0.001). The severity of coronary disease is therefore significantly correlated with disease extent. This may explain the observed relation between the number of arteries with obstructive stenoses and subsequent risk, even though most events occur at sites of minor plaque.

Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes.

AIMS Elevated serum amyloid A (SAA) levels, like C-reactive protein (CRP), predict coronary events. Both induce monocyte tissue factor (TF), and peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease (CAD) express higher TF in response to CRP. This study examined SAA induction of TF and tumour necrosis factor-alpha (TNF) in PBMC from patients with CAD and in monocytoid THP-1 cells. METHODS AND RESULTS PBMC from 26 males with CAD (15 stable angina, SA, and 11 acute coronary syndromes, ACS) and 14 male controls were stimulated with SAA. SAA promoted up to six-fold increase in TF activity (recalcification assay) on PBMC from patients, associated with elevated TF mRNA and protein. PBMC responded optimally when monocytes were adherent. Unlike CRP, SAA induced TF and TNF in THP-1 cells. SAA-induced TNF was dose-dependently inhibited by HDL. PBMC from patients with ACS expressed more basal TF (257.4+/-46.8 mU/10(6) PBMC vs. 131.0+/-12.5 mU/10(6) PBMC, P=0.003), and greater SAA-induced TF than cells from controls, whereas no difference was found between SA and controls (ACS 2246+/-493, SA 1364+/-206, controls 1091+/-113 mU/10(6) PBMC, with SAA 250 ng/mL, P=0.002 ACS vs. controls across the dose range). Importantly, SAA-induced TNF levels (ELISA) were much higher in patients with ACS than SA or controls (ACS 211+/-41, SA 108+/-16, controls 73+/-11 pg/mL, with SAA 250 ng/mL, P=0.001 ACS vs. controls or P=0.013 ACS vs. SA across the dose range). SAA-induced TF and TNF correlated positively with serum SAA levels in CAD, but not controls. CONCLUSIONS SAA is a prothrombotic and proinflammatory mediator in ACS which may contribute to atherogenesis and its complications.

A role for acute-phase serum amyloid A and high-density lipoprotein in oxidative stress, endothelial dysfunction and atherosclerosis.

Abstract The acute-phase protein serum amyloid A (SAA) is a clinically useful marker of inflammation and associates strongly with increased risk of cardiovascular events. Chronically elevated SAA concentrations may contribute to physiological processes that lead to atherosclerosis, including endothelial dysfunction, an early and predictive event in the development of cardiovascular disease. Accumulating data suggest that SAA can be a direct mediator in the development and progression of atherogenesis and atherothrombosis. SAA may affect key events underlying acute coronary syndromes, including cholesterol transport, contribute to endothelial dysfunction, promote thrombosis, and enhance leukocyte trafficking and activation. This review summarizes the evidence supporting a role for SAA as a potential regulator of inflammation and endothelial dysfunction, which underlie the adverse outcomes that complicate coronary artery disease. The findings suggest that novel therapeutic strategies to reduce SAA levels and/or oppose the actions of SAA may have beneficial effects in patients with coronary artery disease.

Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation

The general public has been conditioned over many years to accept aspirin as an effective, safe, and inexpensive remedy for heart attacks and for primary and secondary prevention of cardiovascular events. In most countries aspirin was available as an over-the-counter remedy well before its widespread use in cardiovascular disease, which probably contributed to its widespread acceptability. Moreover, many physicians took part in the physicians health study,1 a pivotal study of primary prevention in cardiovascular disease, originally promoted as showing that aspirin reduced non-fatal myocardial infarction, but without emphasis of the increase in intracranial haemorrhage and unchanged mortality in this essentially neutral study. In non-valvular atrial fibrillation (AF), aspirin has for a number of years been recommended as thrombo-prophylaxis for those not considered at high risk (see Table 1 , e.g. CHADS2 score <2).2 Unfortunately, the implied benefit of guideline approbation probably led to widespread use of aspirin as the ‘easy’, or ‘soft’ option in those at higher stroke risk with either real or perceived contra-indications to Vitamin K antagonist (VKA, e.g. warfarin). This could be the result of differences in perception among physicians and patients of the risks of stroke vs. bleeding3,4 and also the misperception that aspirin is somewhat effective in stroke prevention in this setting and has lower bleeding risk. Another possible contributory factor may be an exaggerated estimate of VKA-associated bleeding, feared by physicians who do not see the strokes prevented, but do see the bleeds. Coupled with this is the issue that VKA therapy is hard to manage, and appears to be universally disliked by physicians, patients, the media, and industry. Perhaps the connotation with …

Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris

After 2 weeks of nicorandil therapy, time to ischemia on stress testing was significantly less than on day 1 and not different from placebo. These data are consistent with attenuation of the anti-ischemic effects of this drug and suggest that the potassium channel-opening properties do not compensate for development of attenuation to the nitrate component of nicorandil.

Prospective evaluation of the impact of diabetes and left ventricular hypertrophy on the relationship between ischemia and transient ischemic dilation of the left ventricle on single-day adenosine Tc-99m myocardial perfusion imaging

Background. Diabetes and left ventricular hypertrophy (LVH) can cause coronary flow reserve abnormalities in the absence of coronary artery disease (CAD). We sought to evaluate the impact of LVH and diabetes on the relationship between ischemia, severe CAD, and transient ischemic dilation (TID) on adenosine myocardial perfusion imaging (MPI).Methods and Results. We prospectively recruited 157 patients referred for routine single-day adenosine technetium 99m MPI. LVH was assessed by use of transthoracic echocardiography. A ratio of 1.19 or greater on MPI defined TID in men and 1.31 or greater in women. Summed difference scores were determined by use of a 17-segment 5-point scoring system. TID was present in 22 of 157 patients (14%), diabetes in 54 of 157 (34%), and LVH in 42 of 157 (27%). By multivariate logistic regression, LVH, ischemia (summed difference score >2), and diabetes were independently predictive of TID. The incidence of TID was stratified by the presence or absence of diabetes and/or LVH in those with ischemia on MPI (8/8 [100%] vs 0/11 [0%], P<.002) or severe CAD on angiography (5/7 [71%] vs 0/8 [0%], P<.01). All those with TID (22/22 [100%]) had either diabetes or LVH (or both).Conclusion. Although this study confirms the association between TID and both ischemia and severe CAD, all patients with TID had diabetes, LVH, or frequently, both, suggesting that the pathophysiology of these disease processes may play an integral role in the manifestation of TID on adenosine MPI.