Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies

The association between subclinical thyroid dysfunction and cardiovascular outcomes has been recently clarified with the publication of three individual participant data (IPD) analyses from the Thyroid Studies Collaboration. We identified original cohort studies with a systematic review and pooled individual data from over 70'000 participants to obtain a more precise estimate of the risks of cardiovascular outcomes associated with subclinical thyroid dysfunction. Subclinical hypothyroidism and subclinical hyperthyroidism, defined as normal thyroxine (FT4) levels with increased or decreased Thyroid-Stimulating Hormones (TSH or thyrotropin) respectively, are associated with increased risk of cardiovascular outcomes compared to euthyroid state, particularly in those with a more pronounced thyroid dysfunction. Specifically, subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD) events, CHD mortality and heart failure (HF) events in individuals with higher TSH levels, particularly in those with TSH levels ≥10.0 mIU/L. Conversely, subclinical hyperthyroidism is associated with an increased risk of total mortality, CHD mortality, HF and atrial fibrillation, particularly in those with suppressed TSH levels <0.10 mIU/L. Pending ongoing randomized controlled trials, these observational findings allow identifying potential TSH thresholds for thyroid medication initiation based on risk of clinical outcomes, although clinical decision based solely on observational data need caution. The impact of thyroid replacement among the elderly with subclinical hypothyroidism is currently studied in a multicenter international randomized controlled trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial, TRUST trial).

Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

Attributional styles and stress-related atherogenic plasma lipid reactivity in essential hypertension.

OBJECTIVE Hypertension and an atherogenic lipid profile are known risk factors for coronary heart disease (CHD). Hypertensives show greater changes in atherogenic plasma lipids to acute stress than normotensives. In this study, we investigated whether attribution of failure is associated with lipid stress reactivity in hypertensive compared with normotensive men. METHODS 18 normotensive and 17 hypertensive men (mean±SEM; 45±2.2 years) underwent an acute standardized psychosocial stress task that can be viewed as a situation of experimentally induced failure. We assessed external-stable (ES), external-variable (EV), internal-stable (IS), and internal-variable (IV) attribution of failure and psychological control variables (i.e. extent of depression and neuroticism). Moreover, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and norepinephrine were measured immediately before and several times after stress. RESULTS ES moderated TC- and LDL-C-stress reactivity in hypertensives as compared to normotensives (interaction mean arterial pressure [MAP]-by-ES for TC: F=3.71, p=.015; for LDL-C: F=3.61, p=.016). TC and LDL-C levels were highest in hypertensives with low ES immediately after stress (p≤.039). In contrast, hypertensives with high ES did not differ from normotensives in TC and LDL-C immediately after stress (p's>.28). Controlling for norepinephrine, depression, and neuroticism in addition to age and BMI did not significantly change results. There were no significant associations between lipid baseline levels or aggregated lipid secretion and IS, IV, or EV (p's>.23). CONCLUSION Our data suggest that ES may independently protect from elevated lipid stress reactivity in hypertensive individuals. ES thus might be a protective factor against CHD in hypertension.

Coronary collateral function in the transplanted heart: propensity score matching with coronary artery disease

The function of the coronary collateral circulation in heart transplant patients has not been investigated in a controlled fashion. Since it partly belongs to the microcirculation, which is affected by transplant vasculopathy, the hypothesis was tested that the coronary collateral circulation in heart transplant recipients is less developed than in coronary artery disease (CAD) patients.

Determinants of preformed collateral vessels in the human heart without coronary artery disease

Coronary collaterals protect myocardium jeopardized by coronary artery disease (CAD). Promotion of collateral circulation is desirable before myocardial damage occurs. Therefore, determinants of collateral preformation in patients without CAD should be elucidated.

Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; Results from the heart quest cohort study

The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective cohort. This study is aimed to identify the cause of angina in these patients.

Haemodynamic and arrhythmic effects of moderately cold (22 degrees C) water immersion and swimming in patients with stable coronary artery disease and heart failure

AIMS: Data on moderately cold water immersion and occurrence of arrhythmias in chronic heart failure (CHF) patients are scarce. METHODS AND RESULTS: We examined 22 male patients, 12 with CHF [mean age 59 years, ejection fraction (EF) 32%, NYHA class II] and 10 patients with stable coronary artery disease (CAD) without CHF (mean age 65 years, EF 52%). Haemodynamic effects of water immersion and swimming in warm (32 degrees C) and moderately cold (22 degrees C) water were measured using an inert gas rebreathing method. The occurrence of arrhythmias during water activities was compared with those measured during a 24 h ECG recording. Rate pressure product during water immersion up to the chest was significantly higher in moderately cold (P = 0.043 in CHF, P = 0.028 in CAD patients) compared with warm water, but not during swimming. Rate pressure product reached 14200 in CAD and 12 400 in CHF patients during swimming. Changes in cardiac index (increase by 5-15%) and oxygen consumption (increase up to 20%) were of similar magnitude in moderately cold and warm water. Premature ventricular contractions (PVCs) increased significantly in moderately cold water from 15 +/- 41 to 76 +/- 163 beats per 30 min in CHF (P = 0.013) but not in CAD patients (20 +/- 33 vs. 42 +/- 125 beats per 30 min, P = 0.480). No ventricular tachycardia was noted. CONCLUSION: Patients with compensated CHF tolerate water immersion and swimming in moderately cold water well. However, the increase in PVCs raises concerns about the potential danger of high-grade ventricular arrhythmias.

The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease

Objective To evaluate the effect of heart rate reduction by ivabradine on coronary collateral function in patients with chronic stable coronary artery disease (CAD). Methods This was a prospective randomised placebo-controlled monocentre trial in a university hospital setting. 46 patients with chronic stable CAD received placebo (n=23) or ivabradine (n=23) for the duration of 6 months. The main outcome measure was collateral flow index (CFI) as obtained during a 1 min coronary artery balloon occlusion at study inclusion (baseline) and at the 6-month follow-up examination. CFI is the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. Results During follow-up, heart rate changed by +0.2±7.8 beats/min in the placebo group, and by –8.1±11.6 beats/min in the ivabradine group (p=0.0089). In the placebo group, CFI decreased from 0.140±0.097 at baseline to 0.109±0.067 at follow-up (p=0.12); it increased from 0.107±0.077 at baseline to 0.152±0.090 at follow-up in the ivabradine group (p=0.0461). The difference in CFI between the 6-month follow-up and baseline examination amounted to −0.031±0.090 in the placebo group and to +0.040±0.094 in the ivabradine group (p=0.0113). Conclusions Heart rate reduction by ivabradine appears to have a positive effect on coronary collateral function in patients with chronic stable CAD.

Clinical outcome of patients with stable ischaemic heart disease as compared to those with acute coronary syndromes after percutaneous coronary intervention

Aims: To compare clinical outcomes after percutaneous coronary intervention (PCI) between patients with acute coronary syndromes (ACS) and those with stable ischaemic heart disease (SIHD) stratified by anatomic disease complexity (SYNTAX score). Methods and results: Patient-level data from three all-comers PCI trials were pooled. Patients (n=4,204) were stratified by clinical presentation (i.e., ACS or SIHD) and by SYNTAX score (i.e., lowest vs. two highest tertiles). The major adverse cardiac event (MACE) rates of patients with low-risk SIHD (n=531) and high-risk SIHD (n=1,066) were compared with ACS patients (n=2,607), respectively. At two years, the risk of MACE was higher for high-risk SIHD patients (OR 1.34, 95% CI: 1.08-1.66) and lower for low-risk SIHD patients (OR 0.61, 95% CI: 0.43-0.87) compared with ACS patients, respectively. This difference between high-risk SIHD patients and ACS patients was primarily driven by a higher risk of myocardial infarction (OR 1.64, 95% CI: 1.21-2.21), while there was no difference for cardiac death (OR 0.77, 95% CI: 0.49-1.21) or target lesion revascularisation (OR 1.21, 95% CI: 0.91-1.62). Conclusions: In this pooled analysis, the majority of patients undergoing PCI for SIHD (i.e., with SYNTAX score >8) had a higher risk of MACE than patients with ACS. Trial registration: URL: http://www.ClinicalTrials.gov; unique identifier: NCT00297661 (Sirtax), NCT00389220 (Leaders), NCT00114972 (Resolute-AC).

Mortality and safety of catheter ablation for antiarrhythmic drug-refractory ventricular tachycardia in elderly patients with coronary artery disease

As the population ages, recurrent ventricular tachycardia (VT) is increasingly encountered in elderly patients with ischemic heart disease. Radiofrequency catheter ablation is useful for reducing VT therapy in patients with an implantable defibrillator. The utility of radiofrequency catheter ablation in the elderly is not well defined.

Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.

Coronary artery disease, nitric oxide and oxidative stress: the "Yin-Yang" effect--a Chinese concept for a worldwide pandemic

Prevention of coronary artery disease (CAD) and reduction of its mortality and morbidity remains a major public health challenge throughout the "Western world". Recent evidence supports the concept that the impairment of endothelial function, a hallmark of insulin resistance states, is an upstream event in the pathophysiology of insulin resistance and its main corollaries: atherosclerosis and myocardial infarction. Atherosclerosis is currently thought to be the consequence of a subtle imbalance between pro- and anti-oxidants that produces favourable conditions for lesion progression towards acute thrombotic complications and clinical events. Over the last decade, a remarkable burst of evidence has accumulated, offering the new perspective that bioavailable nitric oxide (NO) plays a pivotal role throughout the CAD-spectrum, from its genesis to the outcome after acute events. Vascular NO is a critical modulator of coronary blood flow by inhibiting smooth muscle contraction and platelet aggregation. It also acts in angiogenesis and cytoprotection. Defective endothelial nitric oxide synthase (eNOS) driven NO synthesis causes development of major cardiovascular risk factors (insulin resistance, arterial hypertension and dyslipidaemia) in mice, and characterises CAD-prone insulin-resistant humans. On the other hand, stimulation of inducible nitric oxide synthase (iNOS) and NO overproduction causes metabolic insulin resistance and characterises atherosclerosis, heart failure and cardiogenic shock in humans, suggesting a "Yin-Yang" effect of NO in the cardiovascular homeostasis. Here, we will present a concise overview of the evidence for this novel concept, providing the conceptual framework for developing a potential therapeutic strategy to prevent and treat CAD.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

Added value of coronary artery calcium score as an adjunct to gated SPECT for the evaluation of coronary artery disease in an intermediate-risk population

The coronary artery calcium (CAC) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease (CAD). The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population. METHODS: Seventy-seven prospectively recruited patients with intermediate risk (as determined by the Framingham Heart Study 10-y CAD risk score) and referred for coronary angiography because of suspected CAD underwent stress (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging (MPI) and CT CAC scoring within 2 wk before coronary angiography. The sensitivity and specificity of SPECT alone and of the combination of the 2 methods (SPECT plus CAC score) in demonstrating significant CAD (>/=50% stenosis on coronary angiography) were compared. RESULTS: Forty-two (55%) of the 77 patients had CAD on coronary angiography, and 35 (45%) had abnormal SPECT results. The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results (889 +/- 836 [mean +/- SD] vs. 286 +/- 335; P < 0.0001). Similarly, with rising CAC scores, a larger percentage of patients had CAD. Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT. SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76% and 91%, respectively. Combining SPECT with the CAC score (at a cutoff of 709) improved the sensitivity of SPECT (from 76% to 86%) for the detection of CAD, in association with a nonsignificant decrease in specificity (from 91% to 86%). CONCLUSION: The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results.

Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease

BACKGROUND: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. METHODS: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well-developed collaterals (CFI>or=0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. RESULTS: The expression of 203 genes significantly correlated with CFI (p = 0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p = 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor beta-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (>or=0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. CONCLUSIONS: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.