Mehmood Butt

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is a common yet an under-diagnosed sleep related breathing disorder affecting predominantly middle-aged men. OSA is associated with many adverse health outcomes, including cardiovascular disease. Common OSA associated/induced cardiovascular disorders include coronary artery disease, heart failure, hypertension, cardiac arrhythmias and stroke, which further increase morbidity and mortality in the OSA population. Endothelial dysfunction, coagulopathy, impaired sympathetic drive, oxidative and inflammatory stress are the pathophysiological pathways suggested for the development of cardiovascular disease in OSA. The evidence would suggest that OSA should be considered as a cardiovascular risk factor, and is a treatable condition. Multiple studies using Continuous Positive Airway Pressure (CPAP) have shown improvements in the clinical state as well as retardation of disease progression. Therefore, patients with cardiovascular disease should be proactively screened for OSA and vice versa.

Left Ventricular Systolic and Diastolic Function in Obstructive Sleep Apnea: Impact of Continuous Positive Airway Pressure Therapy

Background— Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results— A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects ( P <0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness ( P =0.02) and improvement in LV ejection fraction ( P <0.05), systolic S velocity ( P <0.05), and diastolic LV impairment parameters. Conclusions— Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.Background—Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results—A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects (P<0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness (P=0.02) and improvement in LV ejection fraction (P<0.05), systolic S velocity (P<0.05), and diastolic LV impairment parameters. Conclusions—Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.

Myocardial Perfusion by Myocardial Contrast Echocardiography and Endothelial Dysfunction in Obstructive Sleep Apnea

Obstructive sleep apnea is associated with increased cardiovascular morbidity and mortality. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial dysfunction in normotensive subjects with moderate-to-severe obstructive sleep apnea, who were compared with hypertensive and healthy subjects, as well as the impact of continuous positive airway pressure treatment on obstructive sleep apnea subjects. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), cutaneous perfusion responses to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, and circulating endothelial and endothelial progenitor cells in a total of 108 subjects (n=36 each of matched obstructive sleep apnea, hypertension, and healthy cohorts). Subjects with obstructive sleep apnea and hypertension demonstrated abnormal myocardial perfusion (P<0.001 for both comparisons), attenuated brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) compared with healthy individuals. Both hypertensive and obstructive sleep apnea patients showed significant improvements in myocardial perfusion (P<0.01), brachial artery reactivity (P<0.001), and cutaneous perfusion responses (P<0.001) after 26 weeks of continuous positive airway pressure therapy. There were no significant differences in pulse wave velocity and endothelial cells across the 3 groups. Concomitant endothelial dysfunction and impaired myocardial perfusion are present in otherwise normal subjects with moderate-to-severe obstructive sleep apnea, and effective continuous positive airway pressure treatment reverses many of these macrovascular/microvascular abnormalities.

Persistent Macrovascular and Microvascular Dysfunction in Patients With Malignant Hypertension

Endothelial dysfunction is characteristic of patients with essential hypertension, but only limited data are available on different aspects of endothelial function in patients with malignant-phase hypertension. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial damage/dysfunction in patients with previous malignant hypertension (but now in stable phase), who were compared with patients with treated “high-risk” hypertension (hypertension) and healthy controls. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), microvascular (forearm) response to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, circulating endothelial and endothelial progenitor cells in 15 patients with malignant hypertension, 40 matched patients with hypertension, and 40 healthy controls. Patients with malignant hypertension had impaired endothelial-dependant response to acetylcholine (P<0.001, but not to sodium nitroprusside) compared with hypertension and impaired reaction to both stimuli compared with healthy subjects (P<0.001). Patients with malignant hypertension had increased circulating endothelial cells (P=0.001), endothelial progenitors (P=0.008), and stiffness (P=0.003). Both hypertensive groups had impaired response to hyperemia and glyceryl trinitrate when compared with healthy controls (P<0.05). Both hypertensive groups had similar myocardial perfusion, which was significantly lower than in healthy controls. There were no significant differences in hyperemia and endothelium-independent stimuli between the 2 hypertensive groups. In conclusion, despite fairly well-controlled blood pressure, malignant hypertension patients had more pronounced abnormalities of macrovascular and microvascular function (which seem to be both endothelium dependent and endothelium independent) compared with patients with hypertension and healthy controls.

Drug-eluting stents: a comprehensive appraisal

Cardiovascular medicine has evolved over the last few decades, with the advent of percutaneous interventional treatments. In particular, balloon angioplasty and, subsequently, coronary stenting has revolutionized our current perspective of stable and unstable coronary artery disease management. However, the long-term results of stent usage have been blighted by the dual problems of in-stent restenosis and stent thrombosis. Whilst stent thrombosis became much less frequent with the introduction of dual-antiplatelet therapy, restenosis remained a significant problem. Intense work on stent development has successfully led to the introduction of drug-eluting stents (DES) in an effort to address this problem. Randomized trials have consistently proven the superior efficacy of DES over bare metal stents, in elective patients, acute coronary syndromes and patients with diabetes mellitus. Nevertheless, the routine use of DES in by-pass venous graft disease remains debatable. The initial DES used sirolimus and paclitaxel are now being joined by newer stents releasing drugs, such as everolimus, zotarolimus and tacrolimus. Ongoing developments with the stent platform and the polymer coating are also gradually improving the performance of these stents in clinical practice. More recently, the idea of antibody-coated stents that would encourage epithelialization of stent struts by endothelial progenitor cells recruitment has gained attraction among interventionists, with a possible beneficial impact on reducing the incidence of restenosis.

Endothelial Dysfunction: Methods of Assessment & Implications for Cardiovascular Diseases

The endothelium is a thin monocellular layer lining the entire human vascular system, separating blood from interstitium. It plays a core role in the vascular tone by releasing a variety of vasoactive substances, such as nitric oxide (NO) and endothelin. In addition to regulating vasomotion, the healthy endothelium also has anti-thrombotic (through prostacyclins), anti-inflammatory (through developmental endothelial locus-1{Del-1}) and anti-proliferative (through NO and prostaglandin I2) properties. All such mechanisms are regulated by a strict balance amongst several agonist and antagonist biochemical substances secreted by the endothelium. Endothelial dysfunction (ED) is a systemic process in which the endothelium loses the ability/capacity to maintain vascular equilibrium. ED is strongly associated with cardiovascular risk factors/diseases and can be assessed by a number of invasive and non invasive methods. Strict physiological and/or pharmacological management of cardiovascular risk factors improves the functional status of the endothelium and reduces the risk of future cardiac events. This review will provide an overview of the modern perception of endothelial biology, the methods of its assessment and interaction of the endothelium with cardiovascular risk factors and prognosis.

Gender and the response to blood pressure-lowering treatment

Hypertension is a global public health problem, making it one of the leading causes of cardiovascular morbidity and mortality.1,2 The management of hypertension can broadly be divided into the appropriate identification and cardiovascular risk stratification and, secondly, a holistic therapeutic strategy. Given the marked benefits of treating hypertension on complications such as stroke and myocardial infarction, it is no longer a question of ‘do we treat hypertension?’ but the more important questions in relation to hypertension treatment are ‘who to treat?. … and ‘how to treat?’ We know that the prevalence of hypertension is extremely variable in various epidemiological regions of the world. Indeed, ethnic differences in the prevalence of hypertension and its complications are evident, and may influence the approach to cardiovascular prevention.2,3 Furthermore, understanding of genetic, environmental, and biological factors contributing to the development of high blood pressure—as well as responses to drug therapies—could assist in the formulation of primary and secondary prevention programmes. Also, many clinical trials, especially those performed in the last decade, have been conducted to assess the clinical response to various individual and combined antihypertensive regimens. Is gender a major consideration when we choose antihypertensive drugs? The influence of gender differences on cardiovascular disease prevalence, expression, and long-term outcomes has long been the subject of intense research. … *Corresponding author. Tel: +44 121 507 5080; Fax +44 121 507 5907, Email: g.y.h.lip{at}bham.ac.uk

Left Ventricular Systolic and Diastolic Function in Obstructive Sleep ApneaClinical Perspective: Impact of Continuous Positive Airway Pressure Therapy

Background— Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results— A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects ( P <0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness ( P =0.02) and improvement in LV ejection fraction ( P <0.05), systolic S velocity ( P <0.05), and diastolic LV impairment parameters. Conclusions— Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.Background—Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results—A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects (P<0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness (P=0.02) and improvement in LV ejection fraction (P<0.05), systolic S velocity (P<0.05), and diastolic LV impairment parameters. Conclusions—Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.

Left Ventricular Systolic and Diastolic Function in Obstructive Sleep ApneaClinical Perspective

Background— Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results— A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects ( P <0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness ( P =0.02) and improvement in LV ejection fraction ( P <0.05), systolic S velocity ( P <0.05), and diastolic LV impairment parameters. Conclusions— Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.Background—Previous studies in obstructive sleep apnea (OSA) were limited by study cohorts with comorbidities that confound assessment of left ventricular (LV) systolic and diastolic function. We comprehensively evaluated LV function using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3-dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were compared with disease (patients with hypertension, no OSA) and healthy control subjects. Methods and Results—A total of 120 subjects (n=40 each of matched OSA, hypertension and healthy cohorts) underwent echocardiographic examination for the assessment of septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity (S, E′), and left atrial volume index (LAVI). OSA subjects were treated with continuous positive airway pressure (mean duration of 26 weeks), after which the echocardiographic parameters were reassessed. Posterior wall thickness and LV mass index were significantly higher in OSA and hypertensive groups compared with healthy. Systolic S velocity was reduced in OSA and hypertensive compared with healthy control subjects (P<0.05). Diastolic function (E/A, IVRT, and E/E′) was impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly greater in OSA and hypertensive compared with healthy. In OSA patients, continuous positive airway pressure therapy resulted in reduction of the posterior wall thickness (P=0.02) and improvement in LV ejection fraction (P<0.05), systolic S velocity (P<0.05), and diastolic LV impairment parameters. Conclusions—Moderate to severe OSA causes structural and functional changes in LV function and are comparable to that seen in hypertension. These abnormalities significantly improve after CPAP therapy.

Assessment of endothelial function: implications for hypertension and cardiovascular disorders.

Although the endothelium is an integral structural component of the human vascular system, it was, until recently, considered merely as a passive vascular lining separating two interfaces: the blood and the interstitium. Recent advances in cardiovascular biology have confirmed that highly specialized endothelial cells not only secrete several vasoactive substances/ hormones, which maintain vascular hemostasis, but also serve other essential biological functions, such as retardation of smooth muscle proliferation and the modulation of inflammatory cytokines. In simplistic terms, inequilibrium of endothelial hormones is regarded as endothelial dysfunction (ED). However, there still remains some debate as to whether ED is a de novo phenomenon that leads to the future development of cardiovascular disorders or is an intermediary step in the development of cardiac diseases resulting from various inflammatory, autonomic, molecular and biochemical changes. ED has been consistently demonstrated in a wide range of cardiovascular disorders such as hypertension, coronary artery disease (CAD), obstructive sleep apnea and heart failure [1]. Indeed, ED has an important pathophysiological role in the development of cardiovascular disorders. Therefore, it would be fair to say that an accurate assessment of ED would serve as a gauge for the primary prevention of cardiovascular diseases among ‘high risk’ populations, such as those with hypertension (and associated target-organ damage), besides risk stratifying newly diagnosed patients. In hypertension, for example, ED has been linked with complications related to hypertension and an adverse prognosis.