Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

[1]  E. Picano,et al.  Coronary microvascular disease in hypertensives. , 1992, Clinical and experimental hypertension. Part A, Theory and practice.

[2]  R. Cannon Chest pain with normal coronary angiograms: is the heart innocent or guilty? , 1990, Journal of the American College of Cardiology.

[3]  J. Kaski,et al.  Rarefaction of skin capillaries in patients with anginal chest pain and normal coronary arteriograms. , 2001, European heart journal.

[4]  N. D. De Cesare,et al.  Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest. , 1991, The American journal of cardiology.

[5]  A. Gearing,et al.  Circulating adhesion molecules in disease. , 1993, Immunology today.

[6]  P A Poole-Wilson,et al.  Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. , 1995, Journal of the American College of Cardiology.

[7]  N. Markandu,et al.  Structural skin capillary rarefaction in essential hypertension. , 1999, Hypertension.

[8]  P. Ponikowski,et al.  Abnormal autonomic control of the cardiovascular system in syndrome X. , 1994, The American journal of cardiology.

[9]  E. Ferrannini,et al.  Coronary hemodynamics and myocardial metabolism in patients with syndrome X: response to pacing stress. , 1991, Journal of the American College of Cardiology.

[10]  R. Kronmal,et al.  Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. , 1986, Journal of the American College of Cardiology.

[11]  N. Reichek,et al.  Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. , 2000, The New England journal of medicine.

[12]  A. Takeshita,et al.  Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. , 1993, The New England journal of medicine.

[13]  T. Katagiri,et al.  Ultrastructural changes of blood capillaries in patients with microvascular angina, hypertrophic cardiomyopathy, and dilated cardiomyopathy. , 1995, The American journal of cardiovascular pathology.

[14]  S. Fichtlscherer,et al.  Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease , 2000, Circulation.

[15]  Peter S. Mortimer,et al.  Capillary rarefaction in the forearm skin in essential hypertension , 1995, Journal of hypertension.

[16]  A. Quyyumi,et al.  Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. , 1990, Journal of the American College of Cardiology.

[17]  A. Blann,et al.  von Willebrand Factor, Soluble P-Selectin, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor in Atherosclerosis , 1995, Thrombosis and Haemostasis.

[18]  A. Palazzuoli,et al.  Dyslipidemias and fibrinolysis. , 2002, Italian heart journal : official journal of the Italian Federation of Cardiology.

[19]  M. Mulvany,et al.  Reduced vasodilator capacity in syndrome X related to structure and function of resistance arteries. , 1999, The American journal of cardiology.

[20]  E F Ring,et al.  Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls. , 1996, Annals of the rheumatic diseases.

[21]  P. Marraccini,et al.  Forearm vasodilatory capacity in patients with syndrome X: a comparison with normal and hypertensive subjects. , 1989, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[22]  D. Nassiri,et al.  Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. , 2003, European heart journal.

[23]  G. Desideri,et al.  Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. , 1998, Diabetes.

[24]  W. Kübler,et al.  Reduced Coronary Dilatory Capacity and Ultrastructural Changes of the Myocardium in Patients with Angina Pectoris But Normal Coronary Arteriograms , 1981, Circulation.

[25]  R. Cannon,et al.  "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. , 1988, The American journal of cardiology.

[26]  R. Cannon,et al.  Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? , 1987, The New England journal of medicine.

[27]  H. Bøtker,et al.  Frequency of systemic microvascular dysfunction in syndrome X and in variant angina. , 1996, The American journal of cardiology.

[28]  M. Gotsman,et al.  Histologic evidence for small-vessel coronary artery disease in patients with angina pectoris and patent large coronary arteries. , 1986, Circulation.

[29]  K. Gomi,et al.  Elevated complement activities of sera from patients with high density lipoprotein deficiency (Tangier disease): the presence of normal level of clusterin and the possible implication in the atherosclerosis , 1993, Clinical and experimental immunology.

[30]  James T. Willerson,et al.  Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells , 2000, Circulation.

[31]  J. Leddy,et al.  Inhibition of the lytic action of cell-bound terminal complement components by human high density lipoproteins and apoproteins. , 1983, The Journal of clinical investigation.

[32]  N. Markandu,et al.  Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests. , 1999, Clinical science.

[33]  A. Palazzuoli,et al.  Relationship between serum complement and different lipid disorders , 2002, Clinical and Experimental Medicine.

[34]  F. Bühler,et al.  Nailfold microcirculation in normotensive and essential hypertensive subjects, as assessed by video-microscopy , 1992, Journal of hypertension.

[35]  H. Kemp Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. , 1973, The American journal of cardiology.

[36]  P. Puddu,et al.  Vasotonic angina: a spectrum of ischemic syndromes involving functional abnormalities of the epicardial and microvascular coronary circulation. , 1993, Journal of the American College of Cardiology.

[37]  N. Markandu,et al.  Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. , 1999, Hypertension.

[38]  C. Cimminiello,et al.  Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol. , 1997, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.