Transthoracic echocardiographic abnormalities in asymptomatic diabetic patients: association with microalbuminuria and silent coronary artery disease.

AIMS: This study aimed to assess, on routine echocardiography, cardiac left ventricular (LV) disorders, their determinants and their role in the screening process of silent myocardial ischaemia (SMI) in asymptomatic diabetic patients. METHODS: A total of 586 asymptomatic diabetic patients with one or more additional cardiovascular risk factors, but no history of heart failure or myocardial infarction, prospectively underwent rest echocardiography and myocardial scintigraphy. Those with SMI (abnormal scintigraphy) were subsequently screened for angiographic coronary artery disease (CAD). RESULTS: LV hypertrophy, LV dilatation, systolic dysfunction and hypokinesia were found in 33.6, 8.6, 3.2 and 6.1%, respectively, of the study population. SMI was found in 156 (26.6%) patients, 55 of whom had silent CAD. On multivariate analysis, age (OR: 1.03 [1.00-1.05], P=0.02), microalbuminuria (OR: 2.2 [1.4-3.2], P<0.0001) and silent CAD (OR: 2.4 [1.3-4.6], P=0.007) were predictive of LV hypertrophy. Creatinine clearance (OR: 0.97 [0.96-0.99], P=0.002) and silent CAD (OR: 3.7 [1.3-10.0]) were associated with LV dilatation. LV systolic dysfunction was associated with microalbuminuria (OR: 3.8 [1.3-11.4], P=0.02) and silent CAD (OR: 3.8 [1.1-12.6], P=0.03). Hypokinesia was associated with retinopathy (OR: 2.4 [1.1-5.4], P=0.04), microalbuminuria (OR: 2.3 [1.1-5.0], P=0.04) and LV dilatation (OR: 3.0 [1.1-8.1], P=0.03). In patients with SMI, the positive predictive value of LV hypertrophy associated with another echocardiographic abnormality (n=19) for CAD was 63.2%. CONCLUSION: LV hypertrophy was found in one-third of asymptomatic diabetic patients, while LV dilatation, systolic dysfunction or hypokinesia was seen in<10%. The main predictors of LV abnormalities were microalbuminuria and silent CAD. The presence of LV hypertrophy with another abnormality should raise the possibility of the presence of silent CAD.

N-terminal pro-B-type natriuretic peptide: an independent marker for coronary artery disease in asymptomatic diabetic patients.

AIMS: To determine whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a marker for cardiac failure and potentially for the severity of coronary artery disease (CAD), predicts silent myocardial ischaemia (SMI) and silent CAD in asymptomatic high-risk diabetic patients. METHODS: Five hundred and seventeen asymptomatic diabetic patients with > or = 1 additional cardiovascular risk factor but without heart failure were prospectively screened between 1998 and 2008 for SMI, defined as an abnormal stress myocardial scintigraphy, and subsequently for significant (> 70%) angiographic CAD. The 323 patients with interpretable echocardiography and for whom NT-proBNP was measured were included in this analysis. RESULTS: SMI was found in 108 (33.4%) patients, 39 of whom had CAD. NT-proBNP was higher in the patients with CAD than in the patients without CAD [45.0 (1-3199) vs. 20.0 (1-1640) pg/ml; P < 0.0001 median (range)], even after adjustment for confounding factors: age, gender, body mass index, glycated haemoglobin (HbA(1c)), retinopathy, nephropathy, hypertension, echocardiographic parameters (P < 0.05). NT-proBNP in the third tertile (> or = 38 pg/ml) predicted CAD with a sensitivity of 59% and a specificity of 67%. In a multiple logistic regression analysis including NT-proBNP > or = 38 pg/ml, age, body mass index, gender, HbA(1c), hypertension, retinopathy, nephropathy, peripheral occlusive arterial disease, left ventricular systolic dysfunction, dilatation and hypertrophy and Type 1 transmitral flow, NT-proBNP > or = 38 pg/ml was the only significant independent predictor of silent CAD [odds ratio (OR) 3.1 (95% confidence interval 1.3-7.6), P = 0.015]. CONCLUSIONS: NT-proBNP measurement helps to better define asymptomatic diabetic patients with an increased likelihood for CAD, independently of cardiac function and structure.

[Microalbuminuria and urinary albumin excretion: French guidelines]. / Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique.

UNLABELLED: Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: in patients with microalbuminuria, weight reduction, sodium restriction (< 6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines.

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

[Hypertension, endothelial dysfunction and cardiovascular risk]. / Hypertension artérielle, dysfonction endothéliale et risque cardiovasculaire.

Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.

Postprandial endothelial dysfunction: role of glucose, lipids and insulin.

Endothelium plays a key role in the regulation of vascular tone and development of atherosclerosis. Endothelial function is impaired early in patients with risk factors and endothelial dysfunction is a strong and independent predictor of cardiovascular events. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meals, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. Experimental and human studies have shown that a transient increase of blood concentrations of glucose, triglycerides and fatty acids, and insulin are able to depress endothelium-dependent vasodilation in healthy subjects and that hyperglycemia, hypertriglyceridemia and hyperinsulinemia are generator of reactive oxygen species at the origin of a cascade of pathophysiological events resulting in the activation of nuclear factor-kappaB. Nuclear factor-kappaB is an ubiquitous transcription factor controlling the expression of numerous genes and is involved in immunity, inflammation, regulation of cell proliferation and growth and apoptosis. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress.

[Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment]. / Dysfonction endothéliale chez les patients diabétiques. Mise en évidence, potentiel pathogène, quels traitements?

Cardiovascular diseases are the leading cause of morbidity and mortality in people with diabetes. Vascular abnormalities can be observed long before atherosclerosis develops and in sites not usually prone to atherosclerosis. These vascular abnormalities are known to be due to endothelial dysfunctions, one of the most frequent of which is depressed endothelium-dependent dilation. In patients with diabetes, this is mainly linked to decreased bioavailability of nitric oxide. Although inactivation of tetrahydrobiopterin, a co-factor of NO-synthase, may depress nitric oxide production, the latter is more likely due to the inactivation of nitric oxide by superoxide anions: enhanced oxidative stress increases their production in people with diabetes. Moreover, hyperglycemia directly activates oxidative stress, which in turn depresses endothelium-dependent vasodilation. Glycemia and oxidative stress are positively correlated in people with diabetes. However, while depression of endothelium-dependent dilation may be a visible functional manifestation of oxidative stress, the oxidative stress itself is mainly responsible for the cascade of endothelial events that play a key role in development of vascular atherosclerosis and its complications. Especially important among these events are the activation of NF-kappaB and the oxidation of LDL-cholesterol. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes.

[Physiopathology of coronary microcirculation]. / Physiopathologie microcirculatoire.

Coronary microcirculatory is the main target of contrast echocardiography. Coronary flow is one of the parameters which influence the myocardial blood flow but not the only one. Therefore, the knowledge of microcirculatory physiopathology is required in order to analyze datas from contrast echo.

[Vascular endothelium: a target organ for diabetes mellitus]. / L'endothélium vasculaire: un organe cible du diabète.

Diabetes mellitus is responsible for abnormalities in the control of endothelium-dependent vascular reactivity observed on both coronary arteries and coronary microvessels. These abnormalities of coronary artery circulation are associated with structural microcirculatory abnormalities even in subjects with angiographically normal coronary arteries. Both these structural and functional abnormalities might be responsible for an inadequate coronary response to an increased myocardial metabolic demand. These could be a key factor in the progressive myocardial alterations and in the physiopathology of diabetic cardiomyopathy. Their role in the genesis of arterial hypertension in diabetic patients remain to be clarified. The main physiopathological mechanisms of endothelial dysfunction are reviewed.

[Inhibition of iron-catalyzed oxidative reactions restores mathcing between coronary blood flow and myocardial metabolic demand in type 2 diabetes]. / L'inhibition des réactions oxydantes catalysées par le fer rétablit l'adaptation du débit coronaire à la demande métabolique du myocarde chez les diabétiques de type 2.

In diabetes, endothelium-dependent dilation of large and small coronary arteries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an iron chelator that inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold pressor test and flow increase in angiographically normal epicardial coronary arteries of diabetic patients. This result suggests that nitric oxide could be inactivated by reactive oxygen species. The aim of this study was to assess the effects of deferoxamine on coronary microcirculation vasomotion when myocardial oxygen demand is increased by sympathetic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without any other coronary risk factors, coronary blood flow has been measured using quantitative angiography and intracoronary Doppler at baseline and during a cold pressor test, before and after intravenous administration of 500 mg deferoxamine. Increase in rate-pressure product, an estimate of myocardial metabolic demand, was similar before and after deferoxamine (+21.1 +/- 8.7% vs +20.5 +/- 8.9%, respectively), but coronary blood flow increase was significantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%, respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation between coronary blood flow and rate-pressure product changes before deferoxamine (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary microcirculation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matching between myocardial oxygen demand and coronary blood flow.

Impairment of coronary microvascular dilation in response to cold pressor--induced sympathetic stimulation in type 2 diabetic patients with abnormal stress thallium imaging.

Coronary microcirculation dysfunction may be associated with myocardial perfusion defects on thallium imaging in diabetic patients without coronary artery stenosis. Microvascular coronary adaptation to increased myocardial oxygen demand in response to sympathetic stimulation evoked by the cold pressor test was examined in 22 type 2 diabetic patients with thallium imaging defects and in 15 control subjects. Both the diabetic patients and control subjects had angiographically normal coronary arteries and no other risk factors. Despite a similar increase in the rate-pressure product in the two groups (22.6 +/- 12.4% in diabetic patients and 31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in the left anterior descending artery (mean flow velocity measured by intracoronary Doppler multiplied by the cross-sectional area measured by digital angiography) was significantly lower in diabetic patients than in control subjects (14.7 +/- 19.8 vs. 75.5 +/- 13.5%, respectively; P = 0.0001). In addition, when there was a positive correlation between the two parameters in control subjects (r = 0.651, P < 0.01), there was no relationship in diabetic patients (r = 0.054). In conclusion, vasodilation of the coronary microcirculation in response to sympathetic stimulation evoked by the cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilation during current life stress episodes such as exercise, mental stress, or cold exposition.

Left ventricular mechanical efficiency in hypertensive patients with and without increased myocardial mass and with normal pump function.

Left ventricular hypertrophy (LVH) is a physiologic process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular contractile performance, mechanical efficiency and ventriculoarterial coupling are preserved in hypertensive patients with LVH. To assess the differences between patients with and without LVH, left ventricular contractile performance and the ventriculoarterial coupling were compared in two groups of hypertensive patients with similar body surface area and arterial pressures, and normal pump function: 30 patients with LVH (group 1) and 23 without LVH (group 2). Left ventricular angiography coupled with simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and pressure-volume area (PVA). Myocardial contractile performance, assessed by Ees normalized by myocardial mass and by ESSVR, was lower in group I than in group 2 (1.23 +/- 0.28 v 1.89 +/- 0.48 mm Hg/mL/100 g, and 3.85 +/- 0.99 v 5.13 +/- 0.56 g/cm2/mL, respectively, both P < .001). Ventriculoarterial coupling evaluated through Ea/Ees ratio, and mechanical efficiency evaluated through EW/PVA ratio, were similar in the two groups (0.53 +/- 0.08 v 0.51 +/- 0.05, and 0.78 +/- 0.03 v 0.80 +/- 0.02, respectively, NS). In conclusion, this study shows that ventriculoarterial coupling and mechanical efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in hypertensive patients, the matching between left ventricular performance and arterial load and the energy transfer are preserved either through left ventricular hypertrophy with moderate depression of myocardial contractile performance or through enhancement of myocardial contractile performance in patients with normal left ventricular mass.

Restoration of flow-dependent coronary dilation by ACE inhibition improves papaverine-induced maximal coronary blood flow in hypertensive patients: demonstration that large epicardial coronary arteries are more than conductance vessels.

Restoration of flow-dependent coronary artery dilation by angiotensin-converting enzyme inhibition (ACEI) has been demonstrated in patients with hypertension. The aim of the present study was to evaluate whether dilation of conductance coronary arteries may alter maximal coronary blood flow (CBFmax) and minimal coronary resistance (CRmin) in hypertensive patients with reversible impairment of flow-dependent coronary artery dilation. Thirteen hypertensive patients with angiographically normal coronary arteries and no other risk factors were studied. Cross-sectional areas (CSAs) of proximal and distal left anterior descending (LAD) coronary arteries were determined by quantitative angiography. Coronary flow velocity was recorded in the distal LAD with an intracoronary Doppler catheter. Estimates of coronary blood flow and resistance were calculated at rest and during maximal increase in blood flow induced by papaverine injected in the midportion of the LAD, both before and after ACEI. Flow-dependent dilation of the proximal LAD, abolished before ACEI, was restored after (26.7 +/- 11.2%; p < 0.001). The increase in CSA of the distal LAD exposed to papaverine was significantly higher after ACEI than before (from 33.4 +/- 20.5% to 51.5 +/- 23.4%; p < 0.001). After restoration of proximal LAD flow-dependent dilation, CBFmax was increased by +21.0 +/- 10.3% (p < 0.001), and CRmin was reduced by 19.3 +/- 9.5% (p < 0.001). Thus, dilation of epicardial coronary arteries participates substantially in the coronary resistance in hypertensive patients. Restoration of flow-dependent coronary artery dilation by ACEI may improve the ability of coronary circulation to deliver its maximal myocardial blood flow in hypertensive patients.

[Dysfunction of the coronary microcirculation in type 2 diabetic patients]. / Dysfonction de la microcirculation coronaire chez les diabétiques de type 2.

A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.

Short-term variability of pulse pressure and systolic and diastolic time in heart transplant recipients.

In heart transplant recipients (HTR), short-term systolic blood pressure variability is preserved, whereas heart rate variability is almost abolished. Heart period is the sum of left ventricular ejection time (LVET) and diastolic time (DT). In the present time-domain prospective study, we tested the hypothesis that short-term fluctuations in aortic pulse pressure (PP) in HTR were related to fluctuations in LVET. Seventeen male HTR (age 48 +/- 6 yr) were studied 16 +/- 11 mo after transplantation. Aortic root pressure was obtained over a 15-s period using a micromanometer both at rest (n = 17) and following the cold pressor test (CPT, n = 14). There was a strong positive linear relationship between beat-to-beat LVET and beat-to-beat PP in all patients at rest and in 13 of 14 patients following CPT (each P < 0.01). The slope of this relationship showed little scatter both at rest (0.34 +/- 0.07 mmHg/ms) and following CPT (0.35 +/- 0.09 mmHg/ms, P = not significant). Given the essentially fixed heart period, DT varied inversely with LVET. As a result, in 13 of 17 HTR at rest and in 12 of 14 HTR following CPT, there was a negative linear relationship between beat-to-beat PP and DT. In conclusion, our short-term time-domain study demonstrated a strong positive linear relationship between LVET and blood pressure variability in male HTR. We also identified a subgroup of HTR in whom there was a mismatch between PP and DT.

Effects of nicotine gum on coronary vasomotor responses during sympathetic stimulation in patients with coronary artery stenosis.

Smoking-cessation rates may be improved by nicotine-replacement therapy that reduces withdrawal symptoms. However, nicotine may have adverse effects on coronary circulation. The purpose of this study was to examine the short-term effects of nicotine gum chewing on the dimensions of coronary arteries of patients with coronary artery disease and on the response of coronary vessels to sympathetic stimulation caused by the cold pressor test. In 17 patients who were past chronic cigarette smokers, cross-sectional areas of 32 coronary artery stenoses and 32 adjacent apparently normal segments were measured by using quantitative coronary angiography at baseline and after a cold pressor test before and after nicotine gum chewing. The cold pressor test produces an increase in arterial pressure without any change in heart rate. These changes were similar before and after nicotine gum. Before nicotine gum, the cross-sectional area of coronary stenoses and apparently normal segments was significantly and similarly reduced during the cold pressor test (-11+/-12% and -11+/-12%, respectively; both p values <0.0001 vs. baseline). After nicotine gum, baseline cross-sectional area was not modified, and response to the cold pressor test was similar to that observed before nicotine gum (-11+/-18% and -12+/-12%, respectively; both p values <0.0001 vs. baseline). In conclusion, nicotine-replacement therapy by using nicotine gum does not reduce the surface area of normal and diseased coronary segments and does not enhance the constricting effect of sympathetic stimulation produced by the cold pressor test. Thus nicotine gum may be considered a relatively safe drug in patients who need nicotine-replacement therapy to stop smoking.

[Left ventricular performance, ventriculo-arterial coupling and mechanical output in hypertensive patients with and without left ventricular hypertrophy]. / Performance ventriculaire gauche, couplage ventriculo-artériel et rendement mécanique chez les sujets hypertendus avec et sans hypertrophie ventriculaire gauche.

Left ventricular hypertrophy (LVH) is a physiological process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular (LV) contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with LVH. To assess the differences between patients with and without LVH, LV contractile performance, the ventriculoarterial coupling and mechanical efficiency were compared in 2 groups of hypertensive patients with similar body surface area and arterial pressures, 23 without LVH (group 1) and 30 with LVH (group 2) and compared to data of 20 normotensive subjects. Left ventricular angiography coupled with simultaneous recording of pressures with micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW) and pressure-volume area (PVA). Left ventricular contractile performance assessed by Ees/100 g myocardial mass and EESVR were lower in group 2 than in group 1 (1.23 +/- 0.28 vs 1.89 +/- 0.48 mmHg/mL/100 g and 6.22 +/- 1.07 vs 9.56 +/- 0.97 g/cm2/mL/m2, respectively, both p < 0.0001, control subjects: 1.47 +/- 0.41 and 6.97 +/- 1.22, respectively). Ventriculoarterial coupling evaluated through Ea/Ees ratio (0.51 +/- 0.05 in group 1 vs 0.53 +/- 0.08 in group 2, 0.49 +/- 0.09 in control subjects), and work efficiency evaluated through EW/PVA ratio (0.80 +/- 0.02 in group 1 vs 0.78 +/- 0.03 in group 2, 0.80 +/- 0.03 in control subjects), were similar in the 2 groups and were comparable to control subject values. In conclusion, this study shows that ventriculoarterial coupling and work efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in patients without LVH the matching between left ventricle and arterial receptor is preserved through an enhancement of myocardial contractility which is energetically costly. Conversely, LVH seems to be a useful adaptation which minimizes the energetical cost of high pressure generation.

Determinants of echocardiographically measured left ventricular mass in diabetic patients with or without silent myocardial ischaemia.

Left ventricular hypertrophy (LVH) is a recognized independent risk factor for cardiovascular morbidity and mortality. The purpose of this study was to assess the determinants of left ventricular mass index (LVMI), according to the presence or absence of silent myocardial ischaemia (SMI), in diabetic patients with at least two additional risk factors but with no known coronary artery disease. Eighty diabetic patients (14 Type 1 and 66 Type 2) were studied, and LVMI was measured echocardiographically. Three non-invasive tests (the ECG stress test, thallium-201 myocardial scintigraphy with intravenous dipyridamole infusion, and ambulatory 48-h ECG monitoring) were performed on all patients. Forty-five percent of patients had LVH (LVMI > or = 110 g/m2 in men and > or = 106 g/m2 in women). Twenty-six patients (37%) had SMI assessed on at least one of the non-invasive tests, 7 of whom had significant coronary stenoses on angiography. LVMI was significantly higher in patients with coronary stenoses on angiography than in those with SMI but without coronary stenoses or in those without SMI (p < 0.05), and was correlated with systolic blood pressure. In patients free of SMI, LVMI correlated with creatininemia. In patients with SMI and normal coronary arteries on angiography, LVMI correlated with the waist/hip girth ratio, the log urinary albumin excretion rate and the red blood cell filtration index (a rigidity index). This study suggests that LVH is very frequent in diabetic patients and that the main factor contributing to the increase of LVMI differs according to the presence or absence of SMI and coronary stenoses: volume load in patients free of SMI, microcirculatory disorders in those with SMI but with normal coronary arteries, and blood pressure in those with coronary stenoses.

Left ventricular contractile performance, ventriculoarterial coupling, and left ventricular efficiency in hypertensive patients with left ventricular hypertrophy.

Contractile performance of hypertrophied left ventricle may be depressed in arterial hypertension. Ventriculoarterial coupling is impaired when myocardial contractile performance is reduced and when afterload is increased. The left ventricular contractile performance and the ventriculoarterial coupling were evaluated in 30 hypertensive patients with moderate left ventricular hypertrophy and 20 control subjects. Left ventricular angiography coupled with the simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress/volume index, the slope of end-systolic pressure-volume relationship, ie, end-systolic elastance, effective arterial elastance, external work, and pressure-volume area. In hypertensive patients, left ventricular contractile performance, as assessed by end-systolic elastance/ 100 g myocardial mass, was depressed (4.35 +/- 1.13 v 5.21 +/- 1.89 mm Hg/mL/100 g in control subjects P < .02), when end-systolic stress-to-volume ratio was comparable in the two groups (3.85 +/- 0.99 g/cm2/mL in hypertensive patients versus 3.51 +/- 0.77 g/cm2/mL in control subjects). Ventriculoarterial coupling, evaluated through effective arterial elastance/end-systolic elastance ratio, was slightly higher in hypertensive patients (0.53 +/- 0.08 v 0.48 +/- 0.09 mm Hg/mL in control subjects, P < .05), and work efficiency (external work/pressure-volume area) was similar in the two groups (0.78 +/- 0.04 mm Hg/mL in hypertensive patients versus 0.80 +/- 0.03 mm Hg/mL in control subjects). This study shows that despite a slight depression of left ventricular contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with left ventricular hypertrophy. Thus, it appears that left ventricular hypertrophy might be a useful means of preserving the match between left ventricle and arterial receptor with minimal energy cost.