Anna Capra

Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values

Objectives Previous studies have shown that left ventricular hypertrophy (LVH) represents a cardiovascular risk factor independently of clinic blood pressure (BP). The present study was aimed at determining the impact of LVH on the incidence of cardiovascular morbid and fatal events taking into account not only classical risk factors but also home and ambulatory BP values, which have been shown to have an important independent prognostic impact. Methods In 1716 patients belonging to the ‘Pressioni Arteriose Monitorate E Loro Associazioni’ population of Monza, we quantified left ventricular mass index and identified LVH by standard cutoff values. We also measured clinic, home and 24-h ambulatory BPs together with serum glucose and lipids. Results During a follow-up of 148 months, the rate of fatal and nonfatal (hospitalizations) cardiovascular events as well as of all-cause death was markedly greater (four-fold to five-fold) in patients as compared with those without LVH. In LVH individuals, the increased risk remained significant even when data were adjusted for a large number of other confounding factors including home BP, 24-h mean BP and ambulatory BP. Results were similar when left ventricular mass was indexed by height and body surface area. A 10% increase in left ventricular mass index was associated with a significant increase in cardiovascular risk or all-cause deaths. In multivariate analysis, left ventricular mass index was always an independent predictor of cardiovascular events and death for any cause. Conclusion Our data provide evidence that LVH is an important risk factor even when the contribution of different BPs to risk is fully taken into account.

Radial, Carotid and Aortic Distensibility in Congestive Heart Failure: Effects of High-Dose Angiotensin-Converting Enzyme Inhibitor or Low-Dose Association With Angiotensin Type 1 Receptor Blockade

UNLABELLED objectives; The aim of this study was to determine whether in patients with congestive heart failure (CHF) a distensibility (Dist) reduction: 1) similarly occurs in different arteries; 2) is related to CHF severity; and 3) is reversible with treatment. background: Several studies suggest that CHF is accompanied by a reduced arterial Dist. METHODS We measured diameter in radial artery, carotid artery (CA) and abdominal aorta (AO) by echotracking. Distensibility was obtained by relating it to blood pressure. Data were collected in 30 patients with CHF (New York Heart Association functional class I to III) under standard treatment with diuretic, digitalis and angiotensin-converting enzyme (ACE) inhibitor in whom CHF severity was assessed by maximum oxygen consumption (VO(2)max) percentage and in 30 age- and gender-matched controls. Patients with CHF were then randomized to maintain standard treatment (n = 10), double the ACE inhibitor dose (n = 10) or add an angiotensin II antagonist (n = 10) and restudied after two months. RESULTS Distensibility was markedly reduced in the CHF group in all three vessels (p < 0.01), CA and AO Dist being related to CHF severity (p < 0.05). After two months, Dist did not change in the group maintained under standard treatment, but it increased significantly (p < 0.05) and similarly when the ACE inhibitor dose was doubled or an angiotensin II antagonist was added. CONCLUSIONS Congestive heart failure is characterized by a reduction of Dist of large-elastic and middle-sized muscular arteries. The reduction of large-elastic artery Dist is related to the CHF severity. These alterations can be reversed by drugs, effectively interfering with the renin-angiotensin system either at the ACE or at the angiotensin receptor level.

Effects of Heart Rate Changes on Arterial Distensibility in Humans

Abstract—In rats, an increase in heart rate by pacing is accompanied by progressive large-artery stiffening. Whether this is also the case in humans is unknown. We enrolled 20 patients who were chronically implanted with a pacemaker because of atrioventricular block or sick sinus syndrome. Arterial distensibility was measured by an echo-tracking device. In 10 patients, the evaluation was performed on the radial artery by using continuous finger blood pressure measurements, whereas in the remaining 10 patients, the common carotid artery was studied with a semiautomatic measure of brachial artery blood pressure. Diastolic diameter, systodiastolic diameter change, and distensibility were obtained at baseline (heart rate 63±2 beats/min) and after atrial and ventricular sequential pacing at a heart rate of 90 and 110 beats/min. At baseline, the diameter was 7.8±0.3 mm in the carotid artery and 2.4±0.1 mm in the radial artery; the respective systodiastolic diameter change values were 375.4±31.0 and 55.9±9.0 (&mgr;m) and the distensibility values were 1.4±0.1 and 0.7±0.1 (1/mm Hg 10−3). Blood pressure and diameter were not significantly modified by increasing heart rate, which markedly modified systodiastolic diameter change and distensibility. In the radial artery, distensibility was reduced by 47% (P <0.05) at a heart rate of 90 beats/min with no further reduction at 110 beats/min. In the carotid artery, distensibility was reduced by 20% at a heart rate of 90 beats/min (P <0.05) with a further reduction at 110 beats/min (45%, P <0.05). These data provide the first evidence in humans that acute increases in heart rate markedly affect arterial distensibility and that this occurs in both large- and middle-size muscle arteries within the range of “normal” heart rate values.

Acute Effect of High-Fat Meal on Endothelial Function in Moderately Dyslipidemic Subjects

Objective— Hypercholesterolemia markedly impairs endothelial function. Whether this is the case for hypertriglyceridemia is less clear, however, and limited evidence exists on the effect of an acute increase in triglyceridemia caused by a high-fat meal. Methods and Results— In 16 normotensive subjects with an untreated mild hypertriglyceridemia and dyslipidemia and in 7 normal controls, we measured radial artery diameter and blood flow by an echo-tracking device (NIUS02). Data were obtained at baseline, at the release of a 4-minute ischemia of the hand, which causes an increase in arterial diameter dependent on nitric oxide (NO) secretion, and at the release of a 12-minute exclusion of the arm by an arm cuff to obtain a larger increase in arterial diameter mainly of nonendothelial nature. Measurements were performed before and 6 hours after a high-fat meal (680 kcal/m2 body surface; 82% lipids). In mild dyslipidemic hypertriglyceridemic subjects, the high-fat meal did not alter baseline blood pressure (beat-to-beat finger measurement), heart rate, radial artery diameter, and blood flow. It also did not alter the increase in blood flow induced by the 4-minute ischemia (+42.7±10.4 and +43.7±10.4 mL/min), whereas it markedly attenuated the concomitant increase in arterial diameter (+0.31±0.06 versus 0.13±0.06 mm; P<0.05). The alteration of the diameter response did not correlate with changes in total cholesterol, but it showed a significant correlation with the increase in serum triglycerides induced by high-fat meal (r=0.49, P<0.05). This attenuation was not seen in control subjects and in subjects in whom measurements were repeated after a 6-hour observation period. It was also not paralleled by an alteration of the endothelially independent response to a 12-minute ischemia whose larger effects on arterial diameter and blood flow were similar before and after the high-fat meal. Conclusions— Endothelial function is markedly impaired by a high-fat meal that causes an acute hypertriglyceridemia. This impairment is evident in dyslipidemic patients with baseline hypertriglyceridemia but not in normotriglyceridemic controls.

Simultaneous Measurement of Beat-to-Beat Carotid Diameter and Pressure Changes to Assess Arterial Mechanical Properties

Use of local arterial distensibility measurements by change in carotid artery diameter divided by pulse pressure has limitations because blood pressure is often taken in a vessel distant or at a time different from where and when change in diameter is taken. In 92 subjects (23 to 91 years of age), carotid artery diameter was continuously measured ecographically, whereas blood pressure was continuously measured simultaneously tonometrically on the contralateral artery, the 2 signals being synchronized via 2 EKGs. Within each cardiac cycle, there was a linear relationship between the changes in vessel diameter and the changes in blood pressure during either the protomesosystole or the diastole after the dicrotic notch. The diastolic slope was displaced upward and steeper than the systolic slope, the pressure–diameter loop showing a hysteresis. Both slopes showed a high reproducibility when data were averaged over a several-second period. There were small differences between consecutive cardiac cycles, suggesting that modulation of arterial mechanical response to continuous changes in intravascular pressure may undergo physiological variations. In the 92 subjects, systolic and diastolic slopes correlated significantly with distensibility values obtained by Reneman formula and exhibited a close inverse relationship with each subject’s age and systolic blood pressure, thereby showing the ability to reflect age- and pressure-dependent large artery stiffening. This method may allow precise assessment of man’s arterial mechanical properties within each cardiac cycle. This highly dynamic assessment may help to collect information on properties of normal and altered large elastic arteries and the mechanisms involved in disease.

Arterial Stiffening Influence of Sympathetic Nerve Activity Evidence From Hand Transplantation in Humans

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

Increased Arterial Stiffness in Normoglycemic Normotensive Offspring of Type 2 Diabetic Parents

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (−16%), a reduced carotid artery distensibility (−30%), and an increased pulse pressure (+21.8%), all differences being statistically significant (P<0.05) and persisting in subgroups with elevated or normal body mass index values (<25 and ≥25 kg/m2). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.

Relationship between arterial distensibility and coronary atherosclerosis in angina patients.

Objective Arterial stiffening is associated with an increased risk of cardiovascular disease. However, limited evidence exists on whether it also relates to subclinical atherosclerosis, thereby providing a non-invasive marker of the overall cardiovascular status. The aim of the present study was to provide information on arterial stiffening in angina patients in whom angiographic evaluation allowed quantification of coronary atherosclerosis. Methods We studied 101 patients with angina from a large number admitted to our hospital for coronary angiography. In each patient, radial (RA), subdiaphragmatic aorta (AO) and carotid (CA) distensibility (Dist) were measured by an ultrasonic device, following ultrasonic exclusion of atherosclerotic lesions at these specific sites. Patients were classified into three groups according to the angiographic findings: (i) no significant coronary lesions (lumen obstruction < 50%, group A); (ii) one (group B); and (iii) two or three (group C) coronary vessels with hemodynamic significant plaques (lumen obstruction > 50%). Results Age, male prevalence, previous cardiovascular disease and interventions were progressively greater or more common from group A to C, whereas several other risk factors (plasma glucose, serum cholesterol, smoking, history of hypertension, etc.) did not differ between the three groups or between the group with single vessel (B) versus the group with multivessel disease (C). CA and AO Dist decreased progressively from group A to C with a significant relationship in the group as a whole between distensibility values and the number of diseased vessels. The progressive decrease in AO Dist from group A to C remained significant after adjustment for variables that showed between-group differences (such as gender, age and systolic blood pressure) and the ROC curve showed it to be a more sensitive and specific marker of coronary atherosclerosis than CA Dist. RA Dist was similar in the three groups and showed no relationship with the number of diseased vessels in the group as a whole. Conclusion In patients with angina, AO and CA Dist are related to the severity of coronary atherosclerosis, with the relationship being better for alterations in aortic than in carotid mechanical properties. Large elastic artery (and in particular aortic) stiffening can thus be considered as a marker of the severity of coronary atherosclerosis, providing non-invasive obtainable information on the need to proceed with further clinical examinations.

Effects of heart rate changes on arterial distensibility in humans - Response

Effects of Heart Rate Changes on Arterial Distensibility in Humans To the Editor: Dependence of arterial stiffness on heart rate, claimed by Giannattasio et al,1 runs counter to classic studies, which were previously discussed in relation to conflicting data obtained with one method used to measure aortic pulse wave velocity.2 There is a potential flaw in the method applied by Giannattasio et al in their determination of carotid and radial artery distensibility at different heart rates. They measured diameter change of the target artery, but pressure pulsation at a distal site (brachial pressure for carotid, finger pressure for radial artery). Errors inherent in distal pressure measurement have been stressed in a recent consensus document3 but were considered by authors1 to be minimal. We disagree. In similar studies by Wilkinson et al,4 there was an average 35% fall in central pulse pressure, compared with brachial, when heart rate was increased from 60 to 110/min by pacing. Giannattasio et al quoted an early evaluation of the Finapres system and considered this accurate for their purposes, but this study did not test response to change in heart rate. In a later manuscript by the developers of Finapres,5 a marked heart rate difference was noted for systolic pressure between noninvasive finger and brachial intraarterial pressure (20 mm Hg difference for heart rate change of 40 bpm). The differences in distensibility calculated by Giannattasio et al were at the margin of statistical significance (P 0.05). Given the problems in estimating pulse pressure at the site of diameter measurement and the likelihood that this was overestimated, we continue to rely on the previous work,2,3 which showed no significant dependence of arterial stiffness on heart rate.

Low anthracyclines doses-induced cardiotoxicity in acute lymphoblastic leukemia long-term female survivors†

High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long‐term survivors of ALL.