Quality of care and clinical inertia in the management of cardiovascular risk factors in patients with type 1 and type 2 diabetes: data from AMD annals.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view.

BACKGROUND:  Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE:  The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.

The quality of care in type 1 and type 2 diabetes - A 2023 update of the AMD Annals initiative.

AIMS: An initiative of continuous monitoring of the quality of diabetes care, promoted by the Association of Medical Diabetologists, is in place in Italy since 2006 (AMD Annals). The initiative was effective in improving quality of care indicators, assessed periodically through standardized measures. Here, we show the 2023 AMD Annals data on type 2 (T2D) and type 1 (T1D) diabetes. METHODS: A network of over 1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic medical records, using a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. RESULTS: 296 centers provided data on 573,164 T2D (mean age 69.7 ± 11.2 years) and 42,611 T1D subjects (mean age 48.6 ± 16.9 years). A HbA1c value ≤ 7.0 % was documented in 56.3 % of patients with T2D and 35.9 % of those with T1D. Only 6.6 % of T2D patients and 3.5 % of those with T1D reached the composite outcome of HbA1c ≤ 7.0 % + LDL-C < 70 mg/dl + BP < 130/80 mmHg. Notably, only 2.8 % and 3.2 % of T2D and T1D patients, respectively, showed a Q score < 15, which correlates with an 80 % higher risk of incident CVD events compared to scores > 25. CONCLUSIONS: We documented an overall good quality of care in both T1D and T2D subjects. However, the failure to achieve the targets of the main risk factors, especially if combined, in a still too large proportion of patients testify the difficulty to apply the more and more stringent indications recommended by guidelines in the everyday clinical practice.

Which patients should be evaluated for blood glucose variability?

Diabetes is characterized by glycaemic disorders that include both sustained chronic hyperglycaemia and acute fluctuations (i.e. glycaemic variability). Increasing attention is being paid to the role of glycaemic variability as a relevant determinant for diabetes control and prevention of its vascular complications. As a consequence, it is strongly suggested that a global antidiabetic strategy should be aimed at reducing to a minimum the different components of glycaemic control (i.e. HbA1c, fasting and postprandial glucose, as well as glycaemic variability). Subjects at risk of hypoglycaemia, subjects with postprandial hyperglycaemia and patients who need to adjust or start insulin seem to be the categories that require glycaemic variability monitoring. The analysis of blood glucose variability represents an additional tool in the global assessment of glycaemic control and can serve as a guide to the clinician in the management of therapy and for the patients both in the prevention of acute complications, in particular hypoglycaemia, and chronic disease, in particular macrovascular complications.

How can we monitor glycaemic variability in the clinical setting?

No universal consensus exists on how to express glycaemic variability. Among other parameters, standard deviation of blood glucose values, mean amplitude of glycaemic excursions (MAGE), the Low Blood Glucose Index (LBGI) and the High Blood Glucose Index (HBGI), which were subsequently combined into the Average Daily Risk Range (ADRR), mean of daily differences (MODD) and glycaemic variability index (GVI) are highlighted. The continuous glucose monitoring in research and clinical settings has been a great help for a comprehensive approach to circadian blood glucose evaluation and identification of individual patterns, mainly in type 1 diabetes, but recently also in type 2 diabetes. In everyday clinical practice the judicious use of self-monitoring of blood glucose in an educational setting involving the patient and the care team is an unreplaceable tool to effectively and safely guide behavioural and drug therapy.

The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. METHODS AND RESULTS: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S' (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care.

AIMS: Since 2006, the Italian AMD (Associations of Medical Diabetologists) Annals Initiative promoted a continuous monitoring of the quality of diabetes care, that was effective in improving process, treatment and outcome indicators through a periodic assessment of standardized measures. Here, we show the 2022 AMD Annals data on type 2 diabetes (T2D). METHODS: A network involving ∼1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic clinical records, by a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. RESULTS: 295 centers provided the annual sample of 502,747 T2D patients. Overall, HbA1c value ≤7.0% was documented in 54.6% of patients, blood pressure <130/80 mmHg in 23.0%, and LDL-cholesterol levels <70 mg/dl in 34.3%, but only 5.2% were at- target for all the risk factors. As for innovative drugs, 29.0% of patients were on SGLT2-i, and 27.5% on GLP1-RAs. In particular, 59.7% were treated with either GLP1-RAs or SGLT2-i among those with established cardiovascular disease (CVD), 26.6% and 49.3% with SGLT2-i among those with impaired renal function and heart failure, respectively. Notably, only 3.2% of T2D patients showed a Q score <15, which correlates with a 80% higher risk of incident CVD events compared to scores >25. CONCLUSIONS: The 2022 AMD Annals data show an improvement in the use of innovative drugs and in the overall quality of T2D care in everyday clinical practice. However, additional efforts are needed to reach the recommended targets for HbA1c and major CVD risk factors.

Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review.

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.

Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14.

AIMS: To determine the ability of probiotic lactobacilli to improve the treatment of vulvovaginal candidiasis (VVC) using a randomized, double-blind and placebo-controlled trial. METHODS AND RESULTS: Fifty-five women diagnosed with VVC by vaginal discharge positive for Candida spp. (according to culture method) associated with at least one of the symptoms (itching and burning vaginal feeling, dyspareunia and dysuria), were treated with single dose of fluconazole (150 mg) supplemented every morning for the following 4 weeks with two placebo or two probiotic capsules (containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14). At 4 weeks, the probiotic treated group showed significantly less vaginal discharge associated with any of the above mentioned symptoms (10.3%vs 34.6%; P = 0.03) and lower presence of yeast detected by culture (10.3%vs 38.5%; P = 0.014). CONCLUSION: This study has shown that probiotic lactobacilli can increase the effectiveness of an anti-fungal pharmaceutical agent in curing disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel finding of probiotic lactobacilli augmenting the cure rate of yeast vaginitis, not only offers an alternative approach to a highly prevalent condition that adversely affects the quality of life of women around the world, but also raises the question of how this combination works.

Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy.

AIM: Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. METHODS: LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. RESULTS: The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. CONCLUSION: Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model.

Predictors of treatment response to liraglutide in type 2 diabetes in a real-world setting.

AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. RESULTS: Data from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90-4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as - 2.2% (24 mol/mol) in the former versus - 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Characterization and application of cellulose acetate synthesized from sugarcane bagasse.

The synthesis and application of cellulose acetate (CA) from sugarcane bagasse were investigated. Firstly, cellulose was extracted by a sequential treatment with H2SO4 (10% v/v), NaOH (5% w/v), EDTA (0.5% w/V), and H2O2 (5% v/v), and characterized by X-ray diffraction (DRX). After the acetylation of the extracted cellulose, CA was characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetry analysis (TGA), and was applied in the membrane production. The membranes were analyzed by DSC and atomic force microscopy (AFM), and tested in the flux of water vapor to determinate the best conditions for membrane manufacturing. FTIR analysis proved the replacement of free OH groups by acetyl groups, and the thermal analysis showed that sugarcane bagasse CA possessed thermal properties compared to commercial grade CA. The best conditions to prepare membrane were: 3% (w/v) of polymer/solvent relation, 10min of solvent evaporation time, and 20°C as temperature for the coagulation bath. These results show that CA can be successfully synthesized from sugarcane bagasse and applied in membrane preparation.

Synthesis of cellulose acetate and carboxymethylcellulose from sugarcane straw.

Sugarcane straw (SCS) is a raw material with high potential for production of cellulose derivatives due to its morphology and structure. The proposal of this work was to synthesize cellulose acetate (CA) and carboxymethylcellulose (CMC) from sugarcane straw cellulose, and applied the CA in the preparation of a membrane. The cellulose extraction was carried out in four steps. Firstly, SCS was treated with H2SO4 (10% v/v) followed by NaOH (5% w/v) treatment. Subsequently, a chelating process was performed before ending the extraction process with chemical bleaching using H2O2 (5% v/v). The extracted cellulose was employed in the obtainment of CA and CMC. The CA presented a degree of substitution (DS) of 2.72. Its FTIR spectrum showed that practically all hydroxyl groups were replaced by acetate groups. The membrane synthesized from CA was dense and homogeneous. The presence of small particles on the top and bottom surfaces decreased the mechanical resistance of the membrane. The CMC presented a low DS (0.4) demonstrating the carboxymethylation reaction was not very effective due to the presence of lignin. These results proved that SCS can be utilized in the synthesis of CA and CMC.

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

Contribution of systemic blood pressure to myocardial remodeling in uremic rats.

Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Group 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant (P < .01) increase in left ventricular weight (2.45 +/- 0.1 and 2.5 +/- 0.5 mg/g body wt, respectively) compared with group 2 (1.9 +/- 0.06 mg/g body wt). Cardiac hydroxyporline concentration was also lower in group 2 compared with group 1 (2.07 +/- 0.16 versus 2.73 +/- 0.17 mg/g left ventricular weight, P < .05) but not compared with group 3 (2.59 +/- 0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme inhibition on left ventricular mass and intracardiac collagen content appeared to be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a close relationship between systolic pressure and left ventricular mass; however, no relationship between the degree of cardiac fibrosis and systolic pressure could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage in hypertensive diabetic rats.

OBJECTIVE: Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats. DESIGN AND METHODS: Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated. RESULTS: The blood pressure reduction was equal in rats receiving either SPI or HRH. The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis. CONCLUSIONS: The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis.

Regional and systemic haemodynamic response to aortography in hypertensives.

OBJECTIVE: To study the effects of aortography and of aortic counterflow bolus injection per se on regional and systemic haemodynamics in hypertensives in comparison to normotensive matched controls. DESIGN AND METHODS: Mean blood velocity (MBV) and pulsatility index (PI)--as an index of regional vascular resistance--by the Doppler technique, at the femoral, common carotid and brachial arteries, finger arterial pressure and electrocardiographic R-R' interval were monitored beat-by-beat, before, during and for 3 min following counterflow bolus injections into the abdominal aorta of 40 ml/2.6 s of iopamidol (I), iso-osmolar mannitol (M) and 0.9 N saline (S), in 11 hypertensive and nine normotensive patients. RESULTS: After bolus injection of iopamidol, MBV increased to a peak at 35+/-5 s, both in normotensive (deltaMBV versus baseline +16.7+/-9.9 cm/s; P < 0.01) and in hypertensive subjects (deltaMBV versus baseline: +13.9+/-6.6 cm/s; P < 0.01). At the same time, the PI decreased both in normotensive (deltaPI versus baseline: -4.05+/-2.49; P < 0.01) and in hypertensive subjects (deltaPI versus baseline: -3.02+/-2.25; P < 0.01). After M boluses, the haemodynamic changes were of the same direction and magnitude as I for both groups, while after S the magnitude was approximately 50% lower. No significant differences were observed between normotensive and hypertensive subjects. In other vascular circulations, a 15% increase of the early diastolic backflow in the brachial artery, in phase with the femoral artery haemodynamic changes, was the only evidence of the procedure. Mean arterial pressure decreased and heart rate increased in phase with flow changes of the femoral artery. CONCLUSIONS: (1) The regional flow and systemic pressure changes observed during aortography seem, at least partially, to be due to the hydrodynamic perturbation induced by bolus injection per se. (2) The physical and chemical properties of the contrast media and therefore the probable different shear-stress modifications induced by the fluid injected could explain why the haemodynamic changes were greater after I compared to S and were more similar to M. (3) Hypertensive subjects did not show a different vasoreactive response in comparison to normotensive subjects during aortography.

Haemoconcentration, shear-stress increase and carotid artery diameter regulation after furosemide administration in older hypertensives.

The aim of the present study was to determine whether changes of carotid wall shear stress induced by changes in blood viscosity after diuretic administration cause carotid arterial dilatation in elderly hypertensives, as reported in the cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the systo-diastolic diameter (echotracking technique) and the mean blood flow velocity and volume of the common carotid artery, the blood viscosity (rotational viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists up to 24h before the study, both at baseline and after intravenous furosemide infusion (0.5mg/min), when the haematocrit had increased by at least two percentage points. After furosemide administration the mean arterial blood pressure decreased and blood viscosity and carotid systolic shear stress increased in both groups. However, common carotid artery diameter increased only in the young controls but not in the elderly hypertensives. These data show that an increase in carotid shear stress caused by haemoconcentration induces carotid vasodilatation only in young healthy subjects, and not in elderly hypertensives. This effect may be related to impaired endothelium function and/or arterial wall mechanics.