Improvement Of Arterial Function Research Articles

EFFECT OF ANTI–PCSK9 ANTIBODIES ON ARTERY STRUCTURE AND FUNCTION: THE NIGUARDA HOSPITAL COHORT

Abstract Background PCSK9 inhibitors antibodies (PCSK9–i) are a valid option to reduce LDL cholesterol in patients who failed to reach therapeutic target with maximized lipid–lowering therapies or in patient with statins intolerances. These antibodies reduce the frequency of new cardiovascular events, however if this effect is due only to LDL reduction or also to an improvement in arterial function and structure is yet to be proved. Our study aim was to evaluate aortic stiffness (Pulse Wave Velocity – PWV), carotid’s Intima–Media Thickness (IMT) and endothelial function (brachial Flow Mediated Dilatation – FMD) in patients treated with Alirocumab and Evolocumab. Methods This is a monocentric prospective longitudinal study on patients who received PCSK9–i administrations at the Niguarda Hospital’s cardiovascular rehabilitation and prevention unit. They underwent 3 evaluations of PWV, FMD and IMT (T0 the same day of the first injection, T1 after 6 months and T2 after 12 months of therapy). Results 39 patients concluded the 12 months period. The group average age is 66.8 ± 7.6 years, most of them were male (64.1%). LDL cholesterol average levels were significantly reduced by the therapy (128.3 ± 27.7 vs 44.7 ± 29.3 mg/dL, p<0.001), however, there were no significant changes in PWV (10.2 ± 3.0 vs 10.6 ± 2.5 m/s, p=0.404), FMD (8.6 ± 7.0 vs 8.9 ± 7.4 %, p=0.560) and IMT (768.7 ± 175.4 vs 733.5 ± 147.2 µm, p=0.270) values. Conclusions It was not possible to prove a significant effect of PCSK9–i on vascular properties, however, the stability of these indexes may suggest a deceleration of the atherosclerotic disease which it could have worsen in this population, especially considering the risk factors of our patients.

Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction.

Systemic inhibition of the mammalian target of rapamycin (mTOR) delays aging and many age-related conditions including arterial and metabolic dysfunction. However, the mechanisms and tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation of S6K, a downstream target of mTOR, is increased in arteries with advancing age, and that this occurs preferentially in the endothelium compared with the vascular smooth muscle. Induced endothelial cell-specific deletion of mTOR reduced protein expression by 60-70%. Although this did not significantly alter arterial and metabolic function in young mice, endothelial mTOR reduction reversed arterial stiffening and improved endothelium-dependent dilation (EDD) in old mice, indicating an improvement in age-related arterial dysfunction. Improvement in arterial function in old mice was concomitant with reductions in arterial cellular senescence, inflammation, and oxidative stress. The reduction in endothelial mTOR also improved glucose tolerance in old mice, and this was associated with attenuated hepatic gluconeogenesis and improved lipid tolerance, but was independent of alterations in peripheral insulin sensitivity, pancreatic beta cell function, or fasted plasma lipids in old mice. Lastly, we found that endothelial mTOR reduction suppressed gene expression of senescence and inflammatory markers in endothelial-rich (i.e., lung) and metabolically active organs (i.e., liver and adipose tissue), which may have contributed to the improvement in metabolic function in old mice. This is the first evidence demonstrating that reducing endothelial mTOR in old age improves arterial and metabolic function. These findings have implications for future drug development.

Empagliflozin-Metformin Combination Has Antioxidative and Anti-Inflammatory Properties that Correlate with Vascular Protection in Adults with Type 1 Diabetes

Methods 40 individuals with type 1 diabetes (average age of 44.7 ± 2.5 years) were randomized into four groups: (1) control (placebo), (2) empagliflozin 25 mg daily, (3) metformin 2000 mg daily, and (4) empagliflozin-metformin combination (25 mg and 2000 mg daily, respectively). At inclusion and after 12 weeks of treatment, the blood samples were collected, and the oxidative stress (total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, advanced oxidation protein products (AOPP), advanced glycosylation end products ((AGE) and isoprostane), and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) parameters were determined. Results The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001). Antioxidative action was associated with the improvement in arterial function (obtained in the previous study) in the empagliflozin-metformin combination group. Conclusion Empagliflozin-metformin combination has strong antioxidative and anti-inflammatory capacity, in adults with type 1 diabetes that is greater than that for the individual drugs. Its antioxidative activity at least partially explains the improvement in arterial function. Therefore, it appears that the combination provides the most powerful vascular protection.

EVALUATION OF THE EFFECTS OF MONACOLIN K ON LIPID PROFILE AND ARTERIAL FUNCTION IN DYSLIPIDEMIC PATIENTS

Objective: dyslipidemia is the major Cardio-Vascular (CV) risk factor after hypertension. Some natural derivative molecules are able to improve the lipid profile, including monocolin K. This substance, which inhibits cholesterol synthesis, is produced by the fermentation of the red rice by a mycetes (Monascus Purpureus). Monacolin K is also known as lovastatin, but recent data show that compared to classic lovastatin, monacolin K would have a higher bioavailability, a greater efficacy at the same dosage and a satisfactory tolerability. Its role as an hypolipidemic therapy is accounted in guidelines but, to date, the effect on arterial functional and structural parameters has never been evaluated. Design and method: we evaluated 20 patients (11 females) with mild to moderate dyslipidemia (LDL cholesterol between 100–160 mg/dL) before and after three months from monacolin therapy starting. Obesity, hypertension (defined as BP values > 140/90 mmHg or anti-hypertensive therapy) and alterate glycemic state Inclusione criteria were Patients were non-obese, normotensive and normoglycemic. Serum lipids, Blood Pressure (BP) and Pulse Wave Velocity (PWV – Complior). Results: at baseline mean age was 43.4 ± 10.2, BP 121 ± 14/76 ± 9.3 and Heart Rate (HR) 67.2 ± 7.6. Treatment lead to a significant reduction of total and LDL cholesterol (total: 258.4 ± 25.9 versus 228.5 ± 28.4 mg/dL after 3 months, p < 0.001; LDL: 167.3 ± 31.2 versus 140.8 ± 25.2 mg/dL after 3 months, p < 0.001) and a significant improvement of arterial stiffness (PWV: 8.0 ± 1.4 versus 7.6 ± 1.2 m/s after 3 months, p = 0.02). No significant differences were seen for Systolic BP (121 ± 14 versus 118.3 ± 15.5 mmHg after 3 months, p = ns) and HR (67.2 ± 7.6 vs 69 ± 5.1 bpm after 3 months, p = ns) while a slight improvement for Diastolic BP (76 ± 9.3 vs 72.8 ± 8.3 mmHg after 3 months, p = 0,004) was found. Conclusions: the results of the present study confirm that the treatment with monacolin K reduces significantly the levels of total and LDL cholesterol. They also show that a so brief treatment course of only 3 months induces an improvement in arterial function as showed by the reduction in pulse wave velocity without changes in BP and HR.

Episodic bouts of hyperaemia and shear stress improve arterial blood flow and endothelial function.

Exercise and heat stress lead to systemic improvements in arterial endothelial function, vascular stiffness, and cardiopulmonary capacity. The improvements in endothelial function may be primarily mediated via increases in shear stress. This study examined whether improvements in arterial function may be achieved in the absence of systemic vascular adaptations. Specifically, we hypothesized that repeated bouts of brief occlusion would improve arterial endothelial function via shear stress-dependent mechanisms. Eleven healthy males underwent a shear stress intervention (5s brachial occlusion, 10s rest) for 30min, five times weekly for 6weeks on one arm while the other acted as an untreated control. Ultrasound was used to assess brachial arterial forearm blood flow (FBF) and vascular conductance (FVC), diameter, and shear rate (SR), while endothelial function was assessed by flow-mediated dilatation (FMD). Post-occlusive reactive hyperaemia and pulse wave velocity (PWV) were also measured. There were no changes in any of the measures in the control arm (all d < 0.2, p > 0.05). After 3 weeks of the intervention, FMD was increased from baseline (7.6 ± 0.6 vs. 5.9 ± 0.9%; d = 1.3, p = 0.038) and further increased after 6 weeks to 9.5 ± 2.6% (d = 1.7, p < 0.001). SR was also increased following the 6-week intervention (all d ≥ 0.6, p < 0.001). Resting and peak FBF and FVC were also increased in response to the intervention (all d ≥ 0.6, p < 0.001) and PWV was reduced. These data demonstrate that episodic increases in shear stress elicit marked increases in arterial endothelial function and vascular reactivity.

Near Infrared Spectroscopy (NIRS) can detect improvements in arterial function following 6-months of marathon training

Near Infrared Spectroscopy (NIRS) can detect improvements in arterial function following 6-months of marathon training

Early Improvements in Blood Lipid Profile and Vascular Alterations after Gastric Bypass Surgery Prior to Dramatic Weight Loss

With 6.6% of adults in the U.S. classified as morbidly obese, excess bodyweight is now the sixth most significant risk factor contributing to the overall burden of disease, emerging as one of the most serious public health concerns in the 21st century. Bariatric surgery has been shown to eliminate comorbid conditions associated with obesity. The aim of this study is to evaluate the effect of weight reduction following laparoscopic Roux‐en Y gastric bypass (RYGB) on remodeling and improvements in arterial function, in addition to immediate reversal of metabolic deviations as weight is lost.Patients that meet protocol inclusion criteria are invited to join the study during their 1 week pre‐operative clinical appointment. At this time patients are consented and instructed to lie supine for 10 minutes of quite relaxation. Patients then begin a sequence of non‐invasive examinations starting with a 12‐lead electrocardiogram, followed by an echocardiogram, carotid artery ultrasound, radial applanation tonometry, and endothelial function analysis using EndoPAT technology. Upon completion of the non‐invasive procedures a fasting blood sample is taken for analysis.Preliminary findings show that RYGB results in significant body weight reduction (pre: 131.8 ±5.6 to post: 125 ±5.2 kg) in morbidly obese subjects, along with reductions in BMI (pre: 45.2 ±2.3 to post: 42.9 ± 2.2) and waist circumference (pre: 122.1 ±5.0 to post: 111.9 ± 3.2 cm) at the 1‐week time point. Decrease in body size and weight was aided by a reduction in low‐density lipoprotein (pre: 127 ±6.2 to post: 113 ±4.5 mg/dL), as well as suggested decreases in glucose levels. Such changes can be associated with an improvement of the lipid and glucose metabolism. However, these results appear before subjects have lost a substantial amount of weight (one week post‐operative), suggesting that noteworthy cardiovascular improvements post‐RYGB are achieved prior to the hypothesized weight‐related change. In addition, a number of improvements to the cardiovascular system were also marked at the 1‐week time point. Estimated left ventricular end systolic pressure and direct measure of left ventricular end systolic volume (pre: 66 ±4 to post: 55 ±3 mmHg) declined post‐GBS with an array of additional markers supporting alterations in central systolic blood pressure and myocardial oxygen demand. The data suggests that vascular changes are happening in the early stages of recovery, prior to dramatic weight loss, thus suggesting vascular modifications are a result of an alternate surgical benefit.

Abstract P303: Early Changes in Vascular Structure and Function after Bariatric Surgery in an Appalachian Population

Obesity is associated with an elevated risk of cardiovascular disease, metabolic disease, and cardiac mortality. Reactive oxygen species and inflammation in an obese individuals are among a number of suspected driving forces behind obesity’s detrimental health effects. These factors can elevate cardiovascular risk by causing impairments in cardiovascular structure and function. It is hypothesized that gastric bypass surgery will lead to near immediate reversal of metabolic deviations and rapid weight reduction, in addition to remodeling and improvements in arterial function as weight is lost. Patients that meet protocol inclusion criteria are invited to join the study during their 1 week pre-operative clinical appointment. At this time patients are consented and instructed to lie supine for 10 minutes of quite relaxation. Patients then begin a sequence of non-invasive examinations starting with a 12-lead electrocardiogram, followed by an echocardiogram, carotid artery ultrasound, radial applanation tonometry, and endothelial function analysis using EndoPAT technology. Upon completion of the non-invasive procedures a blood sample is taken for analysis. Preliminary results on 12 study subjects suggests the following. As hypothesized, body weight had decreased (pre: 131.8 ±5.6 to post: 125 ±5.2 kg) along with BMI (pre: 45.2 ±2.3 to post: 42.9 ± 2.2) and waist circumference (pre: 122.1 ±5.0 to post: 111.9 ± 3.2 cm) at the 1-week time point. Decrease in body size and weight was aided by a reduction in low-density lipoprotein (pre: 127 ±6.2 to post: 113 ±4.5 mg/dL). In addition, a number of improvements to the cardiovascular system were also marked at the 1-week time point. Estimated left ventricular end systolic pressure and direct measure of left ventricular end systolic volume (pre: 66 ±4 to post: 55 ±3 mmHg) declined post-GBS. This is in consort with an increase in contraction rate (dP/dt pre: 672 ±54 post: 737 ±46, p&lt;0.01), a reduction in LV ejection time (pre: 291 ±10 to post: 211 ± 30ms), and a decrease in myocardial oxygen demand (PTIs pre: 2346 ±120 post: 2194 ±107 area/min, p&lt;0.05). Similar improvements in augmentation index can be seen in assessments of peripheral vessels. Independent of brachial artery blood pressure, central systolic blood pressure (pre: 112 ± 4 to post: 105 ±2 mmHg, p=0.08), augmentation index (pre: 16 ±3 to post: 8 ±3, p=0.06), an indirect measure of arterial stiffness, and central augmentation pressure (pre: 4.9 ±1.1 to post: 2.5 ±0.9 mmHg, p=0.06) tended to decrease 1-week post GBS. The data suggests that vascular changes are happening in the early stages of recovery, prior to dramatic weight loss, thus suggesting vascular changes are a result of an alternate surgical benefit. In conclusion, the preliminary results of this study suggest noteworthy cardiovascular improvements post-gastric bypass surgery, yet prior to significant weight loss.

The effect of water immersion during exercise on cerebral blood flow.

Regular exercise induces recurrent increases in cerebrovascular perfusion. In peripheral arteries, such episodic increases in perfusion are responsible for improvement in arterial function and health. We examined the hypothesis that exercise during immersion augments cerebral blood flow velocity compared with intensity-matched land-based exercise. Fifteen normotensive participants were recruited (26 ± 4 yr, 24.3 ± 1.9 kg·m). We continuously assessed mean arterial blood pressure, HR, stroke volume, oxygen consumption, and blood flow velocities through the middle and posterior cerebral arteries before, during, and after 20-min bouts of water- and land-based stepping exercise of matched intensity. The order in which the exercise conditions were performed was randomized between subjects. Water-based exercise was performed in 30°C water to the level of the right atrium. The water- and land-based exercise bouts were closely matched for oxygen consumption (13.3 mL·kg·min (95% confidence interval (CI), 12.2-14.6) vs 13.5 mL·kg·min (95% CI, 12.1-14.8), P = 0.89) and HR (95 bpm (95% CI, 90-101) vs 96 bpm (95% CI, 91-102), P = 0.65). Compared with land-based exercise, water-based exercise induced an increase in middle cerebral artery blood flow velocity (74 cm·s (95% CI, 66-81) vs 67 cm·s (95% CI, 60-74) P < 0.001), posterior cerebral artery blood flow velocity (47 cm·s (95% CI, 40-53) vs 43 cm·s (95% CI, 37-49), P < 0.001), mean arterial blood pressure (106 mm Hg (95% CI, 100-111) vs 101 mm Hg (95% CI, 95-106), P < 0.001), and partial pressure of expired CO2 (P ≤ 0.001). Our findings suggest that water-based exercise augments cerebral blood flow, relative to land-based exercise of similar intensity, in healthy humans.

Daily non-soy legume consumption reverses vascular impairment due to peripheral artery disease

ObjectivePeripheral artery disease (PAD) results from a decrease in blood flow to the limbs due to the presence of atherosclerotic plaque. It has been reported that isoflavones isolated from soybeans reduce arterial stiffness, a component of atherosclerotic disease. This study examined the effect of consuming whole legumes (non-soy) on arterial function in humans with PAD. MethodsTwenty-six individuals with PAD consumed ½ cup/day cooked legumes (beans, peas, lentils, chickpeas) daily for 8 weeks. Measurements of circulating factors and vascular function at baseline and study conclusion were compared. ResultsNo changes in were detected relative to baseline values for most parameters. Total and LDL-cholesterol were reduced by 5.0% and 8.7%, respectively. The ankle-brachial index (ABI) showed a 5.5% increase. Changes in ABI and LDL-cholesterol did not correlate. Serum markers of endothelial dysfunction and inflammation were unchanged, but short-chain acylcarnitine concentrations were significantly decreased. ConclusionsA legume-rich diet can elicit major improvements in arterial function and serum cholesterol in the absence of changes in either body mass or blood pressure, although the improvements in vascular function and serum lipids were unrelated. Although the positive results obtained with this dietary intervention were not explained by biomarkers of endothelial function and inflammation, altered acylcarnitine levels indicate an improvement in skeletal muscle metabolism due to enhanced tissue perfusion.

Treatment With Low-dose Atorvastatin, Losartan, and Their Combination Increases Expression of Vasoactive-Related Genes in Rat Aortas

Recently it has been shown that statins and angiotensin receptor blockers (ARBs) at low doses express beneficial pleiotropic vascular effects. We aimed to explore whether these drugs at low doses induce the expression of vasoactive-related genes. Sixty adult Wistar rats were treated with low-dose atorvastatin (2 mg/kg), low-dose losartan (5 mg/kg), their combination or saline daily for 4, 6, or 8 weeks. Expression of the vasoactive-related genes endothelin receptor type A (EDNRA), endothelial nitric oxide synthase 3 (NOS3), inducible nitric oxide synthase 2 (NOS2), and angiotensin II receptor type 1 (AGTRL1a) was measured in isolated thoracic aortas. Expression of EDNRA gradually decreased, the lowest values being obtained after 8 weeks (low-dose atorvastatin, losartan [1.6- and 1-7-fold vs controls, respectively; both P < .05], and the combination [2.3-fold vs control, P < .001]). The highest values of NOS3 were obtained after 6 weeks (low-dose atorvastatin, losartan, and their combination, 3.1-fold, P < .01; 3.4-fold, P < .001; and 3.6-fold, P < .001 vs controls, respectively) and then declined after 8 weeks. The combination was more effective in inducing total NOS3 expression when compared to the separate drugs (1.4-fold; P < .05). Importantly, expression of NOS3 was associated with increased plasma NO levels and positively correlated with thoracic aorta relaxation. No changes in expression of NOS2 and AGTRL1a were observed. We showed that low-dose atorvastatin or losartan and especially their combination increases the expression of NOS3 and decreases the expression of EDNRA. These findings are valuable in explaining the effectiveness of the "low-dose pharmacological approach" for improvement in arterial function.

The effects of low-dose fluvastatin and valsartan combination on arterial function: A randomized clinical trial

BackgroundAgeing progressively diminishes arterial functions, even in the absence of traditional risk factors. Our aim was to explore whether age-related arterial changes in middle-aged males could be reversed using short-term, low-dose fluvastatin/valsartan combination intervention. MethodsForty apparently healthy, middle-aged males (43.3±5.8years) were recruited in a double-blind, randomised intervention. Individuals received either 10mg fluvastatin/20mg valsartan daily or placebo over 30days. The brachial artery flow mediated dilation (FMD), pulse wave velocity (PWV) and common carotid artery β-stiffness were assessed at baseline and after 30days, and again 5–10months after therapy discontinuation. ResultsArterial function variables significantly improved after 30days of intervention; FMD improved by 167.7% (P<0.001), PWV by 10.9% (P<0.05) and β-stiffness by 18.8% (P<0.01), whereas no changes were obtained in the placebo group. The favourable outcomes in the intervention group were accompanied by a significant decrease of high sensitivity-C reactive protein levels (1.8-fold; P<0.05). In contrast, lipids and blood pressure remained unchanged. Surprisingly, the beneficial arterial effects were still present to a substantial degree 7months after completing intervention (remaining % of initial improvement: FMD 82.1%, PWV 69.5% and β-stiffness 68.5%), but declined substantially after 10months. ConclusionOur results indicate that age-related arterial changes, at least in middle-aged males, can be reversed. Short-term treatment with a low-dose fluvastatin/valsartan combination resulted in a large and long lasting improvement of arterial function.

Arterial Stiffness in the Young: Assessment, Determinants, and Implications

Arterial stiffness describes the rigidity of the arterial wall. Its significance owes to its relationship with the pulsatile afterload presented to the left ventricle and its implications on ventricular-arterial coupling. In adults, the contention that arterial stiffness as a marker and risk factor for cardiovascular morbidity and mortality is gaining support. Noninvasive methods have increasingly been adopted in both the research and clinical arena to determine local, segmental, and systemic arterial stiffness in the young. With adoption of these noninvasive techniques for use in children and adolescents, the phenomenon and significance of arterial stiffening in the young is beginning to be unveiled. The list of childhood factors and conditions found to be associated with arterial stiffening has expanded rapidly over the last decade; these include traditional cardiovascular risk factors, prenatal growth restriction, vasculitides, vasculopathies associated with various syndromes, congenital heart disease, and several systemic diseases. The findings of arterial stiffening have functional implications on energetic efficiency, structure, and function of the left ventricle. Early identification of arterial dysfunction in childhood may provide a window for early intervention, although longitudinal studies are required to determine whether improvement of arterial function in normal and at-risk paediatric populations will be translated into clinical benefits.

Dose-dependent increases in heart rate variability and arterial compliance in overweight and obese adults with DHA-rich fish oil supplementation

Heart rate (HR) variability and large arterial compliance can be improved using fish oils. DHA, a component of fish oil, has cardiovascular health benefits, but its effect on HR variability (HRV) and arterial compliance is yet to be quantified. Sixty-seven overweight or obese adults (thirty-six males and thirty-one females; 53 (sem 2) year; BMI 31.7 (sem 1.1) kg/m(2)) were randomly allocated to consume either 6 g/d sunola oil (control; n 17), fish oil (260 mg DHA+60 mg EPA per g) at doses of 2 g/d (n 16), 4 g/d (n 17) or 6 g/d (n 17). Blood pressure, HR and compliance of large and small arteries were measured while supine at baseline and after 12 weeks in all participants, and HRV was assessed in a subgroup of forty-six participants. There was no effect of fish oil on blood pressure, small artery compliance or HR. However, the low frequency:high frequency ratio of HRV decreased with increasing doses of fish oil (r - 0.34, P = 0.02), while large artery compliance increased (r 0.34, P = 0.006). Moreover, the changes in these biomarkers were significantly correlated (r - 0.31, P = 0.04) and may reflect fish oil-induced improvements in arterial function and cardiac autonomic regulation.

Increased consumption of legumes improves arterial stiffness in peripheral vascular disease independent of blood pressure, weight and serum cholesterol

BackgroundEating fibre‐rich, low glycemic legumes may benefit cardiovascular health by reducing plasma lipid levels. We therefore undertook a clinical study to address the hypothesis that increased legume consumption would improve arterial stiffness.MethodsIndividuals with peripheral arterial disease were given ½ cup mixed legumes daily for 8 wks.ResultsNo changes in glycated hemoglobin, blood pressure, body weight, triglycerides or HDL cholesterol were detected relative to baseline values, but there were significant decreases in total and LDL cholesterol. There was an improvement in ankle‐brachial index (ABI) and a corresponding decrease in arterial stiffness (by pulse wave analysis), but serum markers of endothelial dysfunction or inflammation remained constant. Interestingly, the improvements in ABI and cholesterol were not correlated.ConclusionsThese data indicate that a legume‐rich diet can elicit major improvements in arterial function in the absence of changes in either body mass or blood pressure. Furthermore, the lack of correlation with serum cholesterol levels suggests improved vascular function was not a consequence of the high fibre and low glycemic index properties of the legumes. Finally, the absence of changes in circulating markers of endothelial dysfunction suggests the positive effects on arterial stiffness are mediated by another mechanism.Funding from Pulse Canada.

Improvements in Arterial Function Following Weight Loss in Morbidly Obese Type 2 Diabetes is Predicted by Changes in Visceral Obesity and Reduced Activation of Circulating Monocytes

Improvements in Arterial Function Following Weight Loss in Morbidly Obese Type 2 Diabetes is Predicted by Changes in Visceral Obesity and Reduced Activation of Circulating Monocytes

Exercise training increases arterial compliance in patients with congestive heart failure

Systemic arterial compliance (SAC) makes an important contribution to cardiac afterload, and thus is a significant determinant of left ventricular work. Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure (CHF), and that SAC is increased after a 4-week exercise training programme in healthy, sedentary individuals. The present study aimed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties, left ventricular performance and quality of life in CHF patients. A total of 21 patients with NYHA class II or III CHF (mean+/-S.D. age 55+/-13 years) were randomly allocated to either an 8-week exercise training group or a "usual lifestyle" control group. SAC, as determined non-invasively using applanation tonometry and Doppler aortic velocimetry, increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units (mean+/-S.E.M.; P=0.01) in the exercise group, while no change occurred in the control group. Left ventricular structure and function was assessed by echocardiography, and these parameters were unchanged over the 8-week study period. Exercise training significantly increased exercise capacity, measured by a 6-min walking test (474+/-27 to 547+/-34 m; P=0.008). Quality of life, as assessed using the Minnesota Living with Heart Failure Evaluation, demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units (P=0.01) following the exercise training programme. These data show that exercise training improves SAC in patients with CHF. The accompanying improvement in exercise capacity may be due, in part, to an improvement in arterial function.

Do we need clinical trials to test the ability of transdermal HRT to prevent coronary heart disease?

Postmenopausal hormone replacement therapy (HRT) with oral oestrogen was predicted to reduce coronary heart disease (CHD) risk by 50%. Randomized controlled trials show no such benefit, however, pointing instead to an initial increase in CHD events. Although the cardiovascular effects of transdermal HRT are largely unknown, improvements in arterial function are maintained when oestrogen is administered transdermally. Transdermal HRT also avoids the increased plasma levels of C-reactive protein (CRP) that are seen with oral HRT. However, the clinical significance of this general reduction in hepatic over-synthesis of plasma proteins is difficult to assess. Nevertheless, the available evidence on transdermal HRT appears to justify a formal clinical trial.