Surrogate Markers Of Cardiovascular Risk Research Articles

S14 CPAP improves endothelial function in minimally symptomatic OSA patients: results from the MOSAIC trial

BackgroundCPAP treatment for symptomatic OSA improves surrogate markers of cardiovascular risk, such as endothelial function and arterial stiffness, and may reduce actual cardiovascular events. Minimally symptomatic OSA is far more...

Primary biliary cirrhosis is associated with oxidative stress and endothelial dysfunction but not increased cardiovascular risk

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti-oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk. Fifty-one PBC patients and 34 control subjects were studied. Lipid soluble vitamins A, and E in addition to ascorbate and carotenoids were measured to assess anti-oxidant status. C-reactive protein, hydroperoxides and adhesion molecules sICAM-l/sVCAM-l were assessed as serological measures of endothelial function. Finally, measures of vascular compliance were assessed by applanation tonometer. CRP, sICAM and sVCAM were all significantly higher in PBC patients (469.14 vs 207.13, P < 0.001; 768.12 vs 308.03,P < 0.001; 708.40 vs 461.31, P < 0.001) whilst anti-oxidant vitamin levels were lower in PBC patients, with ascorbate, vitamin E and vitamin A all significantly lower in PBC patients (39.91 vs 72.68, P < 0.001; 2.63 vs 3.14, P = 0.02; 1.08 vs 1.81, P < 0.001). Despite these findings PBC patients have a lower pulse wave velocity than control subjects (8.22 m/s vs 8.78 m/s, P = 0.022). PBC patients appear to have reduced vascular risk as assessed by pulse wave velocity but concurrently have evidence of endothelial dysfunction, inflammation and anti-oxidant deficiency.

Incretin therapy for type 2 diabetes mellitus

In addition to progressive pancreatic β-cell failure resulting in impaired insulin secretion, and increased insulin resistance in muscle and liver, incretin hormone-related abnormalities have been identified as key underlying defects in patients with type 2 diabetes mellitus. Treatment goals for patients with type 2 diabetes should be aligned with the basic defects of the disease. Many of the available antidiabetes agents correct hyperglycemia but do not impact other cardiovascular risk factors, and may actually aggravate some. This paper reviews the role of defects in the incretin system in the pathophysiology of type 2 diabetes, and discusses recent advances in the use of incretinbased agents that target the fundamental disease mechanisms of type 2 diabetes. The incretinbased agents reduce hyperglycemia and provide beneficial effects on surrogate markers of cardiovascular risk, including weight gain, elevated blood pressure, and dyslipidemia.

Central blood pressure estimation for the masses moves a step closer

The sphygmomanometer is one of the few medical devices that can be truly said to have stood the test of time. This is in part testament to its simplicity and ease of use, but also that 100 years of careful epidemiological observation and large-scale intervention trials have placed the predictive value of brachial blood pressure beyond question. Despite this, over the last 30 years a few visionaries, or ‘heretics’, depending on one’s viewpoint, have fought for greater recognition of the potential clinical importance of aortic (central) pressure. Their rationale stemmed from the observation, first made at the time of invasive cardiac catheterization, that aortic and brachial systolic pressures vary considerably, and, more recently, that surrogate markers of cardiovascular risk are better related to central systolic pressure than the corresponding brachial artery values. Since then, evidence has accrued that central pressure may actually be an independent predictor of future cardiovascular risk, supporting the visionaries. However, central pressure measurement and its use in risk stratification are yet to enter the clinical arena for two main reasons:

Polyphenols and health: Update and perspectives

Current issues in research on health effects by polyphenols are addressed. As to the cardiovascular system, flow-mediated dilation (FMD), a functional biomarker, can be used as surrogate marker for cardiovascular risk. Acute short-term effects peaking at 2 h after ingestion of polyphenol-rich food items are distinguished from longer-term effects over days and weeks. The role of polyphenol metabolites as bioactives is presented, underlining that specific target enzymes such as NADPH oxidases or lipoxygenases provide a basis for molecular action of polyphenols, rather than unspecific direct antioxidant effects. Cautionary words are given for the use of non-compositional assays of ‘total antioxidant capacity’ (TAC) in blood plasma. Enhanced interest emerges for polyphenols in the gastrointestinal tract. Recommendations for health professionals and the public are summarized, as well as prospects and challenges for future research.

Drospirenone and cardiovascular risk in lean and obese polycystic ovary syndrome patients: a pilot study

We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS). A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B. The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.

Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non‐alcoholic fatty liver disease

Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of atherosclerosis and alanine aminotransferase (ALT) is associated with insulin resistance independently of metabolic factors. The aim of the present study was to investigate whether NAFLD patients with ALT elevation had a higher risk of carotid atherosclerosis. A total of 190 individuals were enrolled from the health management center. Among them, 20 subjects were excluded due to the presence of hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and cardiovascular disease. NAFLD was diagnosed by ultrasound examination. Carotid ultrasonography was used to measure maximal intima-media thickness (IMT) of the common carotid artery (CCA) and IMT (mean) > 1.0 mm was defined as the presence of carotid atherosclerosis. NAFLD patients with ALT elevation had increased risk of carotid atherosclerosis than those with normal ALT by Fisher's exact test (P < 0.05). Multivariate analyses showed that serum ALT levels were positively associated with carotid atherosclerosis after adjustment for age, sex, number of metabolic syndrome components or status of metabolic syndrome (OR, 1.44; 95% CI 1.09-1.89; OR, 1.45; 95% CI 1.11-1.91). In addition, the higher the serum ALT levels with every 10 IU/L increment, the greater the risk of carotid atherosclerosis. Serum ALT levels are positively associated with the risk of carotid atherosclerosis in patients with NAFLD, suggesting that serum ALT levels could serve as a surrogate marker of cardiovascular risk in this special clinical setting.

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study

Background and Aim Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. Methods and Results The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54 mg of genistein aglycone ( n = 71) or placebo ( n = 67), daily. Both arms received calcium and vitamin D 3 in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. Conclusions After 3-years of treatment, genistein aglycone plus calcium, vitamin D 3 and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Blood Pressure–Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease

Endothelin 1 is implicated in the development and progression of chronic kidney disease and associated cardiovascular disease. We, therefore, studied the effects of selective endothelin-A receptor antagonism with BQ-123 on key independent surrogate markers of cardiovascular risk (blood pressure, proteinuria and renal hemodynamics, arterial stiffness, and endothelial function) in patients with nondiabetic chronic kidney disease. In a double-blind, randomized crossover study, 22 subjects with proteinuric chronic kidney disease received, on 2 separate occasions, placebo or BQ-123. Ten of these subjects also received nifedipine (10 mg) as an active control for the antihypertensive effect of BQ-123. Blood pressure, pulse wave velocity, flow-mediated dilation, renal blood flow, and glomerular filtration rate were monitored after drug dosing. BQ-123 reduced blood pressure (mean arterial pressure: -7+/-1%; P<0.001 versus placebo) and increased renal blood flow (17+/-4%; P<0.01 versus placebo). Glomerular filtration rate remained unchanged. Proteinuria (-26+/-4%; P<0.01 versus placebo) and pulse wave velocity (-5+/-1%; P<0.001 versus placebo) fell after BQ-123, but flow-mediated dilation did not change. Nifedipine matched the blood pressure and renal blood flow changes seen with BQ-123. Nevertheless, BQ-123 reduced proteinuria (-38+/-3% versus 26+/-11%; P<0.001) and pulse wave velocity (-9+/-1% versus -3+/-1%; P<0.001) to a greater extent than nifedipine. Selective endothelin-A receptor antagonism reduced blood pressure, proteinuria, and arterial stiffness on top of standard treatment in renal patients. Furthermore, these studies suggest that the reduction in proteinuria and arterial stiffness is partly independent of blood pressure. If maintained longer term, selective endothelin-A receptor antagonism may confer cardiovascular and renal benefits in patients with chronic kidney disease.

The Art of Primary Prevention and Risk Assessment

See related article, pages 730–736. The paradigm that homocysteine is associated with atherosclerotic disease has been discussed since the 1960s. Since then, large observational studies and meta-analyses showed a strong relationship between homocysteine and cardiovascular risk. However, several recent trials using homocysteine-lowering therapies for secondary prevention failed to show beneficial effects in patients with prior stroke or known coronary artery disease.1–3 These trials showed no advantage of either folic acid and/or vitamin B complex therapy on “hard” end points such as mortality or cardiovascular events. Thus, the “homocysteine hypothesis” for atherothrombotic disease became controversial. Kaul et al4 stated in a recent review that it remains unclear whether a causal relationship exists between homocysteine and cardiovascular risk, or if homocysteine is related to other confounding risk factors or is a marker of existing disease burden. This discussion is now continued and refuelled with a new study published in this issue of Stroke . Hodis and coworkers present a work that assesses homocysteine-lowering therapy as primary prevention in patients without preexisting cardiovascular disease. The goal was to show a reducing effect of a high-dose combination of B-vitamins on progression of carotid intima media thickness …

Paradoxical role for adiponectin in chronic renal diseases? An example of reverse epidemiology

Adiponectin (ADPN) is an adipocyte-derived protein with potential antiatherogenic properties. In the general population, ADPN serum levels are associated with age and body mass index (BMI), type 2 diabetes and presumably cardiovascular disease. The suspected vascular-protective effects are mediated by several mechanisms such as insulin sensitizing, maintaining endovascular homeostasis and anti-inflammatory properties. Patients with chronic kidney disease (CKD) are subjected to an increased cardiovascular risk. The underlying mechanisms are not yet completely understood although in the last few years numerous studies have linked secondary hyperparathyroidism and inflammation to that risk. It is currently not clear whether, in CKD, ADPN plays the same role as it is thought to do in the general population or if the uremic environment overwhelms the vascular-protective impact of ADPN. Therefore, characterizing ADPN levels and kinetics in CKD and comparing its concentrations with surrogate markers of cardiovascular risk in CKD might contribute to a better understanding of adipocytokine signaling in renal disease. The review summarizes the available literature on ADPN measurement, regulation and therapeutic potential in general population and CKD. In our investigations, ADPN was more than twofold increased in hemodialysis patients compared with the general population. ADPN levels were not associated with age, but with lifetime spent on dialysis (vintage) and BMI. The dialysis procedure had no effect on ADPN. To assess the clinical value of ADPN levels as a potential surrogate of cardiovascular risk in or therapeutic target in CKD, end point-driven studies with special regard to the risk behavior in CKD have to be performed.

Effects of phytoestrogens derived from red clover on atherogenic adhesion molecules in human endothelial cells

In the search for safer approaches to address menopausal symptoms, the administration of plant-derived estrogens has gained popularity. Recent evidence suggests that these compounds may act neutrally or even beneficially on surrogate cardiovascular risk markers in postmenopausal women. However, little is known of the effects of phytoestrogens on vascular cells. Endothelial expression of leukocyte adhesion molecules plays a critical role in the development of atherosclerosis and in plaque destabilization, and estrogen reduces the expression of these proatherogenic molecules. We studied the regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells by phytoestrogens contained in red clover extracts. Moreover, we characterized the mechanistic basis for these actions. Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide. The addition of red clover extracts to reproductive life or menopausal concentrations of 17beta-estradiol results in an additive decrease in expression of endothelial adhesion molecules. The reduction of ICAM-1 and VCAM-1 expression in the presence of red clover extracts is paralleled by a cytoplasmic stabilization of the proinflammatory transcription factor nuclear factor-kappaB. Red clover extracts act as anti-inflammatory and antiatherogenic agents on human endothelial cells by reducing the expression of the leukocyte adhesion molecules ICAM-1 and VCAM-1. On the basis of these results, red clover extracts may induce beneficial actions on human vessels.

Acute effects of haemodialysis on biochemical modulators of endothelial function

To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function. Academic medical centre. Forty patients (age 63.5 +/- 2.2 years, mean +/- SEM) undergoing HD. Folic acid (F), homocysteine (tHcy), asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) were measured pre-HD, 1 h after commencing HD and within the last hour of HD (end-HD). Endothelium-dependent and -independent vasodilatation were measured by applanation tonometry (changes in augmentation index, AIx, postinhaled salbutamol and postsublingual nitroglycerin) in conjunction with biochemical measurements. Marked reductions in serum F (616 +/- 73 vs. 273 +/- 30 nmol L(-1), P < 0.001), tHcy (16.3 +/- 0.7 vs. 11.2 +/- 0.5 micromol L(-1), P < 0.001) and ADMA (0.64 +/- 0.02 vs. 0.47 +/- 0.02 micromol L(-1), P < 0.001) occurred end-HD, whereas CRP and MDA levels did not significantly change. There was no significant change in endothelium-dependent vasodilatation, whereas endothelium-independent vasodilatation improved end-HD (-23.1 +/- 1.9 vs. -17.3 +/- 1.3%, P = 0.018). Regression analysis showed that both higher ADMA (P = 0.029) and lower F levels (P = 0.040) end-HD were determinants of reduced endothelium-dependent vasodilatation end-HD (R(2) = 0.23). HD is associated with significant reductions in F, tHcy and ADMA serum concentrations. The lack of significant effects of HD on endothelium-dependent vasodilatation could be secondary to the concomitant loss of factors either enhancing (F) or impairing (ADMA) endothelial function.

Predictive Factors of Hyperhomocysteinemia in HIV-Positive Patients

Predictive Factors of Hyperhomocysteinemia in HIV-Positive Patients

Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk

Circulating progenitor cells are believed to participate in cardiovascular (CV) homeostasis and their exhaustion has been linked to CV damage. As general agreement on their characterization is lacking, this work was carried out to assess the relationships between different antigenic profiles of progenitor cells and CV risk, with special regard to metabolic syndrome (MetSyn). CD34, CD133, and KDR were used to quantify circulating progenitors in 214 subjects at different levels of CV risk. In a cross-analysis of six different cell subtypes (CD34(+), CD133(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+)), CD34(+) progenitors showed the best correlation with CV parameters and risk estimates. Components of the MetSyn were all characterized by reduction of CD34(+) cells and acted synergistically in decreasing CD34(+) cell count. Moreover, CD34(+) cell count demonstrated a high performance in detecting high CV risk. These data demonstrate that CD34 identifies progenitor cells linked to CV risk, showing a close negative correlation between CD34(+) cells and CV risk, as well as a synergic detrimental effect of clustered metabolic components. Progenitor cell count may be used as a surrogate marker of CV risk, whereas extensive antigenic characterization may not be useful for this purpose.

C-reactive protein and dietary nutrients in urban Asian Indian adolescents and young adults

Objective The relationship between C-reactive protein (CRP), a surrogate marker of cardiovascular risk, and dietary nutrients is not known. We investigated the relationship between serum CRP levels and dietary nutrients in young Asian Indians residing in a major metropolitan city in north India. Methods Dietary nutrient intake values (24-h dietary recall and monthly consumption data) and serum CRP levels were studied in 359 healthy adolescents and young adults (312 male and 47 female) (mean age, 18.0 ± 2.3 y; range, 14–25 y), after carefully excluding those with history of infections and smoking. Bivariate and multivariate logistic regression analysis was performed with CRP [raised (>3.0 mg/L)/normal] as the outcome variable and various dietary nutrients and anthropometric variables as covariates. Results Mean CRP level was 1.3 ± 2.3 mg/L (range, 0.02–17.5 mg/L). Raised CRP levels (>3 mg/L) were noted in 9% study subjects (8.6% males and 12.8% females). After adjustment for other covariates, saturated fat emerged as the single most important nutrient contributing to increase in serum CRP levels. The odds of having a raised CRP level in subjects consuming more than 10% energy as saturated dietary fat were twice as compared to subjects having a normal saturated fat intake [Adjusted odds ratio (OR) (95% CI) = 2.0 (0.94–4.1)]. For every one percent decrease in energy intake by saturated fat, CRP level was calculated to decrease by 0.14 mg/L. For decreasing CRP levels to <1.0 mg/L (low risk for cardiovascular disease), Asian Indian adolescents and young adults should ensure saturated fat intake <7% of caloric intake. Conclusion We suggest that daily saturated fat intake should be limited to <7% of caloric intake in urban adolescents and young adult Asian Indians to decrease their future cardiovascular risk.

Implications of Rosiglitazone and Pioglitazone on Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus

Clinical data suggest that thiazolidinediones--specifically, rosiglitazone and pioglitazone--may improve cardiovascular risk factors through multiple mechanisms. Low insulin sensitivity has been described as an independent risk factor for coronary artery disease and cerebrovascular disease. Patients with insulin resistance often have several known risk factors, such as obesity, dyslipidemia, and hypertension. Other emerging risk factors may be prevalent in patients with insulin resistance, such as hyperinsulinemia, elevated C-reactive protein, elevated plasminogen activator inhibitor levels, and small, dense, low-density lipoproteins. The only available drug class that primarily targets insulin resistance is the thiazolidinediones. These drugs have shown efficacy in affecting surrogate markers of cardiovascular risk in patients with diabetes mellitus. Alterations in these risk factors are likely due to their effects on improving insulin sensitivity and/or glycemic control. Trials to assess whether thiazolidinediones actually reduce cardiovascular outcomes are continuing.

Issue Highlights

HomeCirculationVol. 113, No. 3Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published24 Jan 2006https://doi.org/10.1161/circ.113.3.329Circulation. 2006;113:329MORTALITY AND CARDIOVASCULAR RISK ACROSS THE ANKLE-ARM INDEX SPECTRUM: RESULTS FROM THE CARDIOVASCULAR HEALTH STUDY, by O’Hare et al.The ankle arm index (AAI; ratio of ankle and arm systolic blood pressures) has been used as an indicator of subclinical and clinical peripheral vascular disease, and values below 0.9 and above 1.4 have been reported to indicate an adverse vascular prognosis. In this issue of Circulation, O’Hare and colleagues evaluated the mortality and cardiovascular risks associated with a broad range of AAI (categories defined in 0.1 unit increments from 0.6 to 1.4) in a large elderly community-based sample. Compared to the referent group with an AAI between 1.10 and 1.20, values below 1.0 and above 1.4 were associated with higher all-cause and cardiovascular mortality. Specifically, an AAI in the range 0.9 to 1.0 (often regarded as normal) was associated with a 40% higher mortality risk compared to the referent group, whereas a value above 1.40 was associated with a 57% greater mortality hazard. The authors noted effect modification by age, with stronger associations of high and low AAI with mortality risk in people below age 75 years. Overall, these observational data emphasize the nonlinear relations of AAI and mortality risk and raise the possibility that the mortality risk associated with a low AAI may extend to values above the traditional cut point of 0.9 (ie, to the range 0.9 to 1.0). See p 388.IMPACT OF PROSTHESIS-PATIENT MISMATCH ON LONG-TERM SURVIVAL IN PATIENTS WITH SMALL ST JUDE MEDICAL MECHANICAL PROSTHESES IN THE AORTIC POSITION, by Mohty-Echahidi et al.The issue of prosthesis-patient mismatch continues to be an area of active clinical investigation. The article by Mohty-Echahidi et al focuses on long-term survival in a defined population of patients receiving an aortic valve with a small (19 or 21 mm) St Jude prosthesis. Three-hundred eighty-eight patients were studied and the degree of mismatch was measured by postoperative transesophageal echocardiography in each patient. The effective orifice area index is defined as the echo-derived prosthesis effective orifice area divided by the patient’s body surface area. The patients with severely mismatched effective orifice area index <0.6 cm2/m2 comprised 17% of the study patients. These patients were observed to have a significantly worse survival at 5 years (72%) and 8 years (41%) than those patients with moderate mismatch (0.6 cm2/m2 to 0.85 cm2/m2) or no significant mismatch (>0.85 cm2/m2). Severe mismatch was an independent predictor of mortality (hazard ratio=2.18, P=0.007) and congestive heart failure (hazard ratio=3.1, P= 0.009). The ability of a surgeon to predict potential mismatch should be part of current surgical practice. The effective orifice areas for specific valves are available in tables provided by the manufacturers. The surgeon can calculate the effective orifice area index and choose a hemodynamically superior prosthesis or perform an annular enlargement to avoid mismatch, thus improving outcomes in cardiac surgery. See p 420.EFFECT OF INTENSIVE VERSUS STANDARD LIPID-LOWERING TREATMENT WITH ATORVASTATIN ON THE PROGRESSION OF CALCIFIED CORONARY ATHEROSCLEROSIS OVER 12 MONTHS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND TRIAL, by Schmermund et al.Emerging clinical trials suggest that low-density lipoprotein (LDL) cholesterol lowering beyond previously defined targets improves clinical outcomes in patients with coronary artery disease and those with multiple cardiovascular risk factors. Quantification of coronary artery calcification by electron-beam computed tomography has been shown to provide prognostic information in patients with known or suspected coronary artery disease. In this issue of Circulation, Schmermund et al evaluate whether intensive LDL lowering using high-dose atorvastatin reduces the presence of coronary artery calcification as assessed by electron-beam computed tomography compared to treatment with low dose atorvastatin. In this randomized controlled trial of 471 patients, the mean LDL after 12 months of treatment was 87±33 mg/dL in the high-dose group and was 109±28 mg/dL in the low-dose group. However, the progression in calcium score did not differ between groups. This unexpected funding may have implications for the clinical utility of coronary calcium score as a surrogate marker for cardiovascular risk. See p 427.Visit http://www.circ.ahajournals.org:Images in Cardiovascular MedicineNot So Mural Thrombus. See p e38.Cardiomyopathy Resulting From Primary Hyperoxaluria Type II. See p e39.Role of Inflammation in Atherosclerosis: Immunohistochemical and Electron Microscopic Images of a Coronary Endarterectomy Specimen. See p e41. Download figureDownload PowerPointCorrespondenceSee p e44. Previous Back to top Next FiguresReferencesRelatedDetails January 24, 2006Vol 113, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.113.3.329 Originally publishedJanuary 24, 2006 PDF download Advertisement

Obesity, Weight Loss, and Vascular Function

Obesity promotes the development of several major cardiovascular risk factors. Moreover, excess adiposity may play a direct role in initiating atherosclerosis as fat cells are capable of affecting the systemic vasculature through a variety of mechanisms. Recent studies demonstrate that obesity per se may impair vascular endothelial function. This is important as endothelial dysfunction is a key factor in the pathogenesis of atherosclerosis and in triggering acute ischemic events. At present, few studies have determined the beneficial impact of weight loss on cardiovascular outcomes and mortality. However, several experiments have demonstrated that weight loss can lead to improvements in endothelial function, a validated surrogate marker of cardiovascular risk. The mechanisms whereby weight loss restores vascular health are likely multifactorial. However, the relative importance of reduced adiposity versus the specific dietary regimens prescribed, the role of concomitant exercise, and the direct effect of medications remain unclear. Several other unresolved issues such as the longevity of improvement, the amount of weight loss required, and whether the improvement in endothelial function actually translates into a reduction in cardiovascular events also remain to be determined. Nevertheless, lifestyle changes that lead to weight reduction are able to improve vascular function in overweight adults.

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin] in adults with severe GH deficiency. In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 0.48 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. The LGH decreased fasting glucose levels (P < 0.01) and enhanced insulin sensitivity (P < 0.02), but body composition, nonesterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P < 0.05), CRP (P < 0.05) and IL-6 (P < 0.05) levels, and increased NEFA levels (P < 0.05). No changes were observed with the untreated controls. Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.