High Risk Of Cardiovascular Complications Research Articles

HPLC determination of plasma dimethylarginines: Method validation and preliminary clinical application

Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. The intra- and inter-assay CVs (<5.2%), the absolute and relative recoveries (96-106%) were highly satisfactory. ADMA levels were significantly elevated in all groups of patients compared with controls (p<0.001) with the exception of samples from patients with type II diabetes. SDMA levels were significantly elevated both in the patients with chronic kidney disease and in the patients with type II diabetes complicated by renal insufficiency, the values being closely correlated with both eGFR (R=0.740) and plasmatic creatinine (R=0.700). The findings made in the present study shows that ADMA levels are significantly increased in patients with diseases associated with endothelial dysfunction This molecule might, therefore, be used as a biochemical marker for the evaluation of endothelial function. Furthermore, the preliminary results reported suggest that SDMA might be a reliable marker of renal function, especially in peadiatric populations, for which the use of eGFR is not recommended.

Raising HDL cholesterol levels: a flight of Icarus?

Results of the ARBITER 6–HALTS trial indicate a superiority of the lipid-modifying agent nicotinic acid over ezetimibe for the treatment of atherosclerotic lesions. These findings could have substantial implications for patients worldwide who remain at moderate to high risk of cardiovascular complications because of low levels of HDL cholesterol. But is the evidence substantiated?

Cardiac Surgery, Carotid Stenosis, and Stroke Prevention

Stroke following cardiac surgery is a major source of morbidity and mortality. In patients undergoing cardiac surgery, the presence of severe carotid stenosis is associated with a higher incidence of postoperative stroke. Carotid revascularization procedures, such as carotid endarterectomy and stenting, are frequently performed under such circumstances in an effort to reduce the incidence of stroke. The available literature suggests that most postoperative strokes are not directly related to carotid stenosis. Synchronous carotid revascularization and cardiac surgery renders a higher risk of cardiovascular complications. In this article, we summarize the incidences of postoperative stroke and carotid stenosis in this population, discuss the pathogenesis of stroke in these patients, and propose strategies for managing patients undergoing cardiac surgery with severe carotid stenosis.

El grosor íntimo-medial carotídeo y su utilidad actual

Cardiovascular risk stratification is currently part of routine clinical practice to establish cardiovascular prevention strategies. A complementary approach to the assessment scales of cardiovascular risk stratification is the non-invasive evaluation of the atherosclerotic lesion to identify patients at high risk for cardiovascular complications. Carotid intima-media thickness is a non-invasive method based on ultrasound suitable for the detection of subclinical atherosclerosis. It allows us to stratify cardiovascular risk beyond conventional cardiovascular risk factors and would complement the cardiovascular risk functions. The inclusion of the carotid intima-media thickness in cardiovascular risk stratification may help identify asymptomatic individuals with a high cardiovascular risk not detected by current scales of cardiovascular risk stratification.

Role of carotid ultrasonography in the evaluation of cardiovascular risk in patients with rheumatoid arthritis

We read with great interest the article by Sodergren and colleagues in a recent issue of Arthritis Research & Therapy ('Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness') [1]. In the study reported in the article, the authors showed no differences of carotid artery intima-media thickness (IMT) in patients with very early rheumatoid arthritis (RA) compared with controls at baseline [1]. However, in the subgroup of individuals who were re-evaluated 18 months after the first ultrasound measurement, the carotid IMT had increased significantly among the patients with RA. However, this was not the case for the controls [1]. With respect to these interesting observations, we would like to further emphasize the importance of carotid ultrasonography in the evaluation of the cardiovascular risk of patients with RA and the importance of the duration of the disease as a predictor of severity, so it can influence the development of cardiovascular events in these patients. We previously reported that, in long-standing RA patients with no classic cardiovascular risk factors at the time of the carotid assessment, the duration of the disease was the best predictor of carotid plaques [2]. On the other hand, RA is a chronic inflammatory disease, and even in the apparently quiescent phases of the disease, the cumulative effect of the chronic inflammatory burden may account for the progression of the atherosclerosis disease. In this regard, we observed that the mean values of C-reactive protein (CRP) over an extended follow-up rather than a single determination of CRP at the time of the carotid ultrasonography evaluation were associated with the carotid IMT [3]. Moreover, we found that carotid artery IMT had a high predictive power for the development of cardiovascular events over a 5-year follow-up period in 47 patients with RA without clinically evident cardiovascular disease at the time of the carotid ultrasonography evaluation [4]. In our study, carotid IMT categorized in quartiles was strongly associated with the development of cardiovascular events [4]. When logistic regression models were performed, carotid IMT at the time of the ultrasonographic study yielded a high predictive power for the development of cardiovascular events over the 5-year follow-up period. On the other hand, the duration of the disease is also considered an important risk factor of future cardiovascular events [5]. Taking all of these considerations together, we propose that ultrasonographic assessment of the carotid artery be performed on all patients with RA in order to establish a subgroup of patients with a high risk of cardiovascular complications. This procedure should be carried out at the time of the disease diagnosis and periodically there-after, in particular in those patients with severe disease and persistent elevation of markers of inflammation.

Overcoming clinical inertia to achieve blood pressure goals: the role of fixed-dose combination therapy

The treatment of hypertension should cause blood pressure (BP) changes that reduce the long-term risks of cardiovascular morbidity and mortality. There are considerable clinical benefits to be gained by promptly treating patients to recognized BP goals, particularly for those at high risk. This may be achieved by the use of combination therapy as first-line treatment. However, despite widely acknowledged therapeutic guidelines, there are significant gaps between current treatment recommendations and their implementation in clinical practice. One important explanation for inadequate treatment and subsequent poor BP control is clinical inertia. Undertreatment and clinical inertia may sometimes be mistaken for treatment-resistant hypertension, as is often the case in specific patient populations whose disease is often considered a challenge to treat because of a greater risk of cardiovascular complications (e.g. Blacks, obese patients, and those with diabetes). The availability of fixed-dose drug combinations may address some of the common misconceptions thought to promote clinical inertia. Few studies have specifically focused on subpopulations with difficult-to-treat hypertension that is uncontrolled on monotherapies. One example is an ongoing 20-week, multicenter, prospective, blinded endpoint, dose-titration, treat-to-goal study evaluating the efficacy and safety of initial fixed-dose combination therapy with amlodipine/olmesartan medoxomil, and further up-titration with hydrochlorothiazide, in patients with hypertension who are uncontrolled on antihypertensive monotherapy. This study may demonstrate the benefits of treating patients with hypertension to goal using initial fixed-dose combination therapy, even in patients considered to be at a higher risk of cardiovascular complications.

Mean platelet volume in patients with dipper and non-dipper hypertension

Patients with non-dipper hypertension are known to carry a high risk of cardiovascular complications. In this study, we hypothesized that non-dippers may be associated with platelet dysfunction and it can be determined by mean platelet volume (MPV). A total of 216 outpatients treated with antihypertensive drugs for at least 6 months were enrolled. Dipper and non-dipper patterns were detected and clinical, laboratory and ambulatory blood pressure recording data were matched between non-dipping and dipping groups. MPV was significantly higher in patients in non-dipping than dipping groups (p<0.001). In correlation analyses, MPV was negatively correlated with the rate of systolic and diastolic fall at night (p<0.001, r=−0.46) and (p<0.001, r=−0.43), respectively. Also MPV was correlated with nocturnal pulse pressure (p=0.001, r=0.22). Other variables were similar between non-dipping and dipping groups. The present study showed that MPV is higher in non-dipping than dipping hypertensive patients. Platelet activation or dysfunction probably is an alternative mechanism for increasing cardiovascular events in non-dippers.

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management

Liver transplantation is the standard of care for acute and chronic causes of end-stage liver disease. Advances in medical therapy and surgical techniques have led to improvement of patient and graft survival rates following orthotopic liver transplantation. However, the prevalence of post-transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. To determine the incidences, risk factors, and treatment for hypertension, hyperlipidaemia, diabetes, and obesity in the post-liver transplantation population. We performed a review of relevant studies available on the PubMed database that provided information on the incidence, risk factors and treatment for cardiovascular complications that develop in the post-liver transplantation population. Current immunosuppressive agents have improved patient and graft survival rates. However, long-term exposure to these agents has been associated with development of systemic and metabolic complications including hypertension, hyperlipidaemia, diabetes mellitus and obesity. Cardiovascular disease remains one of the most common causes of death in liver transplant patients with functional grafts. Liver transplant recipients have a higher risk of cardiovascular complications compared with the nontransplant population. Post-transplant cardiac risk stratification and aggressive treatment of cardiovascular complications, including modification of risk factors and tailoring of immunosuppressive regimen, is imperative to prevent serious complications.

SAFARI - RANDOMISED TRIAL ON COMPLEX THERAPY OF ARTERIAL HYPERTENSION AND DISLIPIDEMY. THE MAIN RESULTS

Aim. To evaluate possibility of complex pharmaceutical effect simultaneously on 2 risk factors – arterial hypertension (HT) and hypercholesterolemia (HH) in patients with high risk of cardiovascular complications (CVC). Material and methods. 101 patients with HT of 1-2 stage, HH and high risk of CVC (SCORE&gt;5) were included in the study. Patients were randomized in 2 groups: active therapy group (ATG) and control group (CG). ATG patients were actively treated for HT and HH control. The long-acting nifedipine (Nifecard XL, LEK) 30 mg once daily (OD) was prescribed as start antihypertensive drug. Hydrochlorothiazide 12,5 mg/day OD and bisiprolol 5 mg OD was added if antihypertensive effect was insufficient. Atorvastatin (Tulip, LEK) 20-40 mg OD was prescribed for HH control. Management of CG patients was performed by doctors of out-patient clinics. The study duration was 12 weeks. Results. Systolic and diastolic blood pressure (BP) levels in ATG patients were lower than these in CG patients. Target BP level was reached in 88,4% of ATG patients and only in 48,9% of CG patients. Cholesterol of low density lipoprotein (CH LPLD) level was also lower in ATG patients than this in CG patients. Target CH LPLD level was reached in 37,2 % of ATG patients and in 8,3 % of CG patients. Relative risk of CVC was significantly lower in ATG patients than this in CG patients. Conclusion. SAFARI trial shows that effective pharmaceutical simultaneous control of 2 key risk factors, HT and HH, results in risk reduction of CVC.

In Vitro Inhibition of Platelet Aggregation in Response to Increasing Concentrations of Tirofiban in Patients with Significant Renal Insufficiency

Patients with impaired renal function are a growing subset at higher risk for cardiovascular complications due to vasculopathic state, inducing accelerated atherosclerosis and arteriosclerosis. These patients are at increased risk for complications after coronary interventions, especially major bleeding events. As a result, this at-risk population of patients has not been well studied in most of the major clinical trials evaluating coronary interventions. Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors in the setting of acute myocardial infarction. In this study, we attempted to find the in vitro concentration of tirofiban required to inhibit platelet aggregation to <10% in patients with moderate to severe renal insufficiency. A total of 21 patients were divided into two groups based on estimated creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma from each subject was then incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was used to assess the degree of platelet aggregation in response to adenosine diphosphate (ADP). Patients in group 1 had a baseline platelet aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min had an average platelet aggregation inhibition of 12% with 50ng/ml of tirofiban.We found a significant decrease in platelet aggregation in group 2 at 25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1. Our data indicate that patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.We suggest further clinical trials to define an objective means to calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these patients to prevent potentially fatal complication of major hemorrhagic events.

Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function

OBJECTIVE— Glycemic control decreases the incidence and progression of diabetic complications but increases the incidence of hypoglycemia. Hypoglycemia can impair hormonal and autonomic responses to subsequent hypoglycemia. Intensive glycemic control may increase mortality in individuals with type 2 diabetes at high risk for cardiovascular complications. We tested the hypothesis that prior exposure to hypoglycemia leads to impaired cardiovascular autonomic function.RESEARCH DESIGN AND METHODS— Twenty healthy subjects (age 28 ± 2 years; 10 men) participated in two 3-day inpatient visits, separated by 1–3 months. Autonomic testing was performed on days 1 and 3 to measure sympathetic, parasympathetic, and baroreflex function. A 2-h hyperinsulinemic [hypoglycemic (2.8 mmol/l) or euglycemic (5.0 mmol/l)] clamp was performed in the morning and in the afternoon of day 2.RESULTS— Comparison of the day 3 autonomic measurements demonstrated that antecedent hypoglycemia leads to 1) reduced baroreflex sensitivity (16.7 ± 1.8 vs. 13.8 ± 1.4 ms/mmHg, P = 0.03); 2) decreased muscle sympathetic nerve activity response to transient nitroprusside-induced hypotension (53.3 ± 3.7 vs. 40.1 ± 2.7 bursts/min, P < 0.01); and 3) reduced (P < 0.001) plasma norepinephrine response to lower body negative pressure (3.0 ± 0.3 vs. 2.0 ± 0.2 nmol/l at −40 mmHg).CONCLUSIONS— Baroreflex sensitivity and the sympathetic response to hypotensive stress are attenuated after antecedent hypoglycemia. Because impaired autonomic function, including decreased cardiac vagal baroreflex sensitivity, may contribute directly to mortality in diabetes and cardiovascular disease, our findings raise new concerns regarding the consequences of hypoglycemia.

Testing at home--the screening of the future?

Cardiovascular diseases (CVD) and diabetes mellitus (DM) are major public health concerns in modern society. Although mortality from CVD has decreased substantially in many European countries in the past 30 years due to better prevention (e.g. encouraging people to stop smoking and discouraging people from starting) and better medicinal treatment, CVD remains the category of diseases with the highest number of life-years lost. Due to sedentary lifestyles and unfavourable nutrition habits, obesity has developed into a new ‘epidemic’ with adverse consequences for CVD and DM. Type 2 diabetes is associated with a high risk of cardiovascular complications and mortality, with a 4-fold increased risk of dying from CVD compared to non-diabetic counterparts.1 Type 2 diabetes is now estimated to cause 1 million deaths per year worldwide. Randomized and controlled treatment trials have shown that reducing weight and treating glucose levels in diabetic patients is effective in reducing the complications of disease.2 An important question, however, is whether we can and, if so, whether we should take more effective measures at an earlier stage of the natural progression of disease. A …

Practical Assessment of Maternal Cardiovascular Risk in Pregnancy

Cardiovascular disease in pregnancy is the most common cause of maternal mortality in the developed world and an important cause of heart failure, stroke, and arrhythmia. As more children with congenital heart disease survive into adulthood, there is a more pressing need to understand the risks that pregnancy poses for these women. Pregnancy, labor, and delivery increase the hemodynamic stress on the cardiovascular system and place women with heart disease at increased risk of cardiovascular complications, which include heart failure and death. Systematic assessment of pregnancy risk in these women, ideally before conception, is essential in optimizing maternal and fetal outcomes. This article describes the process of assessing risk of pregnancy-associated cardiovascular complications in women with structural heart disease. We review the current literature on pregnancy risk in women with complex congenital lesions, valvular heart disease, cardiomyopathy, and aortopathy, and suggest an approach to risk stratification. Based on a review of the literature, we report features that pose an increased risk of adverse maternal and fetal outcomes, which include poor maternal functional status; prior history of heart failure, arrhythmia, or cerebral vascular events; cyanosis; poor systemic ventricular function; and severe aortic or mitral stenosis. Pulmonary hypertension and Eisenmenger syndrome place women at exceedingly high risk for cardiovascular complications in pregnancy, including maternal and fetal death.

Anaesthesia and morbid obesity

The prevalence of morbid obesity is increasing in the UK. Recent UK government statistics suggest that 20% of adults are obese and 1% morbidly obese. Anaesthesia and surgery may entail considerable risk for obese patients. Obesity is a multi-system disorder, particularly involving the respiratory and cardiovascular systems; therefore, a multidisciplinary approach is required. This article presents a broad overview of the pathophysiological and practical considerations for anaesthetizing such patients for major (non-bariatric) surgery. A body mass index (BMI) of .35 kg m with associated comorbidity, or .40 kg m without significant comorbidity, is considered to be morbidly obese; .55 kg m is considered super-morbidly obese (Table 1). However, morbidity and mortality increase sharply when BMI is .30 kg m, particularly in smokers, and risk is proportional to duration of obesity. For a given BMI, men are at higher risk of cardiovascular complications than women. Obesity is described classically as conforming to an android or gynaecoid fat distribution (‘apples and pears’). Both the actual BMI of a particular patient and the distribution of fat are important considerations. The gynaecoid fat distribution characteristically involves more fat distributed in peripheral, sites (arms, legs, and buttocks). An android fat distribution involves more central fat (intraperitoneal fat, including involvement of the liver and omentum). Specific definitions have been proposed based on the waist-to-hip ratio. A value .0.8 in women or 1.0 in men is typical of the android distribution. Although the android distribution predominates in males and is associated with a higher risk of morbidity, either distribution can occur in each gender. Weight loss reduces risk for both groups. Obese people have greater energy expenditure than lean individuals, and this is balanced by increased caloric intake. Basal metabolic rate is ‘normal’ in obese individuals when corrected for body surface area. However, with increasing weight, body surface area increases and hence absolute basal metabolic rate values are higher than in lean individuals. Consequently, there is a greater absolute oxygen consumption and carbon dioxide production.

Preoperative Evaluation of the Gynecologic Patient

The preoperative evaluation serves several purposes for the gynecologist. Patients with previously undiagnosed, or incompletely managed, medical concerns are identified and appropriate treatment initiated. In women with known medical concerns, the surgeon can anticipate problems and plan for appropriate postoperative care. In certain cases, the preoperative evaluation identifies medical conditions that are unstable enough to adversely affect the postoperative outcome, and appropriate referral for medical management can be made. One of the most important aspects of the evaluation is the identification of women at high risk for cardiovascular complications. A stepwise approach is useful to identify those women who may proceed to surgery and those who need further testing. Much of the preoperative evaluation of the woman with pulmonary disease can be done during the history and physical examination without additional testing. Deep venous thrombosis is a significant concern in gynecologic surgery; appropriate identification of the woman at risk is important, with initiation of prophylaxis occurring shortly after the surgery concludes. Many women undergoing gynecologic surgery have diabetes. Careful management of diabetes in the perioperative period has become more germane, with evidence of improved outcomes as tight control is achieved. Much of the preoperative evaluation falls easily into the purview of the gynecologist, with advice presented as to when medical consultation should be considered.

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes

Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.

Prevalence and Prognostic Influence of Peripheral Arterial Disease in Patients ≥40 Years Old Admitted into Hospital Following an Acute Coronary Event

Objective A significant proportion of patients with ischemic heart disease have associated peripheral arterial disease (PAD), but many are asymptomatic and this condition remains underdiagnosed. We aimed to study the prevalence of PAD in patients with an acute coronary syndrome (ACS) and to evaluate its influence in hospital clinical outcomes. Methods The PAMISCA register is a prospective, multicenter study involving patients ≥40 years old with ACS admitted to selected Spanish hospitals. All patients had their ankle-brachial index (ABI) measured between days 3 and 7 after the ischemic event. Results 1410 ACS patients (71.4% male) were included. PAD determined by ABI was documented in 561 patients (39.8%). Factors independently related to PAD were age (OR: 1.04; 95% CI: 1.03–1.06; p < 0.001), smoking (OR: 1.88; 95% CI: 1.41–2.49; p < 0.0001), diabetes (OR: 1.30; 95% CI: 1.02–1.65; p < 0.05), previous cardiac disease (OR: 1.54; 95% CI: 1.22–1.95; p < 0.001) and previous cerebrovascular disease (OR: 1.90; 95% CI: 1.28–2.80; p < 0.001). Following the ACS, an ABI ≤ 0.90 was associated with increased cardiovascular mortality (OR: 5.45; 95% CI: 1.16–25.59; p < 0.05) and a higher risk of cardiovascular complications. Conclusion The prevalence of PAD in patients ≥40 years presenting with ACS is high and it is associated with increased cardiovascular risk.

High-sensitivity C-reactive protein levels in HIV-infected patients treated or not with antiretroviral drugs and their correlation with factors related to cardiovascular risk and HIV infection

Aims To compare high-sensitivity C-reactive protein (hsCRP) in HIV-infected patients treated or not with antiretroviral (ARV) drugs and to correlate hsCRP levels with traditional cardiovascular risk factors and parameters of HIV infection. Methods One hundred and seventy-one HIV-infected patients were included (129 ARV-treated and 42 ARV-naïve). Evaluations included anthropometric measurements, blood pressure, laboratory tests, ultrasonographic measurement of fat thickness and impedance analysis. Results hsCRP levels were higher in ARV-treated compared to ARV-naïve patients ( p < 0.001). Seventy-two (56%) ARV-treated patients and 11 (26%) ARV-naïve patients had hsCRP concentrations >3 mg/dl (high risk for cardiovascular complications) (OR 3.56; 95%CI: 1.55–8.29; p = 0.001, χ 2 test). hsCRP levels correlated positively with waist measurement ( p = 0.004), waist-to-hip ratio ( p < 0.001), systolic ( p = 0.05) and diastolic ( p = 0.03) blood pressure, intra-abdominal fat thickness ( p = 0.02), triglycerides ( p = 0.001), total cholesterol ( p = 0.01), fasting glucose ( p = 0.01), and glucose ( p < 0.001) and insulin levels ( p = 0.02) measured 2 h after load. No correlation was found between hsCRP levels and CD4 cell counts and HIV-viral load. Independent factors associated with hsCRP levels were therapy with current non-nucleoside reverse transcriptase inhibitors (NNRTI) ( p = 0.003), waist-to-hip ratio ( p = 0.006), fasting glucose ( p = 0.049) and glucose levels 2 h after load ( p = 0.003) in multivariate analysis model 1 and current NNRTI therapy ( p < 0.001), protease inhibitor therapy ( p = 0.016) and cardiometabolic syndrome ( p = 0.022) in multivariate analysis model 2. Conclusion hsCRP in HIV-infected patients is associated with traditional cardiovascular risk factors, principally in ARV-treated patients. hsCRP levels are not associated with CD4 cell counts and HIV-viral load and may constitute a marker for cardiovascular risk related to HIV infection and ARV therapy.

Coronary in-stent restenosis in diabetic patients after implantation of sirolimus or paclitaxel drug-eluting coronary stents

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0 ± 3.4 months [mean ± 1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66 ± 10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA 1c in patients with restenosis was 7.6 ± 1.8%. There was no difference in the rate of restenosis with sirolimus – ( n = 8) compared with paclitaxel – ( n = 9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.

How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification

The inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg of aspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5-20 microM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (>5 Omega after 6 minutes, aggregation index >65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y(12)-ADP receptor antagonist 2-MeS-AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y(12) was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily). Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer-guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%. This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.