Absence Of Traditional Risk Factors Research Articles

Skin and soft tissue infections in the intensive care unit: a retrospective study in a tertiary care center.

ObjectiveTo identify factors that may influence outcomes in patients with severe skin and soft tissue infections in the intensive care unit.MethodsA retrospective observational study was conducted in a cohort of 1,123 critically ill patients admitted to an intensive care unit with a primary or secondary diagnosis of severe skin and soft tissues infection between January 2006 and December 2014.ResultsThirty patients were included, 20 (66.7%) of whom were diagnosed with necrotizing fasciitis; in these patients, perineal area involvement was most commonly identified. Abscess was diagnosed in 8 (26.7%) patients, most commonly involving the cervical area. Risk factors such as immunosuppression and previous surgical trauma were commonly observed in this population. The most commonly isolated microorganism was Escherichia coli. Multidrug resistant microorganisms were commonly detected, even in the absence of traditional risk factors; among these patients, previous use of antibiotics was the most common risk factor for drug resistance. The rate of mortality was significantly higher in patients with necrotizing fasciitis (55%, p = 0.035) and associated with disease severity, presence of septic shock, cardiac arrest and leucocytosis.ConclusionDifferent risk factors and etiologies of severe skin and soft tissue infections were identified. Necrotizing fasciitis and drug-resistant bacteria were significant predictors of mortality, even in the absence of traditional risk factors. Obtaining a better understanding of trends in the risk factors and microorganisms associated with severe skin infections may help in the determination of prompt treatment and antibiotic choices.

Inflammation and thrombosis - testing the hypothesis with anti-inflammatory drug trials.

The hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammation-related plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.

Abstract 17973: Clinical Markers Associated With Subclinical Atherosclerosis in Otherwise Apparently Healthy Young Adults

Introduction: Traditional risk factors are poor predictors of cardiovascular events in younger adults. Considering the long silent evolution of atherosclerosis beginning in younger adulthood before the appearance of clinical events at a more advanced age, a simple tool to predict early atherosclerosis in young adults would be desirable to guide primordial prevention. An altered cardiometabolic profile is associated with increased cardiovascular disease in older adults independent from traditional risk factors, but the value of this profile in an otherwise healthy young adult population is unknown. Hypothesis: Cardiometabolic risk markers would be associated with early atherosclerosis in young adults despite the absence of traditional risk factors. Methods: Healthy young adults (18-35 years) devoid of cardiovascular risk factors (diabetes, smoking, hypertension, dyslipidemia) and obesity were prospectively enrolled. Anthropometric measurements, ECG, lipid profile, fasting blood glucose, blood pressure and high-resolution carotid artery MRI were realized. Results: Although the 240 participants (25.8 years, SEM=0.29, 48% women) were at low risk for atherosclerosis, we identified atherosclerosis in 72.6% of men and 64.7% of women (p=0.19). Males had greater atherosclerosis burden vs. females (carotid wall volume [CWV]: 1817 mm3/48mm, SEM=29.7 vs. 1579 mm3/48mm, SEM=21.2; p<0.0001). By multivariate analysis, atherosclerosis burden was associated with fasting blood glucose (p=0.01), BMI (p=0.01), and waist circumference (p<0.001), the latter having the strongest correlation with atherosclerosis burden (r=0.41, p<0.0001). ROC analyses established cutoffs for waist circumference identifying greater atherosclerosis burden in apparently healthy young adults. Conclusion: A simple low-cost office-based tool, waist circumference measurement improves prediction of early atherosclerosis in otherwise apparently healthy young adults.

CARDIOMETABOLIC RISK FACTORS ASSOCIATED WITH SUBCLINICAL ATHEROSCLEROSIS IN APPARENTLY HEALTHY YOUNG ADULTS

Atherosclerosis is a leading cause of morbidity and mortality in developed and developing regions, resulting to overt vascular disease in the later decades of life. Nonetheless, the first signs of atherosclerosis have been identified in up to 78% of healthy young adults at autopsy, indicating that the needed conditions for disease development are present long before the appearance of traditional risk factors. We sought to determine whether and to what degree atherosclerosis is present in apparently healthy young adults devoid of traditional cardiovascular risk factors and obesity, and we investigated the associations of cardiometabolic risk markers with early atherosclerosis burden in this population. Young Caucasian adults (18-36 years) devoid of traditional cardiovascular risk factors and obesity, and no history of chronic medication use or disease were assessed for cardiometabolic risk markers. Subcutaneous abdominal adipose tissue (SAT), ectopic fat depots (visceral abdominal adipose tissue [VAT], epicardial adipose tissue [EAT], and hepatic fat fraction [HFF]), as well as carotid artery wall volumes (CAWV) were measured by magnetic resonance imaging. According to cardiometabolic profile, the 240 participants (25.8 ± 4.5 years; 48% women) had a low-risk for atherosclerosis. However, premature atherosclerosis was present in 68.8% of the population with no difference between prevalence in both sexes although the burden was significantly greater in men vs. women (CAWV: 1817 ± 330 vs. 1579 ± 228 mm3/48mm, p<0.0001). Men possessed lesser SAT volume than women, while they presented higher EAT and VAT volumes compared to women. HFF was similar between men and women. CAWV increased progressively with the accumulation of VAT and EAT. Early atherosclerosis was associated with apolipoprotein B/apolipoprotein A-1 ratio, fasting blood glucose, waist circumference and EAT volume, but waist circumference was the strongest marker independently associated with atherosclerosis burden. In addition, “high-normal” levels of risk factors commonly used (≥50th percentile), especially when clustering, are associated with greater atherosclerosis burden in this population. Subclinical atherosclerosis is present in more than half of all apparently healthy young adults despite the absence of traditional cardiovascular risk factors and obesity. Waist circumference is the strongest predictor of atherosclerosis burden in both males and females of our cohort. Our findings suggest routine waist circumference measurement may help identify risk of premature atherosclerosis in apparently healthy young men and women in the absence of traditional risk factors.

You Are as Old as Your Arteries ‐ And Microvessels

Nearly four centuries ago the famous English physician Thomas Sydenham (1624‐1689) commented that “a man is as old as his arteries.” Cardiovascular diseases are the indeed most common cause of death among the elderly patients in the Western world. It is becoming evident that aging results in well‐defined phenotypic changes, which render the cardiovascular system prone to disease even in the absence of traditional risk factors. The consequences of vascular aging range from myocardial infarction through erectile dysfunction to stroke. In addition to its deleterious effects on large arteries aging also results in functional and phenotypic alterations at the level of the microcirculation. There is increasing evidence that age‐related microvascular impairment plays a critical role in the pathogenesis of vascular cognitive impairment (VCI). The potential roles of microvascular mechanisms involved in VCI, including microvascular rarefaction and disruption of the blood‐brain barrier will be discussed. Also, moment‐to‐moment adjustment of cerebral blood flow via neurovascular coupling is essential for the maintenance of normal neuronal function. Increased oxidative stress that occurs with aging was shown to impair neurovascular coupling, which likely contributes to a significant age‐related decline in higher cortical function, increasing the risk for VCI. There are suggestions in the literature and new data will be presented that in aged laboratory rodents neurovascular coupling and endothelium‐dependent cerebromicrovascular dilation can be rescued, which represents a potential therapeutic target for the promotion of healthy brain aging.

Inflammatory bowel disease as a risk factor for premature coronary artery disease.

BackgroundCrohn’s disease and ulcerative colitis are both systemic chronic diseases that alter bowel physiology. The central process in inflammatory bowel disease (IBD) and the associated manifestations are the result of B-cell production of IgG autoantibodies directed against self-antigens in various organ systems including coronary endothelium. Previous studies have demonstrated significant micro-vascular endothelial dysfunction in patients with IBD compared to patients not affected by the disease. We sought to analyze the relation, if any, between IBD and the development of premature coronary artery disease (CAD).MethodsWe queried our hospital database to find IBD patients admitted to the hospital from January 1, 2007 to December 31, 2008. Patients with traditional cardiovascular (CV) disease risk factors including hypertension, congestive heart failure (CHF), diabetes, age ≥ 65, hyperlipidemia, family history, end-stage renal disease (ESRD), and greater than five pack-year smoking history were excluded from the study cohort. The charts of the remaining 300 patients with diagnosed IBD were then analyzed for the incidence of CV disease events including acute myocardial infarction (MI), unstable angina, positive stress testing, and any cardiac intervention including coronary angioplasty and/or intracoronary stent implantation.ResultsOf the 300 patients included, only one patient had a CV disease event. This patient had a positive exercise stress thallium test. Otherwise, the remaining 299 patients (99.7%) did not have any reported CV disease events over the 2-year follow-up period.ConclusionMost of the clinical sequelae of CV disease events are the result of inflammatory changes at the vascular level. While IBD is associated with a chronic inflammatory state as reflected by high sedimentation rates, C-reactive protein (CRP), homocysteine levels, etc., our data seem to indicate that chronic inflammation in the absence of traditional risk factors is not associated with an increased risk of premature CV disease events. More wide-scale prospective studies should be performed to elucidate the relationship, if any, between chronic inflammation and CV disease risk.

Relationship of Microalbuminurea in Non-Diabetic and Non-Hypertensive Patients with Acute Myocardial Infarction

Background and objective: Microalbuminuria (MA) has implications on the development of CHD and it is emerging as a new risk factor of this disease. The aim of the present study was to assess the prevalence of microalbuminuria in non-diabetic and non-hypertensive subjects suffering from acute myocardial infarction, short term outcome and its prognostic importance as indicator of cardiovascular morbidity and mortality. To evaluate the relationship between Microalbuminuria and Acute Myocardial Infarction in Non-diabetic and non- hypertensive patients admitted in CCU Cardiology Department LUMHS Hyderabad. Material and methods: A cross-sectional and hospital based study. 126 consecutivenon diabetic non hypertensive patients of acute myocardial infarction were included in this study. Microalbuminuria was determined by immunoturbedimeteric method. Serum glucose and urea were measured by enzymatic method. Serum creatinine was measured by kinetic colorimetric method. Results: A significant Microalbuminuria was found in patients of AMI who were non diabetic and non-hypertensive. The mortality and morbidity in short term outcome was also significantly increased in patients having MA, indicating the significance of Microalbuminuria as powerful prognostic biomarker. Conclusion: Microalbuminuria may have an association with acute myocardial infarction in absence of traditional risk factors like Diabetes and Hypertension.

Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study.

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.

Risk of coronary heart disease associated with metabolic syndrome and its individual components in Iranian subjects: a matched cohort study.

To evaluate the risk of coronary heart disease (CHD) associated with metabolic syndrome (MetS) and its individual components in a representative sample of diabetic and nondiabetic Iranians. Moreover, we aimed to define the most hazardous MetS components. Two cohorts consisting of 1737 nondiabetic and 2385 diabetic participants were followed for the first CHD event during 8.5 years (until December 2013). MetS is defined as having 3 individual components associated with increased risk of CHD (hazard ratio [HR] for MetS: in the unadjusted were 2.85 [2.27-3.57] and in the fully adjusted model 1.80 [1.42-2.28]). MetS was associated with lower hazard of CHD in subjects older than 65 (HR: 1.50 vs. 3.47; P for interaction < .05) and in men (HR: 1.68 vs. 4.87; P for interaction < .05). Presence of 4 of 5 individual MetS components increased the risk of CHD associated with MetS as a constellation. The value of MetS is augmented in the presence of low high-density lipoprotein-cholesterol (HR: 5.74 [2.52-13.08]) versus its absence (HR 1.91 [1.33-2.75]), high triglycerides (HR: 3.39 [1.38-8.34] vs. 1.99 [1.40-2.82] in its absence) and elevated blood pressure (HR: 2.61 [1.43-4.76] vs. 1.80 [1.26-2.58] in its absence). We address the value of MetS components in the prediction of CHD and in the absence of traditional risk factors. This study provides evidence for the synergistic effect of MetS components on the incidence of CHD.

Nondaily smoking: a population-based, longitudinal study of stability and predictors

BackgroundNondaily smoking appears to have remained stable in Western countries in recent years, alongside a steep decline in daily smoking. Nondaily smoking increases the risk of several diseases and premature mortality, but our knowledge about nondaily smoking is limited. The present study was designed to examine the stability of nondaily smoking during young adulthood, and to identify adolescent factors predictive of nondaily smoking compared with nonsmoking and non-nicotine-dependent and nicotine-dependent daily smoking.MethodsA population-based sample (n = 942) of Norwegians was followed up by surveys for 13 years, from adolescence to young adulthood. Information about smoking patterns, nicotine dependence, school achievement, parents’ and peers’ smoking, and parental monitoring was collected. Data on parental and participants’ education were obtained from a national register.ResultsOf all nondaily smokers at age 21 years, 26% were still nondaily smokers at 27 years, while 17% had become daily smokers and 57% had quit. Bivariate analyses revealed that young adult nondaily smokers did not differ from nonsmokers on any of the included variables, while a number of differences in parental, peers’ and individual characteristics were observed between nondaily smokers and the two categories of smokers in young adulthood. Longitudinal analyses revealed that unorganized leisure time activities and peers’ smoking differentiated nondaily smoking from nonsmoking. Higher educational achievement and less parental binge drinking predicted nondaily smoking and differentiated it from both categories of daily smoking.ConclusionsThe degree of nondaily smoking-stability from 21 to 27 years of age was modest, and most nondaily smokers quit smoking in the course of young adulthood. Young adult nondaily smokers were quite similar to nonsmokers, but differed substantially from both nicotine-dependent and nondependent daily smokers. The study suggests that nondaily smoking—at least in the absence of traditional risk factors for smoking—is usually a transitory behavior, with most people returning to nonsmoking.

Ventilator-associated pneumonia after elective cardiac surgery caused by Pneumocystis jirovecii

Ventilator-associated pneumonia is a severe complication among patients undergoing cardiac surgery. Although hospital-acquired bacterial pathogens, often multidrug resistant, are the most frequent cause, non-bacterial atypical and opportunistic agents traditionally associated with immunocompromise are increasingly recognized. We describe ventilator-associated pneumonia due to Pneumocystis jirovecii in the absence of traditional risk factors for Pneumocystis pneumonia in a patient after cardiac surgery.

Vasculitides as a rare cause of intermittent claudication

Intermittent claudication of the lower extremities is a common symptom described in older patients with atherosclerotic peripheral arterial disease. Peripheral arterial disease due to atherosclerosis is known to be associated with a higher risk of myocardial infarction, stroke and all-cause mortality. However, if intermittent claudication appears in a younger group of patients or older patients in absence of traditional risk factors for atherosclerosis such as smoking, dyslipidemia, arterial hypertension and diabetes mellitus other causes than atherosclerosis must be considered. These conditions include vasculitides, fibromuscular dysplasia, cystic adventitial disease, excentric vascular compression by tumor, popliteal artery entrapment syndrome, trauma or dissection. Vasculitides present a heterogenous group of disorders characterized by inflammatory destruction of blood vessels. Although often not a leading symptom intermittent claudication could be a part of a clinical picture in giant-cell arteritis, Takayasu´s arteritis, Buerger´s disease, polyarteritis nodosa or Behçet disease. Limb claudication is usually of rapid onset, progressive and bilateral. Each of the mentioned vasculitides is specific in ethiology and clinical manifestation with a variable prognosis for the patient. Increased awareness of the presence of different causes of limb claudication and their early diagnosis with a prompt initiation of appropriate treatment may help to avoid clinical progression that can lead to vascular surgery or even limb loss (Ref. 37).

Early Atherosclerosis in Rheumatoid Arthritis: A case Control Study

BACKGROUND: Atherosclerosis remains the major cause of death and premature disability in developed countries.&#x0D; OBJECTIVES: To assess the prevalence of early (accelerated) atherosclerosis in Rheumatoid Arthritis (RA) patients in the absence of traditional risk factors and influence of various other parameters on it.&#x0D; METHODS: The study was carried at a tertiary care university hospital in northern India (Kashmir) in year 2008-2009. Thirty nine patients in the age group of 25- 55 years with RA fulfilling the American College of Rheumatology (ACR) Modified criteria 1987 and a purposive sample of twenty healthy volunteers that served as controls were enrolled to judge any difference in the studied parameters. Subjects with other risk factors for atherosclerosis were excluded from the study. Disease Activity Score (DAS-28) was used to measure the disease activity. B-mode ultrasonography was used to measure carotid artery intima media thickness (CIMT) in both the groups.&#x0D; RESULTS: RA patients presented with elevated CIMT in the age group of 41-50 years (p = 0.665) whereas volunteers had such tendency in the 5th decade of life (p = 0.550). Duration of disease greater than 5 years also positively influenced the development of increased CIMT in the patient group (p 0.64).Patients in the RA group had a higher erythrocyte sedimentation rate (ESR) and mean CIMT as compared to the controls(p = 0.000). RA patients had lower hemoglobin concentration when compared to age and sex matched controls. Intergroup comparison in patients with normal and increased CIMT showed that increased BMI, elevated triglyceride (TG) concentration and raised ESR influenced the development of CIMT which on binary logistic regression showed that TG (p = 0.043) and BMI (p = 0.053) had influence in progression of CIMT.&#x0D; CONCLUSION: Rheumatoid Arthritis patients have definite evidence of early (accelerated) atherosclerosis due to inflammation even in this ethnic population. BMI and serum triglycerides even in normal range have noteworthy influence in acceleration of atherosclerosis in them. B-mode ultrasonography is simple, non-invasive, and one of the sensitive methods to detect earlier atherosclerotic changes in them. JMS 2012;15(2):106-110

Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes

Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demonstrated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy.

Inflammation in Atherosclerosis

Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances.

DELAYED CONTRAST ENHANCEMENT ON CARDIAC MRI AND RISK OF CLINICALLY SIGNIFICANT VENTRICULAR ARRHYTHMIAS IN HYPERTROPHIC CARDIOMYOPATHY: A META-ANALYSIS OF OBSERVATIONAL STUDIES

A small proportion of patients with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death (SCD) despite the absence of traditional risk factors. Therefore, additional predictors of SCD need to be identified. Delayed contrast enhancement (DCE) on cardiac magnetic resonance imaging (MRI)

Clinical Outcomes and Treatment After Drug-Eluting Stent Failure

The optimal percutaneous treatment of drug-eluting stent (DES) in-stent restenosis (ISR) and the correlates for recurrent DES ISR remain unclear. From 2003 to 2008, 563 patients presenting with recurrent symptoms of ischemia and angiographic ISR after DES implantation were included. Of these, 327 were treated with re-DES (58.1%), 132 underwent vascular brachytherapy (23.4%), and 104 were treated with conventional balloon angioplasty (18.5%). Variables associated with target lesion revascularization at 1 year were explored by individual proportional hazard models. This population presents a high prevalence of comorbidities, including diabetes (43.7%), previous myocardial infarction (MI) (45.8%), coronary bypass graft surgery (39.2%), chronic renal failure (18.8%), and heart failure (17.3%). Baseline clinical characteristics were balanced among the 3 groups; however, patients undergoing vascular brachytherapy presented with more complex lesions and a higher prevalence of prior stent/vascular brachytherapy failure than did the rest of the population. The overall incidence of recurrent DES failure at 1-year follow-up was 12.2%, which was similar among the 3 groups (P=0.41). The rate of the composite end point (death, Q-wave-MI and target lesion revascularization) at 1-year follow-up was 14.1% for re-DES, 17.5% for vascular brachytherapy, and 18.0% for conventional balloon angioplasty (P=0.57). After univariable analysis tested the traditional known covariates related to ISR, none of them were associated with repeat target lesion revascularization. Recurrence of ISR after DES treatment failure is neither infrequent nor benign, and optimal therapy remains unclear and challenging. Given the absence of traditional risk factors for ISR in this population, further research is required to elucidate both the correlates involved in DES ISR and the optimal treatment for this condition.

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.

Association between polymorphisms of the renin angiotensin system and carotid stenosis

Carotid stenosis is a common manifestation of systemic atherosclerosis. Apart from traditional risk factors, genetic determinants, such as polymorphisms of the renin angiotensin system (RAS), may be relevant in modulating the atherosclerotic process leading to carotid stenosis. In this study, we investigated the role of angiotensin-converting enzyme (ACE) I/D and -240A>T, angiotensinogen (AGT) M235T, and angiotensin type 1 receptor (AGTR1) 1166A > C polymorphisms in modulating the susceptibility to the disease. Eight hundred twenty-one consecutive patients with severe carotid stenosis (≥70%) and 847 control subjects were investigated. A significant difference in genotype distribution (P < .0001) and allele frequency (P < .0001) between patients and controls for the ACE I/D polymorphism, but not for the other single-nucleotide polymorphisms investigated, was observed. The ACE D allele frequency was significantly higher in patients without traditional risk factors in comparison with that observed in those with at least one risk factor (0.71 vs 0.61; P = .04). The ACE D allele significantly influenced carotid stenosis under dominant, recessive, and additive model of inheritance at both univariate (P < .0001) and multivariate analysis (P < .0001). When the combined effect of RAS unfavorable alleles was considered, patients carrying less than three alleles had a lower risk of carotid stenosis (odds ratio [OR], 0.79 [0.63-0.99]; P = .05), while carriers of more than four unfavorable alleles had an increased risk (OR, 1.44 [1.12-1.84]; P = .004), in comparison with subjects carrying three or four unfavorable alleles. ACE D allele frequency was similar in patients with and without additional atherosclerotic localizations (0.61 vs 0.62, respectively). Our findings evidence a role for ACE I/D polymorphism in influencing the susceptibility to carotid stenosis, even in the absence of traditional risk factors. Interestingly, our findings provided further information concerning the role of this polymorphism in modulating the atherosclerotic process apart from its different localizations.

Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. A comprehensive survey.

Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. A comprehensive survey.