Atherosclerotic cardiovascular disease

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Doctors' knowledge, attitudes, and compliance with 2013 ACC/AHA guidelines for prevention of atherosclerotic cardiovascular disease in Singapore

Doctors' knowledge, attitudes, and compliance with 2013 ACC/AHA guidelines for prevention of atherosclerotic cardiovascular disease in Singapore

Conclusion: Although embracing the 2013 ACC/AHA guidelines in clinical practice is expected to provide better clinical care to patients, our study revealed high reluctance by physi- cians, especially in the use of high-dose statins. However, ACC/AHA guidelines can be easily adopted in Asia as there is a wealth of data available for atorvastatin in primary and secondary prevention of atherosclerotic cardiovascular disease with similar efficacy and safety profiles in the white and Asian populations.

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Cost-effectiveness of Evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease

Cost-effectiveness of Evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease

We tested various assumptions of the treatment benefit (Table 4). A 3-year time before cardiovascular mortality ben- efits emerge yielded an ICER of $245 066 and a value-based net price of $10 221 per year. A 7-year delay in the cardiovas- cular mortality treatment benefit yielded an ICER of $293 720 per QALY, and a net value-based price of $9188 per year. In the case of no lifetime cardiovascular mortality reduction, the ICER was $483 800 per QALY, and the net value-based price was $7246. This reflects the improvements in the rate of subse- quent events, health state utilities (the quality of the life- years), and cardiovascular disease events and procedures costs by reducing nonfatal events, even in the absence of direct sur- vival benefit. Additional scenarios are shown in Table 4. If all patients were receiving ezetimibe and statin therapy, then the ICER was $271 313. When only the US payer perspective was integrated into the model, then the ICER was $304 392 per QALY, and the net value-based price was $8206. At current list price, the LDL cholesterol treatment initiation threshold for pa- tients with ASCVD that would yield an ICER of $150 000 per QALY was calculated to be at least 119 mg/dL (at this thresh- old, mean LDL cholesterol level for the ASCVD population is 144 mg/dL) and at the discounted price at least 80 mg/dL (at this threshold, mean LDL cholesterol level for the ASCVD popu- lation is 110 mg/dL). The annual event rate for the ASCVD popu- lation that would yield an ICER of $150 000 per QALY was cal- culated to be 13.5 per 100 patient-years at list price and 7.1 per 100 patient-years at the discounted price.

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Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey

Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey

Inflammatory myopathies have been linked to cardio- vascular risk factors, including diabetes, hypertension, and ischemic heart disease. In a recent study, the preva- lence of hypertension and diabetes in these patients was far higher than in the general population (62% and 29% compared with 9% and 4%, respectively) [9]. Another study found that the incidence of acute MI and cerebro- vascular accident was higher in patients with dermato- myositis and polymyositis than in age- and gender- matched controls. In that study, the presence of hyper- tension and hyperlipidemia increased the risk of arterial events whereas the use of non-steroid immunomodula- tors decreased the risk [10]. Although we were not able to examine detailed risk factor profiles in individual patients in this study, it is possible that hypertension and diabetes may be appropriate targets for screening and early intervention in patients with dermatomyositis. Future studies evaluating the potential benefit of more intense glucose and blood pressure monitoring in the outpatient setting in this population would be helpful. The risk of statins in patients with inflammatory myopa- thies may complicate the treatment of hyperlipidemia; however, screening and treatment with lifestyle changes and non-statin medications may also be warranted in this population.

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Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients

Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients

Background: This study evaluated the proportion of patients with atherosclerotic cardiovascular disease (ASCVD) and probable heterozygous familial hypercholesterolemia (HeFH) achieving $50% reduction in low-density lipoprotein cholesterol (LDL-C) or reaching the LDL-C #70 mg/dL threshold, after initiating or modifying statin, and/or ezetimibe therapy. Materials and methods: Adult ASCVD patients with baseline LDL-C .70 mg/dL (index) and a subset of patients with probable HeFH (proxied by LDL-C $190 mg/dL) were identified between January 1, 2012, and August 31, 2014, from the IQVIA electronic medical record database. Patients were followed for 12 months pre-index to examine baseline lipid-lowering ther- apy (LLT) use, and 12 months post index to evaluate treatment modifications and post-treatment LDL-C levels, stratified by type of treatment received and LDL-C levels at baseline.

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Androgen therapy and atherosclerotic cardiovascular disease

Androgen therapy and atherosclerotic cardiovascular disease

However, despite the association between excess andro- gen in women and insulin resistance, CVD risk factors and angiographical evidence of atherosclerosis, there remains no evidence of increase cardiovascular mortality in these women. Additionally, in female-to-male transsexuals, testos- terone therapy has not been linked to excess cardiovascular mortality or morbidity (van Kesteren et al 1997). Therefore, the question of the cardiovascular safety of androgen therapy in women remains unanswered. Based on existing observa- tions, androgen use may increase insulin resistance in women with a consequent sequalae of cardiovascular effects however apart from the observations in women with PCOS and type 2 diabetes, and animal data suggesting androgens promote atherosclerosis in females, there is no solid data to support the claim (Figure 4). More work is necessary to establish a real link between androgens, insulin resistance and athero- sclerosis in women.

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Cardiovascular disease risk among Chinese antiretroviral naïve adults with advanced HIV disease

Cardiovascular disease risk among Chinese antiretroviral naïve adults with advanced HIV disease

on Adverse events of Anti-HIV Drugs (D:A:D) risk scores and the American College of Cardiology/American Heart Association (ACC/AHA) Atherosclerotic Cardiovascular Disease Risk Score (ASCVD) [4–8]. However, few studies have focused on CVD risk assessment among individuals with HIV in Asia. Two studies from Thailand found the prevalence of predicted cardiovascular risk in HIV- infected Thai patients was relatively low [9, 10]. In China, the prevalence of risk factors for CVD is high in the gen- eral population [11, 12], and CVD has become the leading cause of morbidity and mortality in recent decades [13]. No studies to date have assessed the underlying preva- lence of CVD risk factors among Chinese individuals with HIV prior to initiation of ART.

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The Application of the LDL Principle

The Application of the LDL Principle

The LDL Principle has recently been invoked to describe the observation that lowering the LDL cholesterol (by whatever means) results in a lowering of atherosclerotic cardiovascular events. The scientific basis of the LDL Principle dates back to the discovery that the LDL receptor is the prime determinant of the circulating LDL-c concentration. Since that time, major advances have been made at both the basic and clinical science level in our understanding of the pathogenesis and reversal of atherosclerosis. The incorporation of atherogenic lipoproteins plus inflammatory mediators into plaque formation permits the targeted intervention into preventing plaque rup- ture. In addition, genetic studies identifying individuals with unique phenotypes of either abnor- mally high or low LDL-c concentrations have provided insight into possible therapeutic modalities that have recently provided the physician with the tools necessary to apply the LDL Principle to achieve reversal of atherosclerosis. The epidemic of atherosclerotic cardiovascular disease has resulted in numerous randomized controlled intervention trials in an attempt to identify ap- proaches to reduce ASCD morbidity and mortality. Recently published data indicate that circulat- ing LDL-c levels of 50 mg/dl or less are not only physiologic at birth but also effective in greatly reducing cardiovascular disease. In addition, the recent availability of two PCSK9 inhibitors pro- vides the primary care physician with the possibility of achieving this low level of LDL-c even in statin intolerant patients. The widespread availability of the coronary artery calcium scan plus the inclusion of traditional cardiovascular risk factors in risk assessment has enabled the physician to readily identify asymptomatic individuals at high risk for cardiovascular events. Aggressively ap- plying the LDL Principle to these individuals has the potential of greatly reducing cardiovascular mortality. This review will document the scientific basis for this principle and provide the argu- ments in favor of its aggressive application.

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Chemokine receptor mutant CX3CR1 M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans

Chemokine receptor mutant CX3CR1 M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans

The chemokine receptor CX3CR1 is a proinflammatory leukocyte receptor specific for the chemokine fractalkine (FKN or CX3CL1). In two retrospective studies, CX3CR1 has been implicated in the patho- genesis of atherosclerotic cardiovascular disease (CVD) based on statistical association of a common recep- tor variant named CX3CR1-M280 with lower prevalence of atherosclerosis, coronary endothelial dys- function, and acute coronary syndromes. However, the general significance of CX3CR1-M280 and its putative mechanism of action have not previously been defined. Here we show that FKN-dependent cell- cell adhesion under conditions of physiologic shear is severely reduced in cells expressing CX3CR1-M280. This was associated with marked reduction in the kinetics of FKN binding as well as reduced FKN-induced chemotaxis of primary leukocytes from donors homozygous for CX3CR1-M280. We also show that CX3CR1- M280 is independently associated with a lower risk of CVD (adjusted odds ratio, 0.60, P = 0.008) in the Off- spring Cohort of the Framingham Heart Study, a long-term prospective study of the risks and natural his- tory of this disease. These data provide mechanism-based and consistent epidemiologic evidence that CX3CR1 may be involved in the pathogenesis of CVD in humans, possibly by supporting leukocyte entry into the coronary artery wall. Moreover, they suggest that CX3CR1-M280 is a genetic risk factor for CVD. J. Clin. Invest. 111:1241–1250 (2003). doi:10.1172/JCI200316790.

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Cardiovascular Disease among Syrian refugees: a descriptive study of patients in two Médecins Sans Frontières clinics in northern Lebanon

Cardiovascular Disease among Syrian refugees: a descriptive study of patients in two Médecins Sans Frontières clinics in northern Lebanon

ACE-I: Angiotensin Converting Enzyme Inhibitor; ARB: Angiotensin Receptor II Blocker; ASCVD: Atherosclerotic Cardiovascular Disease; BB: β -blocker; CABG: Coronary Artery Bypass Graft; CHD: Coronary Heart Disease; CI: Confidence Interval; CRF: Case Report Form; CVD: Cardiovascular Disease; DALYs: Disability Adjusted Life Years; DAZ: Dar Al Zahara; GBD: Global Burden of Disease; GP: General Practitioner; HIV/AIDS: Human Immunodeficiency Virus/Autoimmune Deficiency Syndrome; LMICs: Low- and Middle-Income Countries; LTFU: Lost to Follow Up; MOPH: Ministry of Public Health; MSF: Médecins sans Frontières; NCD: Noncommunicable Disease; NGO: Non- governmental Organisation; PHC: Primary Health Centre; PSEC: Patient Support Education and Counselling; PTCA: Percutaneous Transluminal Coronary Angioplasty; PVD: Peripheral Vascular Disease;

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Metabolic syndrome in men and women with upper  or lower types of body fat distribution

Metabolic syndrome in men and women with upper or lower types of body fat distribution

It is difficult to divide the examined patients with obe- sity into groups based on the values of waist circumfer- ence because this characteristic is very variable, and the variability is not only ethnic or population [4], but also individual as indicated by our results on the coefficients of variation for the examined obese men and women. At the same time, WHR has a significantly smaller individ- ual variability, and, most importantly, it allows us to dis- tinguish obese male and female groups with low risk of atherosclerotic cardiovascular disease and type 2 diabe- tes mellitus. It should be noted that both men and women in the groups with lower type of fat distribution were missing such a component of metabolic syndrome as hy- perglycemia i.e. they had the minimal risk of type 2 dia- betes mellitus.

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Identification of biomarkers in macrophages of atherosclerosis by microarray analysis

Identification of biomarkers in macrophages of atherosclerosis by microarray analysis

AS: Atherosclerosis; ASCVD: Atherosclerotic cardiovascular disease; BP: Biological process; CC: Cell component; CD55: Complement decay-accelerating factor; CTRP1: C1q/TNF-related proteins-1; DEG: Differentially expressed gene; DYNC2H1: Dynein cytoplasmic 2 heavy chain 1; ER: Endoplasmic reticulum; GEO: Gene Expression Omnibus; GnRH: Gonadotropin-releasing hormone; GO: Gene Ontology; IL-1: interleukin-1; IL-6: interleukin-6; IRF2BP2: Interferon regulatory factor 2-binding protein 2; KDELR3: KDEL endoplasmic reticulum protein retention receptor 3; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDL: Low-density lipoprotein; MCODE: Molecular Complex Detection; MF: Molecular function; PPI: Protein – protein interaction; STRING: Search Tool for the Retrieval of Interacting Genes; TNF- α : Tumor necrosis factor- α ; TOR: Target of rapamycin

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Prevalence of testosterone deficiency in HIV infected men under antiretroviral therapy

Prevalence of testosterone deficiency in HIV infected men under antiretroviral therapy

ACC: American college of cardiology; AHA: American heart association; AIDS: Acquired Immune Deficiency Syndrome; ASCVD: Atherosclerotic cardiovascular disease; BMI: Body mass index; cART: Combined antiretroviral therapy; CDC: Centers for Disease Control and Prevention; FI: Fusion inhibitor; FRS: Framingham risk score; FSH: Follicle stimulating hormone; FT: Free testosterone; HbA1c: Glycosylated hemoglobin; HDL: High density lipoprotein; HIV: Human immunodeficiency virus; HPG: Hypothalamic-pituitary-gonadal; IDF: International diabetes federation; II: Integrase inhibitor; LDL: Low density lipoprotein; LH: Luteinizing hormone; MS: Metabolic syndrome; NNRTI: Non- nucleoside reverse transcriptase inhibitor; NRTI: Nucleoside reverse transcriptase inhibitor; PI: Protease inhibitor; SHBG: Sex hormone binding globulin; TT: Total testosterone

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The relationship between Lp(a) and CVD outcomes: a systematic review

The relationship between Lp(a) and CVD outcomes: a systematic review

(CHD) [56], non-fatal myocardial infarction (MI) [52, 55], cardiovascular death [52, 55, 57], atherosclerotic events [53, 54], non-haemorrhagic stroke [54, 65], heart failure (HF) [58], TIA [56] and all deaths [57, 58]. Six studies used Cox proportional hazards models [54–56, 58, 61, 64], with one study reporting results from stepwise multiple logistic and Cox regression analyses [54]. and one report- ing a multiple logistic regression model [57]. Age was considered as a variable in all but one study [54], and simi- larly gender was considered in all but one study [52]. All of the studies included additional variables. These varied in type and number across the studies and studies re- ported different results for models adjusted with different groups of variables. However, only one study included LDL-C in their model [54]. This study (Cleveland Clinic Hemodialysis Cohort) [54] found that baseline Lp(a) concentration was a significant independent risk fac- tor (p = 0.001) for clinical events attributed to athero- sclerotic cardiovascular disease in patients receiving chronic haemodialysis treatment of end-stage renal disease. The only study to report the use of an iso- form independent Lp(a) assay (CHOICE [53]) simi- larly reported that high Lp(a) levels (≥52.5 nmol/L) predicted a 30 % to 40 % increased risk of elevated atherosclerotic cardiovascular disease (ASCVD) in dia- lysis patients, but that the association of ASCVD with low molecular weight LMW isoforms (increased risk of 60 % to 90 %) was stronger than the association with high Lp(a) concentration.

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Sex disparity in the management and outcomes of dyslipidemia of diabetic patients in the Arabian Gulf: findings from the CEPHEUS study

Sex disparity in the management and outcomes of dyslipidemia of diabetic patients in the Arabian Gulf: findings from the CEPHEUS study

Results: The mean age of the cohort ( n = 3336) was 57 ± 11 years and 45% ( n = 1486) were females. Females were less likely to be on rosuvastatin (7.6% vs 12%; P < 0.001), atorvastatin (41% vs 46%; P = 0.005) and combination hypolipidemic therapy (5.6% vs 2.8%; P < 0.001) but more likely to be on simvastatin (51% vs 39%; P < 0.001) than males. Females, especially those with very high atherosclerotic cardiovascular disease (ASCVD) risk status, were also less likely to achieve LDL-cholesterol [adjusted odds ratio (aOR), 0.58; 95% confidence interval (CI): 0.40 – 0.86; P = 0.006], non-HDL-cholesterol [aOR, 0.68; 95% CI: 0.46 – 0.99; P = 0.048] and apolipoprotein B [aOR, 0.64; 95% CI: 0.44 – 0.92; P = 0.016] lipid targets. Conclusions: Diabetic women were less likely to be on optimal hypolipemic therapy and consequently less likely to attain lipid goals compared to men. This shows a sex gap on dyslipidemia treatment in the region. Diabetic women with very high ASCVD risk status need to be aggressively treated to lower their risk of cardiovascular events.

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Metabolic syndrome in rheumatoid arthritis: case control study

Metabolic syndrome in rheumatoid arthritis: case control study

Morocco is one of the countries of North Africa with un- met need of sustainable healthcare delivery systems. North Africa is a region with challenging political, climatic and geographical conditions. Data from small studies in the re- gion showed that RA is frequently diagnosed late and many patients present with active disease and severe disability. Despite this, only a small proportion of patients receive DMARDs particularly biologic DMARDS, and the scarcity of medical and social resources is a barrier to appropriate treatment in many countries [9-14]. Morocco had also par- ticipated in two international studies: QUEST RA study [15], which is a successful example of quantitative clinical measuring of RA as part of routine clinical care in a large number of centers across more than 30 countries including countries from Europe (France, Germany, Netherlands....), USA, Argentina, Brazil, Morocco, and United Arab Emirates. This study has suggested high disease activity in our country. The second study is COMORA study: comorbidities in RA (data not yet published), these two studies suggest a high disease activity in our country (300 patients from 10 centers of the country), the use of high- dose of corticoids, and a more frequent association with hyeprtension pressure, dyslipidemia, overweight and less fre- quent exposure to tobacco and alcohol. Solomon A et al. [16] have assessed the risk factor profiles for atherosclerotic cardiovascular disease in black and other Africans with established rheumatoid arthritis and found that proportions of individual metabolic syndrome components differed be- tween black and other patients but their total numbers of metabolic risk factors and metabolic syndrome frequencies were similar. From these data from cross-sectional studies in Africa, we can assume that the activity profile and Sever- ity of RA in Africa is quite different from Western countries. Furthermore, metabolic syndrome and activity are intimately linked. Hence, we aimed to assess the frequency of meta- bolic syndrome and its components and evaluate the sup- posed association with disease activity and severity of RA.

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Prevalence and long-term outcomes of non-alcoholic fatty liver disease among elderly individuals from the United States

Prevalence and long-term outcomes of non-alcoholic fatty liver disease among elderly individuals from the United States

mg/g or an estimated GFR of ≤60 mL/min/1.73m 2 . The atherosclerotic cardiovascular disease (ASCVD) risk score was calculated from each participant’s age, race, sex, smok- ing status, presence of diabetes, systolic blood pressure, an- tihypertensive medication, serum cholesterol and high density lipoprotein levels [33]. NAFLD fibrosis score (NFS) [34] and aspartate aminotransferase-to-platelet ratio index (APRI) [35], serum markers of fibrosis, were calculated ac- cording to the published formulas. History of cardiovascu- lar disease (CVD) was defined by self-reported medical history of congestive heart failure, heart attack, or stroke. History of cancer was also defined by self-reported medical history of any cancer.

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Impact of metabolic syndrome on lipid target achievements in the Arabian Gulf: findings from the CEPHEUS study

Impact of metabolic syndrome on lipid target achievements in the Arabian Gulf: findings from the CEPHEUS study

abdominal obesity, elevated triglycerides, reduced HDL‑C, elevated blood pressure, and elevated blood glucose) in atherosclerotic cardiovascular disease (ASCVD) risk patients (N = 4171). As per recent unified definition by the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) using the modified National Cholesterol Educa‑ tion Program–Adult Treatment Panel III (NCEP ATP III) guidelines, MetS was defined as having three or more of the following criteria: (1) increased abdominal obesity (waist circumference of ≥94 cm for men and ≥80 cm for women for Middle Eastern (Mediterranean/ European) populations), (2) elevated triglycerides of ≥150 mg/ dL (1.7 mmol/L), (3) reduced HDL‑C of <40 mg/dL (1.04 mmol/L) for males and <50 mg/dL (1.3 mmol/L) for females, (4) elevated BP ≥130 mmHg for systolic and/or ≥85 mmHg for diastolic, and (5) elevated fasting blood glucose of ≥100 mg/dL (5.6 mmol/L). Criteria for ASCVD risk status was adapted from the National Lipid Associa‑ tion criteria for atherosclerotic cardiovascular disease. High risk group included patients with ≥3 major ASCVD risk factors, diabetes mellitus (type 1 or 2) with 0/1 major ASCVD risk factor and LDL‑C ≥190 mg/ dL (5.02 mmol/L) (severe hypercholesterolemia). Very high risk group included ASCVD (CHD, PAD, CVD), diabetes mellitus with ≥2 other major ASCVD risk factors

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The importance of proteinuria and prior cardiovascular disease in all major clinical outcomes of atherosclerotic renovascular disease – a single-center observational study

The importance of proteinuria and prior cardiovascular disease in all major clinical outcomes of atherosclerotic renovascular disease – a single-center observational study

The clinical significance of renal vascular anatomy is un- clear. Several studies, including publications from this same dataset, demonstrated that severity of stenosis correlates inversely with long-term patient survival [15, 26, 30], but has no bearing on degree of renal dysfunction at presenta- tion and renal functional outcome. This is dependent on the degree of parenchymal disease, which is related to the actual ‘haemodynamic significance’ of a stenosis rather than its ‘severity’ on cross-sectional imaging studies [26, 28, 33]. In addition, patients with severe stenosis invariably have widespread systemic atherosclerosis and significant cardio- vascular comborbidities, hence most die before progressing to ESKD. Our results point towards a trend between higher patency score and better long-term clinical outcomes, suggesting that in this complex, heterogenous condition, outcomes are influenced by both parenchymal damage and the ‘haemodynamic significance’ of stenosis. However, the patency score used in this analysis does not distinguish between unilateral severe stenosis and bilateral less haemo- dynamically significant disease, hence results probably reflect the effect of overall atherosclerotic burden rather than specific haemodynamic compromise.

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<p>Renal Artery Stenosis in the Patient with Hypertension: Prevalence, Impact and Management</p>

<p>Renal Artery Stenosis in the Patient with Hypertension: Prevalence, Impact and Management</p>

Abstract: Atherosclerosis is the primary cause of renal artery stenosis. Atherosclerotic renal artery stenosis (ARAS) is associated with three clinical problems: renovascular hypertension, ischemic nephropathy and cardiac destabilization syndrome which pose huge healthcare impli- cations. There is a signi fi cant rate of natural disease progression with worsening severity of renal artery stenosis when renal revascularization is not pursued in a timely manner. Selective sub- groups of individuals with ARAS have had good outcomes after percutaneous renal artery stenting (PTRAS). For example, individuals that underwent PTRAS and had improved renal function were reported to have a 45% survival advantage compared to those without improve- ment in their renal function. Advances in the imaging tools have allowed for better anatomic and physiologic measurements of ARAS. Measuring translesional hemodynamic gradients has allowed for accurate assessment of ARAS severity. Renal revascularization with PTRAS provides a survival advantage in individuals with signi fi cant hemodynamic renal artery stenosis lesions. It is important that we screen, diagnosis, intervene with invasive and medical treatments appropriately in these high-risk patients.

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Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population

Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population

were older than current smokers or nonsmokers, and fibrino- gen levels were not statistically different according to smok- ing status after adjusting for age. Not only current smoking but also past smoking can interact with fibrinogen and con- tribute to the development of carotid atherosclerosis, because atherosclerosis is a chronic progressive condition. However, we could not observe an association between fibrinogen and atherosclerosis among former smokers. The former smok- ers in our study were not entirely homogeneous, as some of them might have smoked cigarettes for a long period and only recently quit, while others may not have smoked for a long time. It has been reported that cardiovascular risk gradually decreases after smoking cessation and that fibrinogen and other metabolic risk profiles among quitters differ by the length of non-smoking period. 36-38 Notwithstanding, we were

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