Discontinuing low-dose acetylsalicylic acid after gastrointestinal bleeding is associated with increased mortality.

BACKGROUND: Gastrointestinal bleeding is a common clinical problem in patients using low-dose acetylsalicylic acid (ASA). It is uncertain whether aspirin should continue to be used in patients who develop acute gastrointestinal bleeding during low-dose ASA therapy. AIMS: To assess whether ASA should be continued in patients who develop GI bleeding during low-dose ASA. METHODS: All patients admitted to an academic hospital for acute gastrointestinal bleeding between 2009 and 2011 were reviewed retrospectively. Clinical characteristics, comorbidities, medications and treatments were recorded from the patient records. Patients were divided into two groups based on continuing or discontinuing ASA after discharge. RESULTS: A total of 548 patients were included. ASA was continued in 282 (51.5%) (ASAc group) and discontinued in 266 (48.5%) patients (ASAd group). ASAc patients had more often coronary artery disease (57.8% vs. 42.5%, p < .001) and peripheral artery disease (17.4% vs. 9.0%, p = .004) than ASAd patients, whereas no differences were found in other comorbidities. There was no difference in 30-day all-cause mortality between ASAd and ASAc groups. However, after adjustment for age, gender and comorbidities, one-year all-cause mortality was double in the ASAd group (hazard ratio 2.16, 95% confidence interval 1.39-3.35). ASAd and ASAc groups did not differ with respect to cardiovascular mortality (4.9% vs. 5.3%, p = .811, respectively) or re-bleeding (10.2% vs. 9.2%, p = .713, respectively). CONCLUSION: Continuing low-dose ASA after gastrointestinal bleeding was associated with lower all-cause mortality during the first year without increasing the risk of re-bleeding.

Medical certificate education: controlled study between lectures and flipped classroom.

BACKGROUND: Finnish permanent residents are covered by social security insurance administered by the Social Insurance Institution of Finland. The procedure of insurance is initiated with medical certificate written by the treating doctor. Thus, the doctor must have certificate writing skills accompanied with the knowledge of the content and goals for insurance. Quality certificates are important part of doctors' professional skills worldwide and most effective teaching methods for learning these should be investigated. METHODS: Medical certificate data were collected from two independent courses of fourth-year student taught in autumn 2015 (N = 141) and 2016 (N = 142) in the medical faculty of the University of Eastern Finland. A random sample of 40 students per course was drawn for the analysis. All certificates were analyzed as one sample. This was done to obtain reliable results with internal control group on the differences between two teaching methods, the traditional approach and the flipped classroom (FC) approach, in 2015 and 2016, respectively. The medical certificates were evaluated and scored with a rubric (range: - 4.00-14.25) by two independent experienced specialists. RESULTS: Compared to students in the traditional classroom, students involved in the FC received significantly higher scores in all relevant sections of the assessed certificates. The mean of the total scores was 8.87 (SD = 1.70) for the traditional group and 10.97 (SD = 1.25) for the FC group. Based on the common language effect size, a randomly selected student from the FC group had an 85% probability of receiving a higher total score than a student from the traditional group. CONCLUSION: In this study, the FC approach resulted in a statistical significant improvement in the content and technical quality of the certificates. The results suggest that the FC approach can be applied in the teaching of medical certificate writing.

ACE inhibitors and the risk of acute pancreatitis-a population-based case-control study.

PURPOSE: The aim of this study was to examine the association between angiotensin converting enzyme (ACE) inhibitor use and the risk of acute pancreatitis. METHODS: Information on all 4966 cases hospitalized in 2008-2010 for acute pancreatitis was retrieved from the Finnish national registers on hospital discharges and prescriptions. A total of 24 788 age and sex-matched population-based controls were randomly selected using density sampling. ACE inhibitor use between 1 January 2003 and the index date were determined by the date of hospitalization for acute pancreatitis among the cases. The incidence rate ratios of acute pancreatitis not diagnosed as biliary or alcohol-induced were modeled by conditional logistic regression and adjusted for comorbidities. RESULTS: A total of 1276 (26%) cases and 3946 (16%) controls had been exposed to ACE inhibitors. The use of ACE inhibitors was associated with an increased incidence rate of acute pancreatitis (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.59-1.95). The increase was slightly higher among current new users (OR 1.86, 95%CI 1.65-2.09) and somewhat lower among current prevalent (OR 1.54, 95%CI 1.35-1.75) and former users (OR 1.51, 95%CI 1.31-1.74). CONCLUSIONS: Angiotensin converting enzyme inhibitor use seems to be associated with a moderately increased risk of acute pancreatitis. Copyright © 2017 John Wiley & Sons, Ltd.

Use of statins and the risk of acute pancreatitis: a population-based case-control study.

PURPOSE: The aim of this research was to examine the association between statin use and the risk of acute pancreatitis. METHODS: This register-based case-control study with incidence density sampling was based on 4376 patients hospitalized in 2008-2010 for acute pancreatitis and 19 859 randomly selected age and sex-matched controls from the adult population of Finland. The relationship between statin use from 1 January 2004 to the index date and the relative incidence rate of acute pancreatitis was modelled by conditional logistic regression. The rate ratios were adjusted for comorbidities. RESULTS: A total of 826 (19%) cases and 2589 (13%) controls had been exposed to statins. Statin use was associated with an increased incidence rate of acute pancreatitis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.13-1.39). This increase was seen especially during the first year of use both among current (OR 1.37, 95% CI 0.94-2.00 for at most 3 months of use and OR 1.32, 95% CI 1.07-1.63 for 4-12 months of use) and former users (OR 1.64, 95% CI 1.33-2.03). The overall association remained when restricting analyses to participants with current use only, or with no history of gallstone or alcohol-related diseases, or with no comorbidities or medicines other than statins. CONCLUSIONS: Statin use seems to be associated with an increased risk of acute pancreatitis. The association is more apparent during the first year of statin use and among former users.

Effect of statin use on outcome of symptomatic cholelithiasis: a case-control study.

BACKGROUND: Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment. METHODS: A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups. RESULTS: Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins. CONCLUSIONS: Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.

Topical anti-inflammatory agents for seborrhoeic dermatitis of the face or scalp.

BACKGROUND: Seborrhoeic dermatitis is a chronic inflammatory skin disorder affecting primarily the skin of the scalp, face, chest, and intertriginous areas, causing scaling and redness of the skin. Current treatment options include antifungal, anti-inflammatory, and keratolytic agents, as well as phototherapy. OBJECTIVES: To assess the effects of topical pharmacological interventions with established anti-inflammatory action for seborrhoeic dermatitis occurring in adolescents and adults. SEARCH METHODS: We searched the following databases up to September 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 9), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We searched five trials databases and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs in adults or adolescents (> 16 years) with diagnosed seborrhoeic dermatitis of the scalp or face, comparing topical anti-inflammatory treatments (steroids, calcineurin inhibitors, and lithium salts) with other treatments. DATA COLLECTION AND ANALYSIS: Pairs of authors independently assessed eligibility for inclusion, extracted data, and evaluated the risk of bias. We performed meta-analyses if feasible. MAIN RESULTS: We included 36 RCTs (2706 participants), of which 31 examined topical steroids; seven, calcineurin inhibitors; and three, lithium salts. The comparative interventions included placebo, azoles, calcipotriol, a non-steroidal anti-inflammatory compound, and zinc, as well as different anti-inflammatory treatments compared against each other. Our outcomes of interest were total clearance of symptoms, erythema, scaling or pruritus scores, and adverse effects. The risk of bias in studies was most frequently classified as unclear, due to unclear reporting of methods.Steroid treatment resulted in total clearance more often than placebo in short-term trials (four weeks or less) (relative risk (RR) 3.76, 95% confidence interval (CI) 1.22 to 11.56, three RCTs, 313 participants) and in one long-term trial (lasting 12 weeks). Steroids were also more effective in reducing erythema, scaling, and pruritus. Adverse effects were similar in both groups.There may be no difference between steroids and calcineurin inhibitors in total clearance in the short-term (RR 1.08, 95% 0.88 to 1.32, two RCTs, 60 participants, low-quality evidence). Steroids and calcineurin inhibitors were found comparable in all other assessed efficacy outcomes as well (five RCTs, 237 participants). Adverse events were less common in the steroid group compared with the calcineurin group in the short-term (RR 0.22, 95% CI 0.05 to 0.89, two RCTs, 60 participants).There were comparable rates of total clearance in the steroid and azole groups (RR 1.11, 95% CI 0.94 to 1.32, eight RCTs, 464 participants, moderate-quality evidence) as well as of adverse effects in the short-term, but less erythema or scaling with steroids.We found mild (class I and II) and strong (class III and IV) steroids comparable in the assessed outcomes, including adverse events. The only exception was total clearance in long-term use, which occurred more often with a mild steroid (RR 0.79, 95% CI 0.63 to 0.98, one RCT, 117 participants, low-quality evidence).In one study, calcineurin inhibitor was more effective than placebo in reducing erythema and scaling, but there were similar rates in total clearance or adverse events for short-term treatment. In another study, calcineurin inhibitor was comparable with azole when erythema, scaling, or adverse effects were measured for longer-term treatment.Lithium was more effective than placebo with regard to total clearance (RR 8.59, 95% CI 2.08 to 35.52, one RCT, 129 participants) with a comparable safety profile. Compared with azole, lithium resulted in total clearance more often (RR 1.79, 95% CI 1.10 to 2.90 in short-term treatment, one RCT, 288 participants, low-quality evidence). AUTHORS' CONCLUSIONS: Topical steroids are an effective treatment for seborrhoeic dermatitis of the face and scalp in adolescents and adults, with no differences between mild and strong steroids in the short-term. There is some evidence of the benefit of topical calcineurin inhibitor or lithium salt treatment. Treatment with azoles seems as effective as steroids concerning short-term total clearance, but in other outcomes, strong steroids were more effective. Calcineurin inhibitor and azole treatment appeared comparable. Lithium salts were more effective than azoles in producing total clearance.Steroids are similarly effective to calcineurin inhibitors but with less adverse effects.Most of the included studies were small and short, lasting four weeks or less. Future trials should be appropriately blinded; include more than 200 to 300 participants; and compare steroids to calcineurin inhibitors or lithium salts, and calcineurin inhibitors to azoles or lithium salts. The follow-up time should be at least one year, and quality of life should be addressed. There is also a need for the development of well-validated outcome measures.

Patient perspective in health technology assessment of pharmaceuticals in Finland.

OBJECTIVES: The need to consider the patient perspective in health technology assessments (HTA) has been widely recognized. In July 2012, the Finnish Medicines Agency (Fimea) published a national recommendation for integrating the patient perspective into the HTAs of pharmaceuticals. The aim of this study is to describe the development of the recommendation for integrating the patient perspective into the HTA process of pharmaceuticals in Finland. METHODS: The development of the recommendation was based on a review of international recommendations and experiences of patient and public involvement in HTA. The draft recommendation was tested in two focus group discussions (n = 7 patients) and three individual interviews among diabetes patients (type 1 or 2) using long-acting insulin treatment. The recommendation was open for public consultation in April 2012 and revised according to the comments received. RESULTS: Patients will be involved in multiple stages of Fimea's HTA process. The recommendation includes step-by-step instructions on how to assess the patient perspective. The main focus is on qualitative interviews, which will be conducted at the beginning of the assessments to gain information, particularly on patient preferences and values, including positive and negative outcomes important to patients and ethical and social aspects of the medicine's use. CONCLUSIONS: The recommendation will act as a tool to integrate patients' experiences, needs and preferences into Fimea's HTAs of pharmaceuticals.

[Focusing on the patient perspective in the use of medicines]. / Potilas päättää lääkkeen otosta.

Patients' own views on medicines will grow in importance when trying to improve the quality of medicines use. Today, there is a general trend from paternalism towards concordance. Clarifying the patient's expectations and fears/worries is the first step in establishing a patient centered approach. A reserved attitude towards medicines is common, and therefore two-way communication is essential in ensuring a rational use of medicines. Patients use several information sources, which may cause unnecessary worries and discontinuation of treatment. Improving physicians' communication skills and use of techniques like motivational interviewing may be helpful in managing the situation.

Comparison of the MDRD Study and the CKD-EPI Study equations in evaluating trends of estimated kidney function at population level: findings from the National FINRISK Study.

BACKGROUND: There are no data comparing the Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Study equations in the evaluation of time-dependent trend of estimated glomerular filtration rate (eGFR) in the general population. METHODS: Changes in eGFR and in the association of eGFR with kidney disease and cardiovascular disease (CVD) risk factors across age groups were estimated in two independent cross-sectional population surveys in Finland in 2002 and 2007 with 11 277 study participants, aged 25-74 years, using both the MDRD and the CKD-EPI equations. RESULTS: A trend towards decreasing eGFRs between the study years was observed using both equations, but the trend was more substantial when using the MDRD equation. The MDRD equation yielded lower estimates of eGFR than the CKD-EPI equation, with small mean difference between the equations at low eGFR level but substantial at the level of only mildly decreased or near-normal to normal kidney function. Decrease of eGFR was associated with an increase in CKD and CVD risk factors. However, an increase of risk factors was not observed among those who had mildly decreased eGFR by only the MDRD equation but not by the CKD-EPI equation. CONCLUSION: In comparison with the CKD-EPI equation, the MDRD equation augmented the trend of increasing prevalence of CKD, showed a weaker association with risk factors and tended to assign impaired renal function to individuals without an excess of cardiovascular risk factors.

Trends in estimated kidney function: the FINRISK surveys.

We evaluated the temporary trend in estimated glomerular filtration rate (eGFR) of subjects aged from 25 to 74 years between two cross-sectional population surveys in 2002 and in 2007. The mean eGFR across age-groups, the prevalences of eGFR categories, and the prevalence of chronic kidney disease (CKD) stage 3­5 defined by eGFR\60 mL/min/1.73 m2 were defined in sex- and age-specific groups using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Study equation. The eGFR decreased from year 2002 to 2007 across the age-groups in both genders. The prevalence of CKD stage 3­5 (eGFR\60 mL/min/1.73) increased in women from 1.8 to 3.1% (P=0.017), but not in men. In the combined analysis of both genders, CKD stage 3­5 was markedly more common in 2007 compared to 2002, with odds ratio (OR) 1.59 (95% confidence interval (CI) 1.22­2.08) remaining significant after adjusting the model for age, gender, study area, hypertension, obesity, prior cardiovascular disease, and diabetes mellitus, and being at lowest when only age, gender and waist circumference were included in the model (OR 1.34; 95% CI 1.02­1.76). To conclude, the mean eGFR decreased significantly during 2002­2007 in both sexes, and CKD stage 3­5 increased in women. This trend was concurrent with increases in mean waist circumference and in the prevalence of diabetes mellitus.

Glomerular filtration rate is related to carotid intima-media thickness in middle-aged adults.

BACKGROUND: Severe renal dysfunction is associated with increased cardiovascular risk. The aim of this study was to investigate the association between renal function and carotid intima-media thickness (cIMT) in a middle-aged population-based cohort. METHODS: A total of 247 males and 258 females aged 40-62 years participated in this cross-sectional study. Renal function was assessed with estimated glomerular filtration rate (eGFR) and carotid atherosclerosis with ultrasonography as the mean IMT of the far carotid wall. RESULTS: The mean eGFR values were 90.2 (SD 16.8) ml/min/1.73 m(2) for men and 78.0 (SD 14.0) ml/min/1.73 m(2) for women, and the mean cIMT values were 0.92 (SD 0.21) mm for men and 0.82 (SD 0.12) mm for women. The mean cIMT was highest in the tertile with the lowest eGFR in both sexes (P = 0.013 for males and P = 0.031 for females). In males, the eGFR tertile was significantly associated with cIMT (P = 0.026) in a model adjusted for traditional risk factors. Renal function was also significantly associated with cIMT in a subset of 149 postmenopausal women (P = 0.008). CONCLUSIONS: Even a minor deterioration in renal function was independently associated with increased cIMT in the middle-aged male population and in the postmenopausal women. This finding underlines the importance of early detection of subjects with mildly decreased kidney function and the aggressive management of atherosclerotic risk factors in this population.

Low-density lipoprotein clearance in patients with chronic renal failure.

BACKGROUND: Chronic renal failure increases the risk of atherosclerosis. The clearance of low-density lipoprotein (LDL), a major risk factor for atherosclerosis, has been reported as being disturbed in dialysis patients. We studied LDL metabolism in non-dialyzed patients with chronic kidney disease (CKD). METHODS: LDL clearance was studied with a radiotracer method in 57 CKD patients and 10 healthy controls. RESULTS: In the CKD patients, the fractional catabolic rate of LDL apo B (LDL FCR), an indicator of LDL clearance from plasma, ranged from 0.13 to 0.56 pools/day with a mean value of 0.34 pools/day being comparable to that of the control subjects. In the renal patients, LDL FCR correlated significantly with estimated glomerular filtration rate (eGFR) (r = 0.340, P = 0.010) and this association remained significant after the adjustment with age, body mass index, gender, presence of diabetes and LDL cholesterol concentration (P = 0.004). In CKD patients with eGFR <15 mL/min/1.73 m(2) the mean LDL FCR was significantly reduced when compared to that of CKD patients with eGFR >30 mL/min/1.73 m(2) (P = 0.005). LDL apo B production rate was not associated with renal function or different between renal patients and control subjects. CONCLUSIONS: The clearance of LDL seems to be related to the severity of renal impairment, but a remarkable reduction in LDL catabolism can be observed only in patients with advanced renal failure.

Statins do not Increase the Rate of Bleeding Among Warfarin Users.

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Natural history of bleeding and characteristics of early bleeders among warfarin initiators - a cohort study in Finland.

AIMS: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. PATIENTS AND METHODS: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012). We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. RESULTS: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%-2.7%), with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%-7.1%). In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9-17.1; during 180 days-7 years before initiation, HR =1.48, 95% CI 1.15-1.90), male sex (HR =1.32, 95% CI 1.10-1.57), older age (HR =1.13, 95% CI 1.04-1.22, per 10-year increase), venous thrombosis (HR =1.83, 95% CI 1.44-2.34), pulmonary embolism (HR =1.46, 95% CI 1.11-1.91), alcohol abuse (HR =1.59, 95% CI 1.08-2.35), rheumatic disease (HR =1.40, 95% CI 1.07-1.83), and exposure to drugs with dynamic interaction mechanism with warfarin (HR =1.43, 95% CI 1.20-1.71). In age-adjusted models, Charlson comorbidity index and number of drugs predicted a graded increase in the hazard of early bleeding. CONCLUSION: The rate of hospitalizations for bleeding peaked in the beginning of warfarin therapy. Early bleeders were characterized by venous thrombosis, pulmonary embolism, and factors that increase bleeding risk without affecting the international normalized ratio.

Topical anti-inflammatory agents for seborrheic dermatitis of the face or scalp: summary of a Cochrane Review.

CLINICAL QUESTION: Are there differences in effectiveness between topical anti-inflammatory treatments (steroids, calcineurin inhibitors, or lithium salts) and placebo or azoles in the treatment of seborrheic dermatitis of the face and scalp in adults? BOTTOM LINE: The topical anti-inflammatory treatments were more effective in achieving total clearance of symptoms than placebo by 1.4-fold to 8.5-fold, but there are no considerable differences in the anti-inflammatory topical treatments or in comparison with azoles for short-term treatment. There is no evidence of treatment effects in long-term, continuous, or intermittent use of these compounds despite the chronic nature of the disease.

Statin use in patients with acute pancreatitis and symptomatic gallstone disease.

OBJECTIVE: The long-term use of statins may be associated with a decreased risk for gallstones and biliary-induced acute pancreatitis (AP). Our aim was to study the relationship of statin use and outcome of AP. METHODS: We investigated the records of 461 consecutive patients with AP and 1140 patients with symptomatic gallstones during 2008 to 2010. The use of lipid-lowering drugs, patient's characteristics, and outcome of patients were recorded. All known risk factors for AP and particularly statin use in idiopathic AP were analyzed. RESULTS: Statin use was comparable between the patients with AP (22%) and patients with cholelithiasis (24%). The frequencies of surgical treatment, duration of hospital stay, or mortality were not different between the statin users compared with the nonusers. Idiopathic AP was more often associated with the use of statins than alcohol- or gallstone-induced AP (44% vs 30% vs 13%, P < 0.002). The etiology of AP was alcohol in 56% of the patients, gallstones in 28% of the patients, and unknown (idiopathic) or miscellaneous in 16% of the patients. CONCLUSIONS: No beneficial effect of statins was observed in mortality or other outcome parameters of patients with AP. Statin use was more frequent in patients with idiopathic AP than in patients with biliary- or alcohol-induced AP.

Carbamyl adducts on low-density lipoprotein induce IgG response in LDLR-/- mice and bind plasma autoantibodies in humans under enhanced carbamylation.

AIMS: Post-translational modification of proteins via carbamylation predicts increased risk for coronary artery disease. Uremia and smoke exposure are known to increase carbamylation. The aim was to investigate the role of carbamylated low-density lipoprotein (LDL) immunization on antibody formation and atherogenesis in LDL receptor-deficient (LDLR-/-) mice, and to study autoantibodies to carbamylated proteins in humans with carbamylative load. RESULTS: LDLR-/- mice immunized with carbamylated mouse LDL (msLDL; n=10) without adjuvant showed specific immunoglobulin G (IgG) antibody levels to carbamyl-LDL and malondialdehyde-modified LDL (MDA-LDL) but not to oxidized LDL or native LDL. Immunization did not influence the atherosclerotic plaque area compared with control LDLR-/- mice immunized with native msLDL (n=10) or phosphate-buffered saline (n=11). Humans with high plasma urea levels, as well as smokers, had increased IgG autoantibody levels to carbamyl-modified proteins compared to the subjects with normal plasma urea levels, or to nonsmokers. INNOVATION: Carbamyl-LDL induced specific IgG antibody response cross-reactive with MDA-LDL in mice. IgG antibodies to carbamyl-LDL were also found in human plasma and related to conditions known to have increased carbamylation, such as uremia and smoking. Plasma antibodies to carbamylated proteins may serve as new indicator of in vivo carbamylation. CONCLUSION: These data give insight into mechanisms of in vivo humoral recognition of post-translationally modified structures. Humoral IgG immune response to carbamylated proteins is suggested to play a role in conditions leading to enhanced carbamylation, such as uremia and smoking.