Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis.

BACKGROUND: Lipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention. OBJECTIVES: This study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations. METHODS: This study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells. RESULTS: Overall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL. CONCLUSIONS: In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis.

Metabolic factors affecting hepatocellular carcinoma in steatohepatitis.

BACKGROUND & AIMS: With the rising prevalence of alcoholism, obesity and metabolic syndrome, steatohepatitis will become the leading cause of end-stage liver disease and hepatocellular carcinoma in the United States by 2025. Patients with non-alcoholic steatohepatitis and alcoholic liver disease have similar clinical and histopathological presentations, whether these similarities persist in non-alcoholic steatohepatitis and alcoholic liver disease patients with hepatocellular carcinoma remains unknown. METHODS: A retrospective analysis of the clinical features of adult patients from a large transplant center who underwent liver transplantation for steatohepatitis due to non-alcoholic steatohepatitis and alcoholic causes (alcoholic liver disease) between 1/1/02 and 1/1/12 was performed. Clinical features, explant histopathology, and clinical outcomes were compared. RESULTS: Hepatocellular carcinoma was present in 80 of 317 patients, who underwent liver transplantation for steatohepatitis with equivalent distribution in non-alcoholic steatohepatitis and alcoholic liver disease patients (24% vs 26%; P = 0.8). On multivariate analysis, significant predictors of hepatocellular carcinoma included age, ethnicity (Hispanic), and diabetes, but not BMI, hypertension or smoking. A lower risk of hepatocellular carcinoma was associated with a clinical history of hyperlipidemia. Clinical parameters were similar between patients with alcoholic liver disease - hepatocellular carcinoma and non-alcoholic steatohepatitis-hepatocellular carcinoma, except sex and presence of metabolic syndrome. non-alcoholic steatohepatitis-hepatocellular carcinoma livers retained histopathological features of non-alcoholic steatohepatitis such as ballooning and Mallory bodies, while alcoholic liver disease-hepatocellular carcinoma livers did not. There were no significant differences in hepatocellular carcinoma recurrence rates or post-transplant overall survival. CONCLUSIONS: We report the largest single-center study evaluating clinical, histopathological and outcome measures of patients undergoing liver transplantation for steatohepatitis. Older patients, diabetics, and Hispanics may warrant more frequent cancer screening due to increased risk of hepatocellular carcinoma.

Hypolipidemic and Hepatoprotective Effects of a Polyprenol-Containing Drug in Patients with Acute Coronary Syndrome.

In a double-blind placebo-controlled trial POLYNCOR (registration No. NCT03122340 at clinicaltrials.gov ), lipid-lowering and hepatoprotective effects of polyprenol-containing drug Ropren were evaluated in patients with acute coronary syndrome. After 2-months therapy, total cholesterol and ALT in the patients receiving Ropren were significantly (p<0.05) lower than in the control group. The number of patients who needed to discontinue or reduce the dose of atorvastatin due to an increase in the level of transaminases in the main group was significantly (p<0.05) lower than in the control group: 0 (0%) vs. 5 (33.3%). The more pronounced decrease in cholesterol level and hepatoprotective effect of Ropren allowed recommending this preparation to patients with acute coronary syndrome in addition to standard therapy.

Long-Term Effects of Unprovoked Venous Thromboembolism on Mortality and Major Cardiovascular Events.

BACKGROUND: Patients with unprovoked venous thromboembolism (VTE) are at an increased risk of mortality, but whether their cardiovascular risks also increase remains to be determined. We aimed to investigate the factors associated with overall mortality and major adverse cardiovascular events in patients with unprovoked VTE. METHODS AND RESULTS: We identified 2154 patients newly diagnosed with unprovoked VTE from Taiwan's National Health Insurance Database between 2000 and 2013, excluding those with reversible etiologies, underlying cancer, or autoimmune diseases. These patients with VTE were compared with an age-, sex-, and cardiovascular risk-matched cohort of 4308 controls. The risk of mortality and major adverse cardiovascular events in patients with VTE was 2.23 (CI, 1.93-2.57; P<0.0001) and 1.86 (CI, 1.65-2.09; P<0.0001) times, respectively, higher than that of the conditions in controls. These events mostly occurred during the first year after the diagnosis of unprovoked VTE. Among patients with VTE, advanced age, male sex, and comorbid diabetes mellitus indicated a higher incidence of mortality and major adverse cardiovascular events. Conversely, comorbid hyperlipidemia attenuated these risks. CONCLUSIONS: This nation-wide cohort study revealed that patients with unprovoked VTE, particularly older males with diabetes mellitus, had an elevated risk of both mortality and cardiovascular events. Risk of mortality and major adverse cardiovascular events were highest within the first year after diagnosis and persisted during the 10 years of follow-up.

Statin use and all-cause and cancer mortality: BioBank Japan cohort.

BACKGROUND: Statins are the first-line agents used to treat patients with high serum low-density lipoprotein cholesterol levels, thus reducing the risk of death from arterial sclerotic cardiovascular disease; however, little is known about the effects of non-statin pharmacological interventions on mortality as well as about the potential protective effects of statin use against cancer death. This work aimed to compare all-cause and cancer mortality among patients with hyperlipidaemia who did and did not receive statin treatment. METHODS: Between 2003 and 2007 fiscal years, we recruited Japanese patients diagnosed with hyperlipidaemia from 66 hospitals. Patients in our cohort were followed up for a maximum of 12 years to observe the causes of death. Kaplan-Meier estimates from the baseline were used to compare the mortality of patients based on the administered medicine. All-cause mortality were compared among patients with/without administration of statins and other agents; any-organ and colorectal cancer mortality were compared between patients with/without administration of statins. RESULTS: Our cohort included 41,930 patients with mean ages of 64-66 years and mean body mass indices of 24-25 kg/m2. Patients who received statin monotherapy and were treated with lifestyle modification exhibited nearly identical survival curves, whereas statin use represented a non-significant but potentially protective effect against colorectal cancer-related mortality. The lowest mortality in this cohort was associated with resin monotherapy. CONCLUSIONS: Mortality rate has been similar for patients treated with statin monotherapy and lifestyle modification. Statin monotherapy could potentially reduce any-organ- and colorectal cancer-related mortality.

Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis.

AIM: To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis (HLAP). METHODS: A total of 863 patients were admitted to our hospital for acute pancreatitis (AP) from January 2013 to March 2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During follow-up, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test. RESULTS: No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP (50.0% and 77.8%, respectively) than non-smokers (9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23 (26.1%) patients. Multivariate analysis identified current smoking (HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers (23 mo vs 42 mo), but no significant difference was documented between ex-smokers (34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers. CONCLUSION: Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.

Myocardial Structural and Biological Anomalies Induced by High Fat Diet in Psammomys obesus Gerbils.

BACKGROUND: Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils. METHODS: Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls) or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels) were evaluated. Myocardial samples were collected for pathobiological evaluation. RESULTS: Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL)-1ß and tumor necrosis factor (TNF)-α], intercellular (ICAM1) and vascular adhesion molecules (VCAM1) increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6), was downregulated. Myocardial expressions of sarco(endo)plasmic calcium-ATPase (SERCA2) and voltage-dependent calcium channel (Cacna1c) decreased, while protein kinase A (PKA) and calcium-calmodulin-dependent protein kinase (CaMK2D) expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1) did not change. CONCLUSIONS: We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.

Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH Registry.

BACKGROUND: Patients with atrial fibrillation (AF) are at increased risk of thromboembolic events. The long-term prognostic implications of AF in patients with atherothrombosis are unknown. METHODS: We compared 4-year CV outcomes in patients with and without a history of AF recorded at their baseline visit in the REACH Registry, an international, prospective cohort of patients with established atherosclerotic arterial disease (CAD, CVD, PAD) or at least 3 risk factors (RFO). RESULTS: AF status and 4 year follow-up data were available on 44,518 patients. The prevalence of AF at baseline was 10.3% (n=4582). Overall, patients with AF had approximately a 2-fold increase in the composite of CV death, MI, or stroke compared with patients without AF after adjustment for age, gender, prior ischemic event, vascular disease, congestive heart failure, diabetes, smoking, body mass index, region, aspirin and statin use (18.9% vs. 9.4%, p<0.0001). This increased risk was observed both in patients with established atherothrombosis (CAD: 15.5% vs. 8.0%, p=0.0001; CVD: 23.6% vs. 13.6%, p<0.0001; PAD: 24.3% vs. 13.5%, p=0.089) and those with multiple risk factors (RFO: 12.1% vs. 5.9%, p=0.017). Only 52% of patients with a history of AF at baseline were receiving anticoagulation at 4 years. CONCLUSIONS: Patients with a history of both AF and atherothrombosis have particularly high long-term CV risk. Despite this increased risk, almost half of all patients with AF do not receive guideline recommended anticoagulation, highlighting an important public health priority.

Factors influencing the decline in stroke mortality: a statement from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: Stroke mortality has been declining since the early 20th century. The reasons for this are not completely understood, although the decline is welcome. As a result of recent striking and more accelerated decreases in stroke mortality, stroke has fallen from the third to the fourth leading cause of death in the United States. This has prompted a detailed assessment of the factors associated with the change in stroke risk and mortality. This statement considers the evidence for factors that have contributed to the decline and how they can be used in the design of future interventions for this major public health burden. METHODS: Writing group members were nominated by the committee chair and co-chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiological studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize evidence and to indicate gaps in current knowledge. All members of the writing group had the opportunity to comment on this document and approved the final version. The document underwent extensive American Heart Association internal peer review, Stroke Council leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. RESULTS: The decline in stroke mortality over the past decades represents a major improvement in population health and is observed for both sexes and for all racial/ethnic and age groups. In addition to the overall impact on fewer lives lost to stroke, the major decline in stroke mortality seen among people <65 years of age represents a reduction in years of potential life lost. The decline in mortality results from reduced incidence of stroke and lower case-fatality rates. These significant improvements in stroke outcomes are concurrent with cardiovascular risk factor control interventions. Although it is difficult to calculate specific attributable risk estimates, efforts in hypertension control initiated in the 1970s appear to have had the most substantial influence on the accelerated decline in stroke mortality. Although implemented later, diabetes mellitus and dyslipidemia control and smoking cessation programs, particularly in combination with treatment of hypertension, also appear to have contributed to the decline in stroke mortality. The potential effects of telemedicine and stroke systems of care appear to be strong but have not been in place long enough to indicate their influence on the decline. Other factors had probable effects, but additional studies are needed to determine their contributions. CONCLUSIONS: The decline in stroke mortality is real and represents a major public health and clinical medicine success story. The repositioning of stroke from third to fourth leading cause of death is the result of true mortality decline and not an increase in mortality from chronic lung disease, which is now the third leading cause of death in the United States. There is strong evidence that the decline can be attributed to a combination of interventions and programs based on scientific findings and implemented with the purpose of reducing stroke risks, the most likely being improved control of hypertension. Thus, research studies and the application of their findings in developing intervention programs have improved the health of the population. The continued application of aggressive evidence-based public health programs and clinical interventions is expected to result in further declines in stroke mortality.

Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with pancreatic cancer: better prognosis with statin use in diabetic patients.

OBJECTIVES: The aim of this study was to clarify the impact of diabetes mellitus (DM) as well as antidiabetic, antihypertensive, and antihyperlipidemic medications such as metformin and statins on survival in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: We retrospectively reviewed the medical records of 250 patients with advanced pancreatic cancer receiving chemotherapy. Multivariate analyses of prognostic factors for survival were performed both in overall population and in subgroups with and without DM. RESULTS: Diabetes mellitus was diagnosed in 124 patients (50%) who had less distant metastasis and more hypertension. Thirty patients received statin for hyperlipidemia. Overall survival was 13.3 versus 10.0 months with and without DM (P = 0.084), but hazard ratio of DM was 1.05 (P = 0.758) in the multivariate analysis. Subgroup analysis of diabetic patients, but not in non-diabetic patients, demonstrated use of statins (hazard ratio, 0.40; P = 0.010) as a prognostic factor, as well as distant metastasis, performance status, combination therapy with gemcitabine and S-1, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. No antidiabetic medications were prognostic factors. CONCLUSIONS: Neither DM nor antidiabetic treatment had prognostic impact on advanced pancreatic cancer. Statin use was associated with better survival in the diabetic patients.

One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve.

BACKGROUND: Transcatheter aortic valve implantation was developed to provide a therapeutic option for patients considered to be ineligible for, and to mitigate mortality and morbidity associated with, high-risk surgical aortic valve replacement. METHODS AND RESULTS: The Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry was designed to assess initial post commercial clinical transcatheter aortic valve implantation results of the Edwards SAPIEN valve in consecutive patients in Europe. Cohort 1 consists of 1038 patients enrolled at 32 centers. One-year outcomes are presented. Patients with the transapical approach (n=575) suffered more comorbidities than transfemoral patients (n=463) with a significantly higher logistic EuroSCORE (29% versus 25.8%; P=0.007). These groups are different; therefore, outcomes cannot be directly compared. Total Kaplan Meier 1-year survival was 76.1% overall, 72.1% for transapical and 81.1% for transfemoral patients, and 73.5% of surviving patients were in New York Heart Association (NYHA) class I or II at 1 year. Combined transapical and transfemoral causes of death were cardiac in 25.1%, noncardiac in 49.2%, and unknown in 25.7%. Pulmonary complications (23.9%), renal failure (12.5%), cancer (11.4%), and stroke (10.2%) were the most frequent noncardiac causes of death. Multivariable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as variables with the highest hazard ratios for 1-year mortality whereas carotid artery stenosis, hyperlipidemia, and hypertension were associated with lower mortality. CONCLUSION: The SOURCE Registry is the largest consecutively enrolled registry for transcatheter aortic valve implantation procedures. It demonstrates that with new transcatheter aortic techniques excellent 1-year survival in high-risk and inoperable patients is achievable and provides a benchmark against which future transcatheter aortic valve implantation cohorts and devices can be measured.

Perioperative statin therapy reduces mortality in normolipidemic patients undergoing cardiac surgery.

OBJECTIVE: Statins might have pleiotropic effects, independent of their ability to reduce lipid levels. Recent data have suggested that statins improve early survival and cardiovascular outcomes after coronary artery bypass graft surgery. The effectiveness of statin therapy in normolipidemic cardiac surgery patients is as yet unclear. METHODS: We evaluated 3056 consecutive patients who had undergone cardiac surgery between April 2004 and April 2009. Perioperative statin therapy was defined as continued treatment both before (≥ 6 months) and after the index surgery (included as a discharge medication). Hyperlipidemia (HL) was defined as a total cholesterol level greater than 200 mg/dL within 6 months before surgery. Four groups were analyzed: (1) statin-untreated normolipidemic (NL-, n = 1052); (2) statin-treated normolipidemic (NL+, n = 206); (3) statin-untreated hyperlipidemic (HL-, n = 638); and (4) statin-treated hyperlipidemic (HL+, n = 1160) patients. Adjusted hazard ratios accounted for the known preoperative cardiac risk factors. Mortality was ascertained by retrospective database review and the Social Security Death Index. RESULTS: The mean follow-up was 2.2 years. The crude rate of 30-day mortality was 3.0% (32/1052), 0% (0/206), 8.0% (51/638), and 0.7% (8/1160) for the NL-, NL+, HL-, and HL+ groups, respectively. The overall all-cause crude mortality rate was 9.6% (101/1052), 3.9% (8/206), 17.2% (110/638), and 6.5% (75/1160) for the NL-, NL+, HL-, and HL+ groups, respectively. Statin therapy for NL patients undergoing cardiac surgery independently reduced the overall all-cause mortality (adjusted hazard ratio, 0.34; 95% confidence interval, 0.16-0.71; P = .004). CONCLUSIONS: Perioperative statin therapy was associated with reduced mid-term mortality for patients undergoing cardiac surgery, irrespective of their baseline lipid status. This clinical evidence suggests that the beneficial effects of statins might extend beyond their lipid-lowering ability.

Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias.

OBJECTIVE: To present the longest follow-up report of any lipid-atherosclerosis intervention trial. SUMMARY OF BACKGROUND DATA: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a secondary, clinical/arteriographic, randomized controlled trial, was the first lipid-atherosclerosis trial to demonstrate unequivocally that low density lipoprotein cholesterol reduction reduced the incidence of coronary heart disease death and myocardial infarction. METHODS: We report POSCH 25 years follow-up for overall mortality, specific cause of death, and certain subgroup analyses, as well as a prediction for increase in life expectancy derived from the POSCH database, supplemented by the 2006 National Death Index, 1989-2006. RESULTS: There were 838 patients randomized in POSCH (421 surgery, 417 control). At 25 years follow-up, the difference in the restricted mean survival and the logrank (Mantel-Haenszel) statistic was statistically significant, with survival probabilities of 0.57 (surgery) and 0.51 (controls). Cause of death data indicated a significant increase in cardiovascular deaths in the control group; cancer deaths were also greater in the control group but this was not significant. The most compelling subgroup analysis was a significant increase in survival, starting at 5 years after randomization, in the surgery group for patients with an ejection fraction > or = 50%, with relative probabilities of 0.61 (surgery) and 0.51 (control). The estimated incremental increase in life expectancy over more than 25 years of follow-up was 1.0 year overall and 1.7 years in the cohort with an ejection fraction > or = 50%. CONCLUSIONS: A 25-year mortality follow-up in POSCH shows statistically significant gains in overall survival, cardiovascular disease-free survival, and life expectancy in the surgery group compared with the control group.

Frequency of abnormal findings detected by comprehensive clinical evaluation at 1 year after allogeneic hematopoietic cell transplantation.

Consensus guidelines recommend various screening examinations for survivors after allogeneic hematopoietic cell transplantation (HCT), but how often these examinations detect abnormal findings is unknown. We reviewed the medical records of 118 patients who received comprehensive, standardized evaluations at 1 year after allogeneic HCT at Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance. Abnormal findings were common, including moderate to severe pulmonary dysfunction (16%), fasting hyperlipidemia (56%), osteopenia (52%), osteoporosis (6%), and active chronic graft-versus-host disease (cGVHD) (64%). Recurrent malignancy (4%) and cGVHD (29%) were detected in previously unsuspected cases. Only 3% of patients had no abnormal findings. We conclude that comprehensive evaluation at 1 year after allogeneic HCT detects a high prevalence of medical problems. Longer follow-up is needed to determine whether early detection and intervention affect later morbidity and mortality.

Results of a Markov model analysis to assess the cost-effectiveness of statin therapy for the primary prevention of cardiovascular disease in Korea: the Korean Individual-Microsimulation Model for Cardiovascular Health Interventions.

BACKGROUND: Although hyperlipidemia is well recognized as a risk factor for cardiovascular disease (CVD), there has been no appraisal of the economic impact of statin therapy in Korea. OBJECTIVE: The aim of this model analysis was to determine the cost-effectiveness of statin therapy versus no treatment for the primary prevention of CVD over a lifetime in Korea, from a health care system perspective. METHODS: We developed the Korean Individual-Microsimulation Model for Cardiovascular Health Interventions (KIMCHI), an epidemiologic and economic Markov model of first-onset CVD in Korea in which all individuals began the simulation in the health state alive without CVD, and moved among the 4 health states (alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes) in yearly cycles for any specified time horizon, up to 40 years. KIMCHI was populated with 372 subjects from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) who were aged > or =45 years, did not have a history of myocardial infarction or ischemic stroke, and met current Korean reimbursement criteria for treatment with lipid-lowering medications. The probability of first-onset CVD was estimated for each study participant individually, based on an Asian population-specific risk equation that relied on an individual's sex, age, serum total cholesterol, systolic blood pressure, current smoking status, diabetes mellitus status, and body mass index. Statin treatment was represented by a hybrid of atorvastatin and simvastatin (the most popular statins in Korea), the lipid-modifying effects of which were de rived from a published meta-analysis. Data regarding utilities and costs of CVD (both those covered and not covered by insurance) were derived from published local sources. RESULTS: In the base case, the estimated incremental costutility ratio was 15,134,284 Korean won (KRW) per quality-adjusted life-year (QALY) gained, and the estimated incremental cost-effectiveness ratio was 20,657,829 KRW per life-year gained (LYG) (1200 KRW approximately US $1). Based on a willingness-to-pay (WTP) threshold of 30 million KRW per QALY saved, there was a 93.7% probability that statin therapy would be cost-effective. Given a WTP threshold of 20 million KRW per QALY, there was a 53.8% probability of being cost-effective. The probabilities at WTP thresholds of 30 and 20 million KRW per LYG were 62.4% and 25.8%, respectively. CONCLUSIONS: Based on this analysis using data from the 2005 KNHNES and the KIMCHI model, statin therapy is likely to be cost-effective for the primary prevention of CVD among Koreans aged > or =45 years. The probability of being cost-effective was greater at a threshold of 30 million KRW per QALY (93.7%) than at 20 million KRW per QALY (53.8%).

Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke.

OBJECTIVE: To evaluate the impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke patients. METHODS: We prospectively investigated complications for all the consecutive acute ischaemic stroke patients admitted within 7 days from onset in four university hospitals during a 1-year period. Baseline data and 3-month outcomes were collected. Poor outcome was defined as a modified Rankin Scale score 3-6. RESULTS: A total of 1 254 patients were recruited: 264 (21.1%) and 303 (24.2%) patients experienced one or more neurological and medical complications, respectively. The most common complications were ischaemic stroke progression (17.1%) and pneumonia (12.0%). Of 1 233 patients with available 3-month outcomes, 34.9% had a poor outcome. Multivariate analysis revealed that neurological (odds ratio, 95% confidence interval; 5.47, 3.63-8.24) and medical (3.47, 2.30-5.23) complications were independent predictors of the poor outcome. For the individual complications, ischaemic stroke progression (7.48, 4.73-11.84), symptomatic hemorrhagic transformation (3.57, 1.33-9.54), pneumonia (4.44, 2.20-8.99), extracranial bleeding (4.45, 1.88-10.53), and urinary tract infection (2.72, 1.32-5.60) were independently associated with the poor outcome. CONCLUSION: Outcome after ischaemic stroke is adversely influenced by complications, especially ischaemic stroke progression, symptomatic hemorrhagic transformation, pneumonia, extracranial bleeding, and urinary tract infection. Interventions to prevent those complications might improve ischaemic stroke outcome.