Comorbidities and survival of multiple myeloma patients diagnosed in Finland between 2000 and 2021.

Advances in treatment have improved the survival of multiple myeloma (MM) patients, but the disease remains incurable. Here, in this nationwide retrospective real-world evidence (RWE) study, we report the patient characteristics, incidence, overall survival outcomes, comorbidities, and healthcare resource utilization (HCRU) of all adult MM patients diagnosed between 2000 and 2021 in Finland. A total of 7070 MM patients and their 21,210 age-, sex- and region-matched controls were included in the analysis. The average MM incidence doubled from 4.11 to 8.33 per 100,000 people during the follow-up. The average age-standardized incidence also showed a significant increase over time (2.51 in 2000 to 3.53 in 2021). An increase in incidence was particularly seen in older population, indicative of improved diagnosis praxis. The median overall survival (mOS) of the MM patients and their matched controls was 3.6 and 15.6 years, respectively. The mOS of all MM patients increased significantly from 2.8 years (2000-2004) to 4.4 years (2017-2021) during the follow-up period. Distinctively, in patients who received autologous stem cell transplantation (ASCT), the mOS was 9.2 years, while in patients who did not receive ASCT, the mOS was only 2.7 years. MM patients showed more comorbidities at index and increased HCRU than their matched controls. The longer median survival and decreased risk of death indicate improved treatment outcomes in MM patients in Finland.

Comorbidity characteristics of multiple myeloma patients diagnosed in Finland 2005-2016.

Multiple myeloma (MM) patients are predominantly elderly with comorbidities that have an impact on patient mortality and treatment decisions. We previously reported the patient characteristics and overall survival outcomes of the Finnish MM cohort diagnosed between 2005 and 2016 in a nationwide retrospective registry study comprising 3,851 adults. Here, we report detailed comorbidity characteristics for this real-world Finnish MM population at cohort entry and during follow-up. Data on diagnoses and causes of death were obtained from Finnish healthcare data registries and interrogated using various multistate time-to-event models. In the year preceding MM diagnosis, comorbidities (as per Charlson Comorbidity Index definition) were recorded in 38.0% of the cohort, of which 27.9% presented with pre-existing cardiovascular disease (CVD) and 4.8% had suffered a major adverse cardiac event (MACE). At 2 years post-MM diagnosis, cumulative incidence for CVD and MACE more than doubled to 57.1% and 11.4%, respectively, and only 31.9% of the cohort remained CVD-free. Prevalent secondary malignancies were recorded in 16.8% of the patient population at MM diagnosis, with cumulative incidence increasing steadily to 27.5% at 2 years and 33% at 5 years post-diagnosis. The main cause of mortality attributed to MM, CVD, secondary malignancy, or other causes remained stable throughout the follow-up, at an average of 74.2%, 9.4%, 9.8%, and 6.5%, respectively. Prevalence of CVDs and secondary malignancies is high in Finnish patients at MM diagnosis, with older male patients suffering from higher MACE and mortality risk. Proper recording and management of comorbidities alongside novel treatments remain crucial for optimal MM management.

Characteristics and survival trends in Finnish multiple myeloma patients-a nationwide real-world evidence study.

Current understanding of the epidemiology and outcomes for patients with multiple myeloma in Finland is scarce due to lack of comprehensive real-world evidence in clinical practice. The aim of this study was to gain understanding of epidemiological characteristics and treatment and survival outcomes by utilizing multiple real-world data sources with information of adults treated for active multiple myeloma (MM) during years 2005-2016 in Finland. A total of 3851 adult MM patients with C90.0 diagnosis fulfilling all inclusion criteria were included in the analysis. The average myeloma incidence was six cases per 100,000, which slightly increased (p = 0.011) during the follow-up. The age-standardized incidence was three cases per 100,000 in the years 2005-2016. On average, 25% of patients received autologous stem cell transplantation (ASCT), and this proportion increased during the years 2005-2015 from 17 to 30%. The majority of patients under 65 years of age received ASCT treatment (60.5%), whereas only 8.7% of patients 65 years of age or older were treated with ASCT. The net median overall survival improved by approximately 5 months from 2005-2010 (3.44 years) to 2011-2016 (3.89 years); after adjusting for covariates, this presented an annual 4% reduction in the risk of death. Longer median survival and decreased risk of death indicate improved treatment outcomes from 2005 to 2016 among adult MM patients in Finland.

Parenteral plant sterols and intestinal failure-associated liver disease in neonates.

OBJECTIVES: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure-associated liver disease (IFALD) compared with children. METHODS: We recruited 28 neonates (mean age 50 days, range 28-126) and 11 children (6.9 y, 2.1-16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n=10) and children (n=22) served as controls. RESULTS: IFALD occurred more frequently among neonates (63%) than children (27%; P<0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P<0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P<0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r=0.472-0.636, P<0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r=0.529-0.688, P<0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P<0.05). CONCLUSIONS: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.

Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose and lipoprotein metabolism. However, the metabolism of cholesterol in NAFLD remains unexplored. We investigated how fatty liver influences cholesterol metabolism in 242 non-diabetic subjects. METHODS: Liver fat content was measured with proton magnetic resonance spectroscopy. Cholesterol metabolism was assayed with serum non-cholesterol sterols, surrogate markers of cholesterol synthesis and absorption. The analyses were performed with gas-liquid chromatography. RESULTS: A total of 114 subjects had NAFLD and 128 subjects had normal liver fat content. Non-cholesterol sterols reflecting cholesterol synthesis (cholestenol, desmosterol, and lathosterol) were higher, and those reflecting cholesterol absorption (cholestanol and plant sterols) were lower in subjects with NAFLD than in controls, independent of body mass index. Liver fat content was positively associated with markers of cholesterol synthesis (r = from 0.262 to 0.344, p < 0.001 for all) and inversely associated with markers of cholesterol absorption (r = from -0.299 to -0.336, p < 0.001 for all). In the entire study group, synthesis and absorption markers were interrelated, indicating that the homeostasis of cholesterol metabolism was maintained. LDL cholesterol was similar in the two groups. CONCLUSIONS: We demonstrated that although LDL cholesterol concentrations are unchanged, cholesterol metabolism in NAFLD is characterized by increased synthesis and diminished absorption of cholesterol. These changes are associated with liver fat content independent of body weight.

Effects of long-term parenteral nutrition on serum lipids, plant sterols, cholesterol metabolism, and liver histology in pediatric intestinal failure.

BACKGROUND AND OBJECTIVE: Plant sterols (PS) in parenteral nutrition (PN) may contribute to intestinal failure-associated liver disease. We investigated interrelations between serum PS, liver function and histology, cholesterol metabolism, and characteristics of PN. PATIENTS AND METHODS: Eleven patients with intestinal failure (mean age 6.3 years) receiving long-term PN were studied prospectively (mean 254 days) and underwent repeated measurements of serum lipids, noncholesterol sterols, including PS, and liver enzymes. PS contents of PN were analyzed. Liver biopsy was obtained in 8 patients. Twenty healthy children (mean age 5.7 years) served as controls. RESULTS: Median percentage of parenteral energy of total daily energy (PN%) was 48%, including 0.9 g · kg(-1) · day(-1) of lipids. Respective amounts of PN sitosterol, campesterol, avenasterol, and stigmasterol were 683, 71, 57, and 45 µg · kg(-1) · day(-1). Median serum concentrations of sitosterol (48 vs 7.5 µmol/L, P < 0.001), avenasterol (2.9 vs 1.9, P < 0.01), stigmasterol (1.9 vs 1.2, P < 0.005), but not that of campesterol (9.8 vs 12, P = 0.22), were increased among patients in relation to controls, and correlated with PN% (r = 0.81-0.88, P < 0.005), but not with PN fat. Serum cholesterol precursors were higher in patients than in controls. Serum liver enzymes remained close to normal range. Glutamyl transferase correlated with serum PS (r = 0.61-0.62, P < 0.05). Liver fibrosis in 5 patients reflected increased serum PS (r = 0.55-0.60, P = 0.16-0.12). CONCLUSIONS: Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.

Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study.

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 +/- 7 vs. 136 +/- 3 10(2) mumol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = -0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.

Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis.

Transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N(1)-acetyltransferase (SSAT) have significantly reduced plasma total cholesterol levels. In our study, we show that low cholesterol levels were attributable to enhanced bile acid synthesis in combination with reduced cholesterol absorption. Hepatic cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme catalyzing the conversion of cholesterol to bile acids, plays an important role in the removal of excess cholesterol from the body. We suggest that by reducing activity of Akt activated polyamine catabolism increased the stability and activity of peroxisome proliferator-activated receptor gamma co-activator 1alpha, the critical activator of CYP7A1. This is supported by our finding that the treatment with SSAT activator, N (1) ,N(11)-diethylnorspermine, reduced significantly the amount of phosphorylated (active) Akt in HepG2 cells. In summary, activated-polyamine catabolism is a novel mechanism to regulate bile acid synthesis. Therefore, polyamine catabolism could be a potential therapeutic target to control hepatic CYP7A1 expression.

Leisure-time physical activity, cardiovascular risk factors and mortality during a 34-year follow-up in men.

UNLABELLED: The inverse relationship between physical activity and mortality may be confounded by socioeconomic factors, cardiovascular risk factors and inverse causality. We investigated long-term association between self-reported regular physical activity and mortality in a socioeconomically homogeneous, initially healthy middle-aged (mean age 47) male cohort (the Helsinki Businessmen Study). In 1974, the men were assessed with questionnaires, clinical and laboratory examinations. Cardiovascular disease (CVD) risk factors (including body mass index [BMI], age, cholesterol, glucose, systolic blood pressure and smoking) and details of physical activity of 782 men were available. Leisure time physical activity was collapsed into 3 categories: low (n = 148), moderate (n = 398) and high activity (n = 236). Physical activity was also briefly assessed in questionnaire surveys in 1985-1986 and in 2000. Total mortality up to 2007 was retrieved from the Central Population Register. Altogether 295 men (37.7%) died during the 34-year follow-up, and leisure-time physical activity was significantly related to mortality in a step-wise manner: 45.9% (n = 68), 37.7% (n = 150), and 32.6% (n = 77) died in the low, moderate, and high activity groups, respectively (P < 0.001). With high activity group as referent and adjusted for midlife CVD risk, perceived health and fitness at baseline, hazard ratio for total mortality was 1.21 (95% confidence interval: 0.90, 1.62), and 1.61 (95% confidence interval: 1.13, 2.30) in the moderate and low activity groups, respectively. CONCLUSION: During the 34-year follow-up, leisure-time physical activity in initially healthy middle-aged men had a graded association with reduced mortality that was independent of CVD risk, glucose and BMI.

Very high plant stanol intake and serum plant stanols and non-cholesterol sterols.

BACKGROUND: Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. AIM OF THE STUDY: We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. METHODS: In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. RESULTS: When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. CONCLUSIONS: Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.

Explaining the obesity paradox: cardiovascular risk, weight change, and mortality during long-term follow-up in men.

AIMS: To examine life-long weight trajectories behind the 'obesity paradox', and whether cardiovascular disease (CVD) risk contributes. METHODS AND RESULTS: Cardiovascular disease risk and body mass index (BMI) at mean ages of 25, 47 (year 1974), and 73 years (year 2000) were available of a socioeconomically homogenous sample of 1114 men, without chronic diseases and diabetes in 1974. Overweight was defined as BMI > 25 kg/m(2), and 7-year mortality (2000-06) from the mean age of 73 years determined (188 deaths). Between 1974 and 2000, 44.3% (n = 494) were constantly overweight, 31.0% (n = 345) constantly normal weight, 12.2% (n = 136) moved from normal to overweight, and 12.5% (n = 139) moved from overweight to normal. The last group had highest CVD risk in midlife, and in late life more co-morbidities and greatest total mortality (P < 0.001). Adjusted mortality hazard ratio was 2.0 (95% confidence interval, CI 1.3-3.0; constantly normal weight group as referent). The hazard ratio remained similar (1.9, 95% CI 1.2-3.0) after adjustment for prevalent diseases in 2000. CONCLUSION: In old age, both normal weight and overweight men are a mixture of individuals with different weight trajectories during their life course. Overweight and high-CVD risk in midlife with subsequent weight decrease predict the worst prognosis in late life.

The effects of statins and sitosterols: benefit or not?

Statins reduce plasma plant sterol concentrations and, less consistently, their ratios to cholesterol in short-term studies. They most likely accomplish this by decreasing their transport protein levels. In long-term treatment with large doses of effective statins, serum plant sterol concentrations and frequently their ratios to cholesterol are consistently increased, especially with high, as opposed to low, baseline ratios. Enhanced intestinal absorption, decreased biliary secretion, and reversed cholesterol and plant sterol transport could explain these findings. However, statin treatment increases plant sterol ratios in serum and also in arterial plaques of endarterectomized patients. No trials of functional foods with plant sterols or stanols are available for coronary heart disease, even though their combination with statins effectively reduces low-density lipoprotein cholesterol. Plant sterols increase and plant stanols decrease serum plant sterols. Long-term statin treatment lowers coronary heart disease events only in patients with low baseline plant sterols who have high cholesterol synthesis. No convincing evidence is available that statin-induced phytosterolemia worsens atherosclerosis.

Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation.

Polymorphisms of the ABCG5 and ABCG8 genes interfere with cholesterol absorption and synthesis. We determined whether common polymorphisms of these genes regulate the responses of serum cholesterol and vascular function during long-term inhibition of cholesterol absorption. Mildly to moderately hypercholesterolaemic subjects (n 282) completed a 1-year study consuming plant stanol or sterol ester (2 g stanol or sterol) or control spread. Serum cholesterol and non-cholesterol sterols, markers of cholesterol absorption and synthesis, and variables of vascular function and structure were analysed in relation to common polymorphisms of ABCG5 and ABCG8. At baseline, subjects with the 54K allele of ABCG8 had higher brachial endothelial-dependent flow-mediated dilatation than those without it (5.79 (se 0.31) v. 4.46 (se 0.44) %; P = 0.049), and subjects with the 632V allele of ABCG8 had larger brachial artery diameter than those without it. Polymorphisms of ABCG5 and ABCG8 were neither associated with serum cholesterol reduction nor changes in cholesterol metabolism or in vascular function. However, in subjects with the 400K allele of ABCG8, intima media thickness (IMT) was increased in all groups more than in those without it (P < 0.05). In conclusion, serum cholesterol lowering with absorption inhibition was not associated with polymorphic sites of ABCG5 and ABCG8. However, regulation of baseline cholesterol metabolism and vascular function and structure, and IMT progression during 1 year seemed to share some of the common polymorphic sites of these genes, suggesting a gene-regulated interaction between cholesterol metabolism and vascular function and structure.

Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men.

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0.05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0.05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0.308 to+0.383; P range 0.214-0.011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0.713 to+0.893; P < 0.05 for each), but only during HD (r+0.594; P = 0.015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.

Plant stanol ester consumption and arterial elasticity and endothelial function.

We evaluated whether plant stanol esters mixed with different vegetable oil spreads improved arterial health. A total of 200 adults with serum cholesterol >5 mmol/l were randomised to consume camelina, rapeseed or sunflower oil spread with stanol (2 g/d) ester or sunflower oil spread without stanol ester (controls) for 3 months. Non-invasive ultrasound was used to measure carotid artery compliance (CAC) and brachial artery flow-mediated endothelial dependent vasodilatation (FMD) at baseline and after the intervention as markers of arterial health. Plant stanol esters reduced LDL-cholesterol by 9 % compared with controls (P < 0.001) similarly in the different treatment groups. In the combined treatment groups (n 147), CAC or FMD were not changed from controls (n 47). In a subgroup analysis, division of subjects at baseline into below and over sex-specific 50th percentiles of CAC and FMD revealed that low CAC was improved from 1.23 to 1.59 % per 10 mmHg in the treatment group (n 69), and from 1.42 to 1.47 % per 10 mmHg in controls (n 25), (P = 0.0035 between groups). Low FMD was improved from 6.9 % to 8.6 % in the treatment group (n 73) and from 6.6 % to 6.8 % in controls (n 24) (P = 0.05 between groups). In the respective high-median groups, CAC and FMD were not changed in spite of significantly lowered LDL-cholesterol. In conclusion, consumption of plant stanol ester for 3 months had no overall significant effect on arterial elasticity and endothelial function. A controlled study is needed to test whether beneficial changes are obtained in subjects with initially reduced arterial elasticity and endothelial function.

Effect of parenteral serum plant sterols on liver enzymes and cholesterol metabolism in a patient with short bowel syndrome.

Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the concentrations of sitosterol, campesterol, and stigmasterol were 4361, 1387, and 378 microg/dL, respectively, and serum liver enzyme values were >or= 2.5 times above upper limit of normal. After changing to olive oil-based intravenous fat emulsion (20-35 g/d, plant sterols 37-65 mg/d), concentrations decreased to 2148 to 2251 microg/dL for sitosterol, 569-297 microg/dL for campesterol, and 95-55 microg/dL for stigmasterol. Concomitantly, liver enzyme values decreased to 1.4 to 1.8 times above upper limit of normal at the end of follow-up. The nutrition status of the patient improved. The amount of plant sterols in lipid emulsion affects serum liver enzyme levels more than the amount of lipid.

Type 2 diabetes and treatment intensification in primary care in Finland.

AIM: To identify how the electronic health record (EHR) systems and national registers can be used for research purposes. We focused on how the primary care physicians adhere to clinical guidelines. METHODS: Study population included incident type 2 diabetes patients from four selected regions. Data were collected in two phases. At the first phase study cohort was identified using the prescription registers of the Social Insurance Institution (SII) and EHR systems used within the study regions. At second phase, data were collected from SII's registers, local EHR systems, the hospital discharge and the primary care registers of National Institute for Health and Welfare. RESULTS: Metformin was the most common choice as first drug. Among all study patients, 8375 (76.0%) started metformin monotherapy or combinations. The treatment was intensified at variable levels of HbA1c depending on the area. DPP4-inhibitors were by far the most common agent for treatment intensification. Sulphonylureas were used less often than basal insulin as the second-line agent. The use of DPP4-inhibitors increased between years 2009-2010, when first DPP4-inhibitor received reimbursement and this class became dominant drug for treatment intensification increasingly thereafter. CONCLUSIONS: The EHR systems and national registers can be used for research purposes in Finland. The realization of diabetes treatment national guidelines are followed in primary care to a large extent. However, the subsequent intensification of therapy was delayed and occurred at elevated Hba1c levels.

Altered hepatic lipid status and apolipoprotein A-I metabolism in mice lacking phospholipid transfer protein.

The effect of PLTP deficiency on hepatic lipid status and apolipoprotein A-I (apoA-I) biosynthesis in PLTP knockout (PLTP-KO) mice was investigated. PLTP-KO mice exhibited a marked reduction in HDL levels, but also increased triglycerides (TG), phospholipids (PL), and cholesterol in very-low-density lipoproteins (VLDL). Both male and female PLTP-KO mice displayed increased hepatic PL and decreased TG, and in the females, increased hepatic cholesterol was also detected. Primary hepatocytes from PLTP-KO mice displayed a different PL molecular species composition to the wild type (WT) controls, with prominent changes being a reduction of long chain fatty acid-containing and an increase of medium chain mono- or di-unsaturated fatty acid containing PL species. Cultured PLTP-KO hepatocytes synthesized and secreted apoA-I in similar quantities as the WT cells. However, the apoA-I secreted by PLTP-KO hepatocytes contained less choline PL, differing also in phosphatidylcholine/sphingomyelin ratio and fatty acyl species composition when compared to apoA-I from WT hepatocytes. Furthermore, the PLTP-KO-derived PL-deficient apoA-I was less stable in the hepatocyte culture medium than that produced by WT cells. These results demonstrate a complex regulatory role of PLTP in serum and liver lipid homeostasis, as well as in the formation of nascent apoA-I-PL complexes from the liver.

Alcoholic beverage preference, 29-year mortality, and quality of life in men in old age.

BACKGROUND: Harms of excessive alcohol consumption are obvious, but moderate wine consumption is frequently advocated for prevention of cardiovascular diseases. We compared 29-year mortality and quality of life in old age by alcoholic beverage preference (beer, wine, or spirits) in a cohort of men whose socioeconomic status was similar in their adult life. METHODS: In 1974, cardiovascular risk factors and beverage preference were assessed in 2468 businessmen and executives aged 40-55 years. Of them, 131 did not use alcohol, 455 did not report a single preference, and 694, 251, and 937 preferred beer, wine, and spirits, respectively. Quality of life with a RAND-36 Short Form (SF)-36 instrument was surveyed in 2000 in survivors. Mortality was retrieved from registers during the 29-year follow-up. RESULTS: Alcoholic beverage preference tracked well during the follow-up. Total alcohol consumption was not significantly different between preference groups. Men with wine preference had the lowest total mortality due to lower cardiovascular mortality. With the spirits group as the reference category and age, cardiovascular risk factors, and total alcohol consumption as covariates, wine drinkers had a 34% lower total mortality (relative risk 0.66; 95% confidence interval, 0.45-0.98); relative risk for beer preferers was 0.91 (95% confidence interval, 0.68-1.14). In 2000, wine preferers had the highest scores in all RAND-36 scales; general health (p =.007) and mental health (p =.01) were also significantly different. CONCLUSION: In this male cohort from the highest social class, wine preference was associated with lower mortality and better quality of life in old age. Mortality advantage was independent of overall alcohol consumption and cardiovascular risk factors, but contributing personal characteristics or early life differences cannot be excluded.

Blood glucose and the metabolism of cholesterol in coronary patients with and without simvastatin treatment.

BACKGROUND AND AIM OF THE STUDY: Association of blood glucose with cholesterol metabolism and with cholesterol lowering during simvastatin treatment has not been studied earlier in hypercholesterolemic subjects with coronary heart disease. METHODS: Baseline blood glucose was compared with cholesterol synthesis (e.g. ratios of squalene and lathosterol) and absorption (e.g. sitosterol ratio) without and with simvastatin for one year in 806 non-diabetes Finnish subjects of the Scandinavian Simvastatin Survival Study. RESULTS: Baseline blood glucose was positively correlated with the baseline synthesis and negatively with the absorption of cholesterol, and positively with the synthesis/absorption ratio (e.g. p=0.001 for lathosterol/sitosterol). Simvastatin decreased serum cholesterol by about 29% irrespective of glucose level, cholesterol synthesis by up to 34%, especially in the highest glucose quartile, and increased cholesterol absorption by up to 49%, especially in the lowest glucose quartile (p<0.01 for all). The one-year synthesis/absorption ratio was decreased proportionately to the baseline glucose, e.g. for lathosterol/sitosterol by over 40% (p<0.001) in different glucose quartiles (p<0.001 between quartiles). CONCLUSIONS: Baseline blood glucose level is related positively to cholesterol synthesis and negatively to that of absorption. Despite a marked glucose-related decrease in cholesterol synthesis with simvastatin, serum cholesterol reduction was not dependent on the baseline glucose level.