Tatu A. Miettinen

Bio: Tatu A. Miettinen is an academic researcher from University of Helsinki. The author has contributed to research in topics: Cholesterol & Sterol. The author has an hindex of 75, co-authored 382 publications receiving 30367 citations. Previous affiliations of Tatu A. Miettinen include Jorvi Hospital & University of Turku.

Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population

Abstract: Background Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia. Methods We conducted a one-year, randomized, double-blind study in 153 randomly selected subjects with mild hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the control group), and 102 consumed margarine containing sitostanol ester (1.8 or 2.6 g of sitostanol per day). Results The margarine containing sitostanol ester was well tolerated. The mean one-year reduction in serum cholesterol was 10.2 percent in the sitostanol group, as compared with an increase of 0.1 percent in the control group. The difference in the change in serum cholesterol concentration between the two groups was -24 mg per deciliter (95 percent confidence interval, -17 to -...

Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population

Abstract: To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols, these noncholesterol sterols, fatty acids, and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a randomly selected Finnish male population sample of 100 subjects, aged 50 years, who had normal dietary habits. Serum levels of cholesterol precursors, desmosterol and lathosterol (in terms of micrograms/mg cholesterol), were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein (HDL) cholesterol, and positively related to overall cholesterol synthesis and serum very low density lipoprotein (VLDL) cholesterol. Serum levels of the plant sterols, campesterol and sitosterol, exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat, the linoleic acid contents of plasma and dietary lipids, the amount of dietary plant sterols (as indicated by fecal output), fractional and absolute absorption of dietary cholesterol, and HDL cholesterol, but were inversely related to the overall cholesterol synthesis and VLDL cholesterol. Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption, dietary plant sterols, and biliary cholesterol secretion, and that of sitosterol with dietary plant sterols, cholesterol synthesis, fractional cholesterol absorption, and biliary cholesterol secretion. Thus, the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and, since gas liquid chromatographic determination of these sterols is quite simple, their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies.

Lipoprotein Changes and Reduction in the Incidence of Major Coronary Heart Disease Events in the Scandinavian Simvastatin Survival Study (4S)

Abstract: Background—The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides ≤2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. Methods and Results—The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, an...

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Prediction of Coronary Heart Disease Using Risk Factor Categories

Abstract: Background—The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. Methods and Results—This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P,.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, ’28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal ($130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ($200 mg/dL) was 27% in men and 34% in women. Conclusions—Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD. (Circulation. 1998;97:1837-1847.)

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Abstract: Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S2 The goals of the …

Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines

Abstract: The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction

Abstract: Background Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. It has been debated whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions. Methods To address this issue, we compared the seven-year incidence of myocardial infarction (fatal and nonfatal) among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects, all from a Finnish population-based study. Results The seven-year incidence rates of myocardial infarction in nondiabetic subjects with and without prior myocardial infarction at base line were 18.8 percent and 3.5 percent, respectively (P<0.001). The seven-year incidence rates of myocardial infarction in diabetic subjects with and without prior myocardial infarction at base line were 45.0 percent and 20.2 percent, respectively (P<0.001). The hazard ratio for death from coronary heart di...