Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement.

Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

Lifestyle changes to prevent cardio- and cerebrovascular disease at midlife: A systematic review.

Cardio- and cerebrovascular diseases are leading causes of death and morbidity in ageing populations. While numerous cohort studies show inverse associations of presumably healthy lifestyles and cardiovascular risk factors, the causal link to many modifiable behaviors is still insufficiently evidence-based. Because of bias of studies and heterogeneity of results, we performed a systematic review of meta-analyses of randomized controlled trials and observational studies on lifestyle patterns including nutrition, physical activity, smoking, and weight versus incidence and mortality of cardio- and cerebrovascular diseases. A search string retrieved 624 references in PubMed covering the last five years. Two researchers screened titles and abstracts independently but with equivalent results. Nineteen references met the inclusion criteria. Results affirm that high adherence to plant-based diets, including components such as fruits, vegetables, legumes, whole grains, low-fat dairy, olive oil, nuts, and low intake of sodium, sweetened beverages, alcohol, and red and processed meats, results in lower risk of vascular outcomes in a dose-dependent manner. Physical activity quantified as walking pace or cardiorespiratory fitness yielded an inverse effect on stroke. Health measures such as smoking status, BMI and increase in body weight are associated with substantial risk of the incidence of and mortality from cardio- and cerebrovascular diseases, while strong adherence to an overall prudent lifestyle lowered the risk of cardiovascular disease by 66 % and that stroke by 60 %. In summary, increasing numbers of and adherence to health behaviors may markedly lower the burden of cardio- and cerebrovascular diseases. However, future research should focus on randomized controlled trials to test for causal relationships.

The impact of nutrition on the development and progression of peripheral artery disease: A systematic review.

BACKGROUND & AIMS: This systematic review sought to identify and summarize existing evidence for the impact of nutrition on the development, progression, and outcomes of peripheral artery disease (PAD). METHODS: We performed a systematic literature search of available studies published between January 1974 and December 2019. Randomized controlled trials (RCT), observational studies, and cross-sectional studies reporting either the primary or secondary prevention of PAD with nutritional intake were included. The quality assessment was performed for the RCTs, without pooling a meta-risk estimate. RESULTS: Among a total of 8502 records screened, 186 full texts were assessed for eligibility, and 82 studies (30% RCT) were analyzed. The nutrients were structured in fruits, vegetables and antioxidants, fats and oils, dietary fiber, meat, proteins, vitamins and trace elements, and diets and lifestyle. The findings of the current systematic review indicate that the Mediterranean diet, nuts, and polyunsaturated fat are associated with a lower incidence of PAD and saturated fat, cholesterol, and processed meat were associated with higher rates of cardiovascular events in patients suffering from PAD. CONCLUSIONS: The current review found evidence of a beneficial impact of the Mediterranean diet including nuts in this target population. More RCTs and high-quality registries are needed that focus on nutritional habits among patients with PAD to design appropriate preventive programs.

Knowledge as to cholesterol reduction and use of phytosterol-enriched dietary foods in the general population: Insights from the Hamburg City Health Study.

BACKGROUND AND AIMS: Dietary approaches to lowering cholesterol appear to be common knowledge. However, the marketing of phytosterol-enriched products and their recommendation by guidelines for individuals at increased risk of cardiovascular disease have given rise to concern, since phytosterols may be atherogenic and inappropriately used by healthy individuals of higher social status at low cardiovascular risk. Hence, we have investigated awareness of cholesterol lowering lifestyle measures and attitudes towards consumption of phytosterol-enriched foods. METHODS: Data from validated questionnaires supplemented by queries on cholesterol lowering and phytosterol-enriched products were analyzed using data of 7223 participants of the Hamburg City Health Study, an ongoing cohort study of the general population aged 45-74 years. RESULTS: 95.9% of the participants agreed that lifestyle may lower cholesterol and 76.6% claimed knowledge of measures that lower plasma cholesterol. As to effective approaches, 80.2% suggested physical activity, 67.8% reducing dietary fat, followed by sugar-sweetened beverages or stress, increasing water consumption, or dietary fiber and only 16.2% stated statins and 9.3% phytosterol-enriched products. Compared to nonusers, the 2.0% female and 2.8% male individuals regularly using phytosterol-enriched products had a lower educational status, higher cardiovascular risk, but no difference in income and were characterized by adverse dietary habits. The study has been registered in ClinicalTrial.gov (NCT03934957). CONCLUSIONS: In the general population awareness of hypercholesterolemia is high but knowledge on how to lower plasma cholesterol does not necessarily follow scientific evidence. There is a trend towards the use of phytosterol-enriched products by individuals at increased cardiovascular risk independent of income.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Carotid intima-media thickness and cardiovascular risk factors in healthy volunteers.

BACKGROUND: Assessment of cardiovascular risk by scores lacks sensitivity and leaves the majority of future cardiovascular patients unidentified particularly individuals at low cardiovascular risk. The present analysis investigates into the correlation of carotid intima-media thickness (CIMT) and cardiovascular risk factors and derived scores as to the potential of improved cardiovascular risk prediction by combining the two. METHODS: The Stress, Atherosclerosis and ECG Study (STRATEGY) is a cross-sectional study of selectively healthy 107 women and 106 men without diagnosed and treated cardiovascular risk factors evenly distributed between 30 and 70 years. CIMT was determined by evaluating B-mode ultrasonograms offline according to a standardized protocol. The unpaired t-test was used to compare normal-distributed continuous variables, the Chi-squared test for normal-distributed categorical variables and the Mann-Whitney U test for non-normal distributed continuous variables. The association between risk prediction scores and CIMT was calculated by the Spearman rank correlation coefficient. Pearson correlation coefficient was used for the correlation between cardiovascular risk factors and CIMT. A multiple linear regression analysis was executed for the association of cardiovascular risk factors and CIMT. RESULTS: Age, systolic blood pressure, fasting glucose, total, LDL- and non-HDL-cholesterol and waist circumference were significantly associated with CIMT (each P ≤ 0.03). The Framingham Risk Score, the Prospective Cardiovascular Münster Study Score and the European Society of Cardiology Score correlated significantly but only moderately with CIMT. The Framingham Risk Score considering BMI correlated most strongly and predicted 27% of the CIMT variance in men and 20% in women. CONCLUSION: In individuals without overt cardiovascular risk factors and thus at low cardiovascular risk, CIMT and cardiovascular risk factors correlated only partially suggesting that combining CIMT and conventional risk factors or common derived scores may improve risk prediction in individuals at low cardiovascular risk. The clinical benefit as to cardiovascular events of such combined risk prediction needs to be explored in large prospective cohorts of still healthy low-risk volunteers. DRKS ID DRKS00015209 07/02/2019 retrospectively registered https://www.drks.de/drks_web/navigate.do?navigationId=resultsExt.

Peri- and postmenopause-diagnosis and interventions interdisciplinary S3 guideline of the association of the scientific medical societies in Germany (AWMF 015/062): short version.

This short version of the interdisciplinary S3 guideline "Peri- and Postmenopause-Diagnosis and Interventions" is intended as a decision-making instrument for physicians who counsel peri- and postmenopausal women. It is designed to assist daily practice. The present short version summarizes the full version of the guideline which contains detailed information on guideline methodology, particularly regarding the critical appraisal of the evidence and the assignment of evidence levels. The statements and recommendations of the full version of the guideline are quoted completely in the present short version including levels of evidence (LoE) and grades of recommendation. The classification system developed by the Centre for Evidence-based Medicine in Oxford was used in this guideline.

Joint Data Analysis in Nutritional Epidemiology: Identification of Observational Studies and Minimal Requirements.

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition.

Interaction of smoking and dietary habits modifying the risk of coronary heart disease in women: results from a case-control study.

BACKGROUND/OBJECTIVES: Smoking is a strong risk factor for coronary heart disease particularly in women. The risk may be aggravated by dietary habits, though. SUBJECTS/METHODS: The Coronary Risk for Atherosclerosis Study (CORA) compares dietary, lifestyle, biochemical, and clinical factors in 200 consecutive pre- and postmenopausal women with incident coronary heart disease to those of 255 age-matched population-based controls. A mixed logistic regression model was used to assess the possible interactions between smoking habits and dietary patterns. RESULTS: Each increase of 100 kcal energy intake per day was positively associated with coronary risk (OR 1.10, 95% CI 1.03-1.17; p = 0.006). Doubling the intake of alcohol and vegetables was negatively related with coronary risk (alcohol: OR 0.61, 95% CI 0.50-0.73; p < 0.001; vegetables: OR 0.50, 95% CI 0.032-0.080; p = 0.003). In contrast, doubling the intake of meat was associated with an increase of coronary risk, but only in smoking women (OR 2.61, 95%CI 1.58-4.29; p < 0.001). In smoking women a high meat-over-vegetable-ratio indicated an even higher risk (ratio of 2.0: OR 5.77, 95% CI 2.13-15.67; p < 0.001), while a low meat-over-vegetable-ratio did not have a significant impact on coronary risk (ratio of 0.5: OR 1.28, 95% CI 0,78-2.09). CONCLUSIONS: This explorative analysis of the CORA-study indicates that a high intake of meat is significantly associated with an increase in coronary risk particularly in smoking women, and may account for part of the unadjusted risk of smoking.

LDL-Cholesterol: Standards of Treatment 2016: A German Perspective.

Decreasing low-density lipoprotein cholesterol (LDL-C) is one of the few established and proven principles for the prevention and treatment of atherosclerosis. The higher the individual cardiovascular risk, the higher the benefit of lipid-lowering pharmacotherapy. Therefore, treatment options are chosen based on a patient's total cardiovascular risk. The latter depends not only on the levels of LDL-C but also on the presence of cardiovascular disease (CVD) and on the number and severity of other risk factors. Current guidelines recommend the lowering of LDL-C to 115 mg/dl (3 mmol/l) in patients with low and moderate risk. The LDL-C treatment target is <100 mg/dl (2.6 mmol/l) for patients at high risk and <70 mg/dl (1.8 mmol/l) for patients at very high risk. Although lifestyle measures remain a fundamental part of treatment, many patients require drug therapy to achieve their LDL-C targets. Statins are the drugs of choice, with other options including ezetimibe and the newly available monoclonal antibodies against PCSK9 (proprotein convertase subtilisin/kexin type 9). In some cases, bile acid-binding sequestrants and fibrates can also be considered. Nicotinic acid is no longer available in Germany. PCSK9 antibodies decrease LDL-C about 50-60 % and are well tolerated. Their effects on clinical endpoints are being investigated in large randomized trials. The aim of the present review is to summarize the current guidelines and treatment options for hypercholesterolemia. Moreover, we provide an appraisal of PCSK9 antibodies and propose their use in selected patient populations, particularly in those at very high cardiovascular risk whose LDL-C levels under maximally tolerated lipid-lowering therapy are significantly over their treatment target.

Nonalcoholic fatty liver disease is associated with excessive calorie intake rather than a distinctive dietary pattern.

We aimed to assess the dietary patterns associated with nonalcoholic fatty liver disease (NAFLD) and the efficacy of dietary interventions in a real-life setting at a tertiary medical center in Northern Germany.Clinical and laboratory data as well as data obtained by a semiquantitative food frequency questionnaire of 55 consecutive patients diagnosed with NAFLD were compared to an age and gender-matched cohort of 88 healthy individuals by univariate analysis. The efficacy of the dietary intervention was assessed in a subgroup of 24 NAFLD patients 6 months after receiving dietary advice. Macronutritional components of the diet were normalized for absolute daily energy intake.NAFLD patients consumed more calories per day as compared with healthy controls (P <0.001). The absolute amounts of most nutritional components ingested by NAFLD patients were higher than those of the controls. However, there were no significant differences with regards to the relative consumption of carbohydrates (P = 0.359), fat (P = 0.416), and fructose (P = 0.353) per 1000 kcal energy intake. NAFLD patients displayed a higher intake of glucose/1000 kcal (P = 0.041) and protein/1000 kcal (P = 0.009) but a lower intake of fibers/1000 kcal (P < 0.001) and mineral nutrients/1000 kcal (P = 0.001) than healthy controls. In the longitudinal analysis patients significantly reduced their caloric intake and their ALT levels improved 6 months after the dietary counselling (P < 0.001).Our data from a German real-life cohort demonstrate that dietary patterns of patients with NAFLD display great variability and little disease specificity, while the most distinctive feature compared with healthy controls was higher energy intake in NAFLD patients.

Treatment Options for Statin-Associated Muscle Symptoms.

BACKGROUND: About 4.6 million persons in Germany are now taking statins, i.e., drugs that inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. Statins lower the concentration of low-density lipoproteins (LDL) and thereby lessen the rate of cardiovascular events; the size of this effect depends on the extent of lowering of the LDL cholesterol concentration. Muscle symptoms are a clinically relevant side effect of statin treatment. METHODS: This review is based on pertinent publications retrieved by a selective literature search, and on the current recommendations of the European Atherosclerosis Society. RESULTS: At least 5% of patients taking statins have statin-associated muscle symptoms (SAMS). The etiology of SAMS is heterogeneous. SAMS may seriously impair quality of life and cause complications of variable severity, up to and including rhabdomyolysis (in about 1 in 100,000 cases). SAMS often lead to a reduction in the prescribed dose of the statin, while also negatively affecting drug adherence. More than 90% of patients with SAMS can keep on taking statins over the long term and gain the full clinical benefit of statin treatment after a switch to another type of statin or a readjustment of the dose or frequency of administration. If the LDL cholesterol concentration is not adequately lowered while the patient is taking a statin in the highest tolerable dose, combination therapy is indicated. CONCLUSION: SAMS are important adverse effects of statin treatment because they lessen drug adherence. Patients with SAMS should undergo a thorough diagnostic evaluation followed by appropriate counseling. In most cases, statins can be continued, with appropriate adjustments, even in the aftermath of SAMS.

Is postmenopausal hormone replacement therapy suitable after a cardio- or cerebrovascular event?

PURPOSE: Vascular disease is the leading cause of death in women. One-third of acute events affect women below age 60, when the prevalence of menopausal symptoms is high. This raises the question if hormone replacement therapy (HRT) may be an appropriate treatment for individual women although vascular disease is generally considered a contraindication. METHODS: Selective literature search was used for this study. RESULTS: In healthy women, HRT increases risks for venous thromboembolism and ischemic stroke, but for cardiovascular disease apparently only beyond 10 years after menopause or 60 years of age. Limited data in women with cardio or cerebrovascular disease have not demonstrated an increased risk for a vascular recurrent event, but for the first year after initiation. In HRT users affected by a cardiovascular event continuation of HRT has not been found to be associated with adverse outcome. Low dose estradiol--preferentially as transdermal patches, if necessary combined with metabolically neutral progestins--appears to convey lower risk. CONCLUSIONS: Safety data on HRT in survivors of cardiovascular events or ischemic stroke are limited, but exceptionally increased risk appears to be excluded. If off-label use of HRT is considered to be initiated or continued in women with cardio- or cerebrovascular disease, extensive counseling on the pros and cons of HRT is mandatory.

Familial hypercholesterolemia: developments in diagnosis and treatment.

BACKGROUND: Familial hypercholesterolemia (FH) is a congenital disorder of lipid metabolism characterized by a marked elevation of the plasma concentration of LDL (low-density lipoprotein) cholesterol beginning in childhood and by the early onset of coronary heart disease. It is among the commonest genetic disorders, with an estimated prevalence in Germany of at least 1 per 500 persons. METHOD: Review of pertinent literature retrieved by a selective search. RESULTS: FH is underdiagnosed and undertreated in Germany. It is clinically diagnosed on the basis of an elevated LDL cholesterol concentration (>190 mg/dL [4.9 mmol/L]), a family history of hypercholesterolemia, and early coronary heart disease, or the demonstration of xanthomas. The gold standard of diagnosis is the identification of the underlying genetic defect, which is possible in 80% of cases and enables the identification of affected relatives of the index patient. The recommended goals of treatment, based on the results of observational studies, are to lower the LDL cholesterol concentration by at least 50% or to less than 100 mg/dL (2.6 mmol/L) (for children: <135 mg/dL [3.5 mmol/L]). The target value is lower for patients with clinically overt atherosclerosis (<70 mg/dL [1.8 mmol/L]). Statins, combined with a health-promoting lifestyle, are the treatment of choice. Lipoprotein apheresis is used in very severe cases; its therapeutic effects on clinical endpoints and its side effect profile have not yet been documented in randomized controlled trials. CONCLUSION: Familial hypercholesterolemia is a common disease that can be diagnosed simply and reliably on clinical grounds and by molecular genetic testing. Timely diagnosis and appropriate treatment can lower the risk of atherosclerosis in heterozygous patients to that of the general population.