Cardiovascular risk factors and aortic valve stenosis: towards 10-year absolute risk charts for primary prevention.

AIM: Due to aging populations the incidence of aortic valve stenosis (AVS) is increasing steeply. Since no medical therapy is available but only surgical interventions, it is highly warranted to identify modifiable risk factors for early prevention. The aim of the study was to investigate the associations of cardiovascular risk factors with AVS and to create 10-year absolute risk scores for use in primary prevention. METHODS: In the Copenhagen General Population Study (N=93,979) lifestyle data, biochemical measures, and confounders were assessed at baseline. Risk factors with the strongest association with aortic valve stenosis from Cox regression analyses were included in ten-year risk prediction models. Ten-year absolute risk scores were conducted using the method of Fine-Gray proportional sub-hazards models, accounting for competing events. RESULTS: 1,132 individuals developed AVS during follow-up. Of well-known cardiovascular risk factors, those that associated with AVS included increasing levels of remnant cholesterol, triglycerides, lipoprotein(a), systolic blood pressure, and body mass index, low adherence to Danish dietary guidelines, current smoking, high alcohol consumption, lipid-lowering therapy and diabetes mellitus. Ten-year absolute risk scores increased when compiling the most important risk factors for AVS; age, sex, body mass index, systolic blood pressure, lipoprotein(a), and diabetes. Ten-year absolute risk increased from <1% to 19%. CONCLUSIONS: The presence of cardiovascular risk factors is associated with AVS, supporting that this disease, at least partly, may be modifiable through lifestyle changes. Risk charts combining cardiovascular risk factors have the potential to identify high-risk individuals, offering opportunities for preventive strategies. (Word count 245).

This study investigates the impact of common cardiovascular risk factors on aortic valve stenosis (AVS) and introduces a risk score to predict the likelihood of developing AVS within ten years. We identified strong links between AVS and several risk factors, including lipid traits, high blood pressure, obesity, smoking, increased alcohol intake, low adherence to dietary guidelines, and diabetes. A ten-year risk score combining age, sex, body mass index, blood pressure, the lipid trait lipoprotein(a), and diabetes estimates an individual's future risk of AVS, which can range from 1% to 19%. Such risk scores enable identification of individuals at highest risk, where early prevention is most effective.

Adherence to general national dietary guidelines and risk of psoriasis: results from a general population study of 105 332 individuals.

BACKGROUND: It is unknown if an unhealthy diet can affect the risk of developing psoriasis. OBJECTIVES: To test the hypothesis that individuals with an unhealthy diet have an increased risk of prevalent and incident psoriasis. METHODS: We included 105 332 adults from the Copenhagen General Population Study, who were invited to participate between 2003 and 2015. The response rate was 43%. An unhealthy vs. healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into three groups: low, intermediate and high adherence to general national dietary guidelines; this was based on information from a food frequency questionnaire. Identification of psoriasis was made using International Classification of Diseases codes. RESULTS: Of the 105 332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to nonadherence to general national dietary guidelines in a stepwise manner with an age- and sex-adjusted odds ratio of 1.70 (95% confidence interval 1.26-2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable-adjusted model. Prospective analyses adjusted for age and sex showed a weak association between nonadherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). CONCLUSIONS: Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis.

Vegetarian or vegan diets and blood lipids: a meta-analysis of randomized trials.

AIMS: Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. METHODS AND RESULTS: Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of -0.34 mmol/L (95% confidence interval, -0.44, -0.23; P = 1 × 10-9), -0.30 mmol/L (-0.40, -0.19; P = 4 × 10-8), and -12.92 mg/dL (-22.63, -3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels. CONCLUSION: Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease.

Impact of diet on ten-year absolute cardiovascular risk in a prospective cohort of 94 321 individuals: A tool for implementation of healthy diets.

Background: An unhealthy diet is a major risk factor for cardiovascular disease attributing to the burden of non-communicable diseases. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. We aimed to evaluate the impact of incorporating dietary assessment into ten-year absolute risk charts for atherosclerotic cardiovascular disease (ASCVD). Methods: In the prospective Copenhagen General Population Study including 94 321 individuals, we generated sex-specific ten-year absolute risk scores for ASCVD according to adherence to dietary guidelines, using a short and valid food frequency questionnaire. To account for competing risk, we used the method of Fine-Gray. Findings: Non-adherence to dietary guidelines was associated with an atherogenic lipid and inflammatory profile. Ten-year absolute risk of ASCVD increased with increasing age, increasing systolic blood pressure, and decreasing adherence to dietary guidelines for both sexes. The highest ten-year absolute risk of ASCVD of 38% was observed in men aged 65-69 years who smoked, had very low adherence to dietary guidelines, and a systolic blood pressure between 160 and 179 mmHg. The corresponding value for women was 26%. Risk charts replacing dietary assessment with non-HDL cholesterol yielded similar estimates. Interpretation: Incorporation of a short dietary assessment into ten-year absolute risk charts has the potential to motivate patients to adhere to dietary guideline recommendations. Improved implementation of national dietary guidelines must be a cornerstone for future prevention of cardiovascular disease in both younger and older individuals. Funding: The Lundbeck Foundation (R278-2018-804) and the Danish Heart Foundation.

Plasma high-density lipoprotein cholesterol and risk of dementia: observational and genetic studies.

AIMS: The association of plasma high-density lipoprotein (HDL) cholesterol with risk of dementia is unclear. We, therefore, tested the hypothesis that high levels of plasma HDL cholesterol are associated with increased risk of dementia and whether a potential association is of a causal nature. METHODS AND RESULTS: In two prospective population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study (N = 111 984 individuals), we first tested whether high plasma HDL cholesterol is associated with increased risk of any dementia and its subtypes. These analyses in men and women separately were adjusted multifactorially for other risk factors including apolipoprotein E (APOE) genotype. Second, taking advantage of two-sample Mendelian randomization, we tested whether genetically elevated HDL cholesterol was causally associated with Alzheimer's disease using publicly available consortia data on 643 836 individuals. Observationally, multifactorially adjusted Cox regression restricted cubic spline models showed that both men and women with extreme high HDL cholesterol concentrations had increased risk of any dementia and of Alzheimer's disease. Men in the 96th-99th and 100th vs. the 41st-60th percentiles of HDL cholesterol had multifactorially including APOE genotype adjusted hazard ratios of 1.66 (95% confidence interval 1.30-2.11) and 2.00 (1.35-2.98) for any dementia and 1.59 (1.16-2.20) and 1.87 (1.11-3.16) for Alzheimer's disease. Corresponding estimates for women were 0.94 (0.74-1.18) and 1.45 (1.03-2.05) for any dementia and 0.94 (0.70-1.26) and 1.69 (1.13-2.53) for Alzheimer's disease. Genetically, the two-sample Mendelian randomization odds ratio for Alzheimer's disease per 1 SD increase in HDL cholesterol was 0.92 (0.74-1.10) in the IGAP2019 consortium and 0.98 (0.95-1.00) in the ADSP/IGAP/PGC-ALZ/UKB consortium. Similar estimates were observed in sex stratified analyses. CONCLUSION: High plasma HDL cholesterol was observationally associated with increased risk of any dementia and Alzheimer's disease, suggesting that HDL cholesterol can be used as an easily accessible plasma biomarker for individual risk assessment.

HDL Cholesterol and Non-Cardiovascular Disease: A Narrative Review.

High density lipoprotein (HDL) cholesterol has traditionally been considered the "good cholesterol", and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms.

ABCA7 and risk of dementia and vascular disease in the Danish population.

Objective: ATP-binding-cassette transporter A7(ABCA7) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid-ß in the brain. We tested the hypothesis that a common genetic variant in ABCA7 is associated with dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels in the general population, independent of the common apolipoprotein E(APOE) genotype. Methods: For this purpose, we genotyped a common genetic variant in ABCA7, identified in genome-wide-association-studies of Alzheimer's disease, in 104,258 individuals from the Danish general population, and also meta-analyzed our results with publicly available consortia data. Results: Multifactorially adjusted hazard ratios for Alzheimer's disease were 1.07 (95% confidence interval:0.93-1.23) and 1.72 (1.24-2.40) for GA and AA versus GG genotype. Results were similar after APOE genotype adjustment and when only APOE ɛ33 carriers were studied. Including 178,304 individuals, the meta-analyzed odds ratio for Alzheimer's disease per one allele ABCA7 rs4147929 increase was 1.15 (1.12-1.18). ABCA7 genotype was not convincingly associated with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, or with lipid levels. Including 288,563 individuals, meta-analyzed odds ratios for ischemic heart disease per one allele ABCA7 rs4147929 increase was 1.01 (0.99-1.03). Interpretation: A common genetic variant in ABCA7 was associated with high risk of Alzheimer's disease independent of APOE genotype. The lack of association with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels suggests that ABCA7 is not important for atherosclerosis. Thus, our findings support the suggested role of ABCA7 in Alzheimer's disease pathology and phagocytic clearance of amyloid-ß in the brain.