Assessing gaps in cholesterol treatment guidelines for primary prevention of cardiovascular disease based on available randomised clinical trial evidence: The Rotterdam Study.

Background The purpose of this study was to determine how American College of Cardiology/American Heart Association (ACC/AHA) 2013 and European Society of Cardiology 2016 guidelines for the primary prevention of atherosclerotic cardiovascular disease (CVD) compare in reflecting the totality of accrued randomised clinical trial evidence for statin treatment at population level. Methods From 1997-2008, 7279 participants aged 45-75 years, free of atherosclerotic cardiovascular disease, from the population-based Rotterdam Study were included. For each participant, we compared eligibility for each one of 11 randomised clinical trials on statin use in primary prevention of CVD, with recommendations on lipid-lowering therapy from the ACC/AHA and European Society of Cardiology (ESC) guidelines.

High Circulating Free Thyroxine Levels May Increase the Risk of Frailty: The Rotterdam Study.

Context: Thyroid hormones affect metabolism in various tissues, organs, and systems. However, the overall impact of thyroid function on an individual's vulnerability to adverse outcomes remains unclear.

Objective: To investigate the cross-sectional and prospective association of thyroid function with the frailty index, a well-established measure of overall health.

Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women.

Objective: To better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data.

Methods: Early menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study.

Associations of Endogenous Estradiol and Testosterone Levels With Plaque Composition and Risk of Stroke in Subjects With Carotid Atherosclerosis.

Rationale: Sex steroids may play a role in plaque composition and in stroke incidence.

Objectives: To study the associations of endogenous estradiol and testosterone with carotid plaque composition in elderly men and postmenopausal women with carotid atherosclerosis, as well as with risk of stroke in this population.

Methods And Results: Data of 1023 postmenopausal women and 1124 men (≥45 years) with carotid atherosclerosis, from prospective population-based RS (Rotterdam Study), were available.

Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study.

Rationale: Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear.

Objective: To investigate the association of thyroid function with atherosclerosis throughout its spectrum; that is, subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events, and ASCV mortality.

Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation.

Background And Aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels.

Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease: The Rotterdam Study.

Importance: Variations in thyroid function within reference ranges are associated with an increased risk of cardiovascular disease (CVD) and mortality. However, the impact of thyroid function on life expectancy (LE) and the number of years lived with and without CVD remains unknown.

Objective: To investigate the association of thyroid function with total LE and LE with and without CVD among euthyroid individuals.

Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults: An Analysis of Pooled Population-Based Studies.

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults.

Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models.

Design, Setting, And Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study.

Aims/hypothesis: In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.

Methods: We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40-44 years; normal, 45-55 years; and late menopause, >55 years [reference]).

Subclinical vascular disease and the risk of parkinsonism: The Rotterdam Study.

Background: Parkinsonism is a common neurodegenerative syndrome in middle-aged and elderly persons. The etiology is multifactorial with a possible vascular contribution, but this has not been comprehensively studied.

Objective: To determine whether selected markers of subclinical vascular pathology are associated with the risk of all-cause parkinsonism in the general population.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred.

Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study.

Unlabelled: The immune response involved in each phase of type 2 diabetes (T2D) development might be different. We aimed to identify novel inflammatory markers that predict progression from normoglycemia to pre-diabetes, incident T2D and insulin therapy. We used plasma levels of 26 inflammatory markers in 971 subjects from the Rotterdam Study.

Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis.

It remains unclear whether endogenous sex hormones (ESH) are associated with risk of type 2 diabetes (T2D) in women. Data of 3,117 postmenopausal women participants of the Rotterdam Study were analyzed to examine whether ESH and sex hormone-binding globulin (SHBG) were associated with the risk of incident T2D. Additionally, we performed a systematic review and meta-analysis of studies assessing the prospective association of ESH and SHBG with T2D in women.

Development of a Healthy Aging Score in the Population-Based Rotterdam Study: Evaluating Age and Sex Differences.

Objectives: To develop a healthy aging score (HAS), to assess age and sex differences in HAS, and to evaluate the association of the HAS with survival.

Design: Prospective population-based cohort.

Setting: Inhabitants of Ommoord, Rotterdam, The Netherlands.

Serum Levels of Apolipoproteins and Incident Type 2 Diabetes: A Prospective Cohort Study.

Objective: We aimed to investigate the role of serum levels of various apolipoproteins on the risk for type 2 diabetes (T2D).

Research Design And Methods: We used data from 971 individuals from the prospective population-based Rotterdam Study. We studied the association of HDL cholesterol (HDL-C), apoA1, apoCIII, apoD, and apoE as well as the ratios of apolipoproteins with apoA1 with the risk of T2D.

Fertile lifespan characteristics and all-cause and cause-specific mortality among postmenopausal women: the Rotterdam Study.

Objective: To characterize the relation between established and previously unexplored characteristics of the fertile life with all-cause and cause-specific mortality.

Design: Prospective cohort study.

Setting: Not applicable.

Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis.

Background: The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.

Methods And Results: We studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology).

Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.

Importance: The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear.

Objective: To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.

Design, Setting, And Participants: Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.

Aortic Valve Calcification and Risk of Stroke: The Rotterdam Study.

Background And Purpose: It remains uncertain whether aortic valve calcification (AVC) is a risk factor for stroke.

Methods: From the population-based Rotterdam Study, 2471 participants (mean age: 69.6 years; 51.

Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.

Aims/hypothesis: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes.

Methods: We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study.

Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis.

Importance: As many as 10% of women experience natural menopause by the age of 45 years. If confirmed, an increased risk of cardiovascular disease (CVD) and all-cause mortality associated with premature and early-onset menopause could be an important factor affecting risk of disease and mortality among middle-aged and older women.

Objective: To systematically review and meta-analyze studies evaluating the effect of age at onset of menopause and duration since onset of menopause on intermediate CVD end points, CVD outcomes, and all-cause mortality.