Predictive value of traditional risk factors for cardiovascular disease in older people: A systematic review.

With increasing age, associations between traditional risk factors (TRFs) and cardiovascular disease (CVD) shift. It is unknown which mid-life risk factors remain relevant predictors for CVD in older people. We systematically searched PubMed and EMBASE on August 16th 2019 for studies assessing predictive ability of >1 of fourteen TRFs for fatal and non-fatal CVD, in the general population aged 60+. We included 12 studies, comprising 11 unique cohorts. TRF were evaluated in 2 to 11 cohorts, and retained in 0-70% of the cohorts: age (70%), diabetes (64%), male sex (57%), systolic blood pressure (SBP) (50%), smoking (36%), high-density lipoprotein cholesterol (HDL) (33%), left ventricular hypertrophy (LVH) (33%), total cholesterol (22%), diastolic blood pressure (20%), antihypertensive medication use (AHM) (20%), body mass index (BMI) (0%), hypertension (0%), low-density lipoprotein cholesterol (0%). In studies with low to moderate risk of bias, systolic blood pressure (SBP) (80%), smoking (80%) and HDL cholesterol (60%) were more often retained. Model performance was moderate with C-statistics ranging from 0.61 to 0.77. Compared to middle-aged adults, in people aged 60+ different risk factors predict CVD and current prediction models perform only moderate at best. According to most studies, age, sex and diabetes seem valuable predictors of CVD in old-age. SBP, HDL cholesterol and smoking may also have predictive value. Other blood pressure and cholesterol related variables, BMI, and LVH seem of very limited or no additional value. Without competing risk analysis, predictors are overestimated.

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over.

BACKGROUND: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. METHODS: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. DISCUSSION: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date. TRIAL REGISTRATION: Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).