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The association between thyroid stimulating hormone (TSH) and cardiovascular disease has mainly been determined using clinical categories of disease. We tested the hypothesis that TSH on a continuous scale is associated with risk of atrial fibrillation (AF), myocardial infarction (MI), stroke, heart failure (HF), aortic valve stenosis (AVS), and major adverse cardiovascular events (MACE) and whether these associations are likely to be causal. We first tested whether plasma TSH on a continuous scale was observationally associated with incident cardiovascular events in a prospective cohort study of 105,224 individuals from the Copenhagen General Population Study followed for a median 7 years. Next, we tested whether a genetic risk score weighted on TSH was associated with cardiovascular endpoints. Finally, using Mendelian randomization, we tested whether the observed associations were likely to be causal. Using restricted cubic splines, lower concentrations of TSH relative to the population median (=1.53 mIU/L) were associated with higher risk of AF, MI, stroke, HF, AVS, and MACE. Comparing individuals with TSH ≤5th percentile (≤0.54 mIU/L) versus >50th percentile (>1.53 mIU/L), hazard ratios (HRs) ranged from 1.12 (1.00–1.26) for stroke to 1.27 (1.11–1.46) for HF. Genetic risk estimates per standard deviation decrease in TSH were 1.28 (1.08–1.52) for AF, 1.35 (1.06–1.71) for MI, 1.06 (0.89–1.26) for stroke, 1.19 (0.94–1.52) for HF, 1.53 (1.03–2.26) for AVS, and 1.09 (0.97–1.23) for MACE. In 105,224 individuals from the general population low plasma TSH was observationally and genetically associated with increased risk of AF, MI, and AVS suggesting that these observations may reflect causal pathways. [Display omitted] • We tested the hypothesis that TSH was associated with cardiovascular disease (CVD). • 105,224 individuals from the general population were followed for a median of 7 years. • Observationally, TSH below the median was associated with increased risk of CVD. • Genetically, Mendelian randomization suggested possible causal associations. [ABSTRACT FROM AUTHOR]

Elevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality. The Copenhagen General Population Study randomly recruited white Danish individuals aged 20–100 years in 2003–2015 and followed them for a median 9.5 years. ASCVD was cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization. In 103,221 individuals, we observed 2,454 (2.4%) myocardial infarctions, 5,437 (5.3%) ASCVD events, and 10,521 (10.2%) deaths. The hazard ratios increased with each of stepwise higher remnant cholesterol and stepwise higher C-reactive protein. In individuals with the highest tertile of both remnant cholesterol and C-reactive protein compared to individuals with the lowest tertile of both, the multivariable adjusted hazard ratios were 2.2 (95%CI:1.9–2.7) for myocardial infarction, 1.9 (1.7–2.2) for ASCVD, and 1.4 (1.3–1.5) for all-cause mortality. Corresponding values for only the highest tertile of remnant cholesterol were 1.6 (1.5–1.8), 1.4 (1.3–1.5), and 1.1 (1.0–1.1), and those for only the highest tertile of C-reactive protein were 1.7 (1.5–1.8), 1.6 (1.5–1.7), and 1.3 (1.3–1.4), respectively. There was no statistical evidence for interaction between elevated remnant cholesterol and elevated C-reactive protein on risk of myocardial infarction (p = 0.10), ASCVD (p = 0.40), or all-cause mortality (p = 0.74). Dual elevated remnant cholesterol and C-reactive protein confers the highest risk of myocardial infarction, ASCVD, and all-cause mortality, that is, compared to either of these two factors individually. [Display omitted] • Dual elevated remnant-C and CRP was associated with the highest risk of ASCVD. • ASCVD risk is particularly relevant if remnant-C is ≥ 0.8 mmol/L and CRP ≥1.5 mg/L. • ASCVD risk was double in the highest tertile of both compared to the lowest. [ABSTRACT FROM AUTHOR]

In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical development. This advice counters the attitude: "Why should I measure Lp(a) if I can't lower it?". Subsequent to publication, questions have arisen relating to how the recommendations of this statement impact everyday clinical practice and ASCVD management. This review addresses 30 of the most frequently asked questions about Lp(a) epidemiology, its contribution to cardiovascular risk, Lp(a) measurement, risk factor management and existing therapeutic options. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and aims We estimated the extent of undertreatment and overtreatment with cholesterol-lowering therapy according to European guidelines in individuals in the Danish general population without ischemic cardiovascular disease and diabetes. Methods We examined 92,348 such individuals aged 35–100 years recruited from 2004 through 2014 in the Copenhagen General Population Study. Each individual was assigned their 10-year risk of fatal cardiovascular disease according to the European SCORE chart based on age, sex, smoking, total cholesterol, and systolic blood pressure. European guidelines recommend cholesterol-lowering therapy definitely at ≥10% risk and LDL cholesterol ≥1.8 mmol/L, definitely at 5–9% risk and LDL cholesterol ≥2.5 mmol/L, possibly at 1–4% risk and LDL cholesterol ≥3 mmol/L, but not at <1% risk. Results 3858 individuals had ≥10% risk, 16,255 had 5–9% risk, 49,131 had 1–4% risk, and 23,104 had <1% 10-year risk of fatal cardiovascular disease. In these groups, 81%, 86%, 93%, and 99% did not receive cholesterol-lowering therapy. Definite undertreatment and overtreatment according to guidelines were found in 19% and 0.2% or in 187,660 and 1570 per million 35–100 year olds without ischemic cardiovascular disease and diabetes. If definite and possible undertreatment and overtreatment were combined, the corresponding numbers were 52% and 3% or 519,416 and 29,194 per million. Conclusions In the Danish general population, ∼190,000 per million 35–100 year olds without ischemic cardiovascular disease and diabetes are not treated to LDL cholesterol goals according to European guidelines. Conversely, ∼1600 per million received cholesterol-lowering therapy without endorsement in European guidelines. [ABSTRACT FROM AUTHOR]

Children with a growth trajectory of overweight have higher levels of cardiovascular disease (CVD) risk factors than children with a normal-weight trajectory. However, less is known about how trajectories of body mass index (BMI) across the rest of the BMI spectrum relate to CVD risk factors and whether adult BMI affects these associations. Our aim was to examine associations between childhood BMI trajectories and adult CVD risk factors. We included 2466 individuals with childhood weights and heights (ages 6–14) from the Copenhagen School Health Records Register and adult CVD risk factors (ages 20–81) from the Copenhagen City Heart Study. Associations between childhood BMI trajectories identified by latent class modelling and CVD risk factors were examined using generalized linear regression analyses with and without adjustment for adult BMI. Normal-weight and overweight were defined by growth references from the Centers for Disease Control and Prevention. We identified four childhood trajectories within the normal-weight spectrum and one trajectory of overweight. Compared to the trajectory with the lowest BMI level, several higher BMI trajectories were associated with worse circumference, HDL and glucose homeostasis in adulthood. The highest trajectory was additionally associated with higher total cholesterol and triglycerides. When adjusting for adult BMI, the higher BMI trajectories had lower waist circumference, blood pressure and triglycerides. Trajectories of BMI within the normal-weight range and in the overweight range are associated with a worse CVD risk profile than in the lowest BMI trajectory, and these associations are modifiable by growth after childhood. Image 1 • Five different trajectories of body mass index from ages 6-14 were identified in a population of 2466 Danish children. • The trajectory above overweight cutoffs was associated with the worst cardiovascular disease risk factor profile. • Even trajectories below overweight cutoffs had worse cardiovascular disease risk factor profiles than the lowest trajectory. • These associations appeared to be modifiable by body mass index development after age 14. [ABSTRACT FROM AUTHOR]