Dataset Information

No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis.

ABSTRACT:

Background

Reduced heart rate (HR) increase (HRI), recovery (HRR), and higher resting HR are associated with cardiovascular (CV) disease, but causal inferences have not been deduced. We investigated causal effects of HRI, HRR, and resting HR on CV risk, all-cause mortality (ACM), atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke (IS) using Mendelian Randomization.

Methods

11 variants for HRI, 11 for HRR, and two sets of 46 and 414 variants for resting HR were obtained from four genome-wide association studies (GWASs) on UK Biobank. We performed a lookup on GWASs for CV risk and ACM in UK Biobank (N = 375,367, 5.4% cases and N = 393,165, 4.4% cases, respectively). For CAD, AF, and IS, we used publicly available summary statistics. We used a random-effects inverse-variance weighted (IVW) method and sensitivity analyses to estimate causality.

Results

IVW showed a nominally significant effect of HRI on CV events (odds ratio [OR] = 1.0012, P = 4.11 × 10^-2) and on CAD and AF. Regarding HRR, IVW was not significant for any outcome. The IVW method indicated statistically significant associations of resting HR with AF (OR = 0.9825, P = 9.8 × 10^-6), supported by all sensitivity analyses, and a nominally significant association with IS (OR = 0.9926, P = 9.82 × 10^-3).

Conclusion

Our findings suggest no strong evidence of an association between HRI and HRR and any outcome and confirm prior work reporting a highly significant effect of resting HR on AF. Future research is required to explore HRI and HRR associations further using more powerful predictors, when available.

SUBMITTER: Mensah-Kane J

PROVIDER: S-EPMC7931909 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis.

Mensah-Kane Josephine J Schmidt Amand F AF Hingorani Aroon D AD Finan Chris C Chen Yutang Y van Duijvenboden Stefan S Orini Michele M Lambiase Pier D PD Tinker Andrew A Marouli Eirini E Munroe Patricia B PB Ramírez Julia J

Frontiers in genetics 20210218

<h4>Background</h4>Reduced heart rate (HR) increase (HRI), recovery (HRR), and higher resting HR are associated with cardiovascular (CV) disease, but causal inferences have not been deduced. We investigated causal effects of HRI, HRR, and resting HR on CV risk, all-cause mortality (ACM), atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke (IS) using Mendelian Randomization.<h4>Methods</h4>11 variants for HRI, 11 for HRR, and two sets of 46 and 414 variants for resting HR ...[more]

PMID: 33679875

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Project description:BACKGROUND: Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. METHODS: Three population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. RESULTS: Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. CONCLUSION: Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Dataset Information

No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis.

Background

Methods

Results

Conclusion

Publications

No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis.

Similar Datasets

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