Obesity as a Causal Risk Factor for Aortic Valve Stenosis

Kaltoft, Mikkel; Langsted, Anne; Nordestgaard, Børge G.

doi:10.1016/j.jacc.2019.10.050

Cited by 59 publications

(50 citation statements)

References 39 publications

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“…For several outcomes, two or more studies were published based on outcome data from the same source population (e.g., same consortium or UK Biobank). One two-sample MR study did not indicate the statistical method used for the primary analysis [ 14 ], and eight studies did report results of sensitivity analyses based on robust MR methods (e.g., weighted median and MR-Egger regression) [ 9 , 11 , 17 , 24 , 25 , 35 , 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies

Larsson

Burgess

2021

BMC Med

120

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Background Obesity is a worldwide epidemic that has been associated with a plurality of diseases in observational studies. The aim of this study was to summarize the evidence from Mendelian randomization (MR) studies of the association between body mass index (BMI) and chronic diseases. Methods PubMed and Embase were searched for MR studies on adult BMI in relation to major chronic diseases, including diabetes mellitus; diseases of the circulatory, respiratory, digestive, musculoskeletal, and nervous systems; and neoplasms. A meta-analysis was performed for each disease by using results from published MR studies and corresponding de novo analyses based on summary-level genetic data from the FinnGen consortium (n = 218,792 individuals). Results In a meta-analysis of results from published MR studies and de novo analyses of the FinnGen consortium, genetically predicted higher BMI was associated with increased risk of type 2 diabetes mellitus, 14 circulatory disease outcomes, asthma, chronic obstructive pulmonary disease, five digestive system diseases, three musculoskeletal system diseases, and multiple sclerosis as well as cancers of the digestive system (six cancer sites), uterus, kidney, and bladder. In contrast, genetically predicted higher adult BMI was associated with a decreased risk of Dupuytren’s disease, osteoporosis, and breast, prostate, and non-melanoma cancer, and not associated with Alzheimer’s disease, amyotrophic lateral sclerosis, or Parkinson’s disease. Conclusions The totality of the evidence from MR studies supports a causal role of excess adiposity in a plurality of chronic diseases. Hence, continued efforts to reduce the prevalence of overweight and obesity are a major public health goal.

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Section: Resultsmentioning

confidence: 99%

Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies

Larsson

Burgess

2021

BMC Med

120

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“…Yet, our results provide some data and help clarify this issue, which has been controversial. Some studies showed a positive association between AS and obesity, including a Swedish study using patient registries [ 24 ], a large case–control study with older patients with severe calcified AS [ 4 ], and a recent Danish study [ 5 ]. Three more studies showed a positive correlation between BMI and aortic valve calcification [ 8 , 25 , 26 ], whereas three others did not show such a correlation.…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiological changes leading to aortic valve sclerosis and AS result from the synergy of the mechanical forces and the changes in the tissular environment sharing similarities with changes encountered in ischemic heart disease [ 3 ]. Studies have shown an association between AS and obesity [ 4 , 5 ], hypercholesterolemia [ 6 – 9 ] or hypertension [ 6 , 7 , 10 , 11 ], with increasing evidence that atherosclerotic risk factors might also affect the development of aortic valve sclerosis and its progression to AS. However, another question arises as to whether the relationships mentioned above between AS and risk factors persist over the life course, considering that several of these factors are prone to change over time.…”

Section: Introductionmentioning

confidence: 99%

Cumulative incidence and predictors of acquired aortic stenosis in a large population of men followed for up to 43 years

Kontogeorgos

Thunström

Lappas

et al. 2022

BMC Cardiovasc Disord

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Background Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. Methods We included a random sample of men (n = 9998) born 1915–1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25–43, 30–43 and 35–43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. Results The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20–22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25–27.5 kg/m2, 27.5–30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12–3.55), 2.98 (95% CI 1.65–5.40) and 3.55 (95% CI 1.84–6.87), respectively. Conclusions The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

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“…This would also explain why patients with obesity, who are known to have a higher stroke volume, display accelerated progression of AS. 10 11 …”

Section: Discussionmentioning

confidence: 99%

Mild aortic valve disease and the diastolic pressure–volume relationship in heart failure with preserved ejection fraction

et al. 2021

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ObjectiveMild aortic valve stenosis (AS) and aortic valve (AV) sclerosis are associated with diastolic dysfunction and increased mortality in the general population. This study specifically investigated the impact of mild AV disease in heart failure with preserved ejection fraction (HFpEF).MethodsConsecutive patients hospitalised with HFpEF (n=370) underwent assessment of cardiac structure and function and long-term clinical follow-up.ResultsIn the study cohort, 111 had mild AS (30%), 104 AV sclerosis (28%) and 155 a non-calcified AV (42%). Mild-to-moderate AV regurgitation (AR) was present in 64 (17%). Compared with patients with a normal AV, those with AV disease were older, with worse renal function and more atrial fibrillation. E/e′ increased from non-calcified AV to AV sclerosis to mild AS (13.8 (10.8–16.8) vs 15.0 (10.9–20.0) vs 18.0 (12.7–23.3), respectively; p<0.001)). Left ventricular diastolic pressure–volume relationships were shifted leftwards in patients with AS and AV sclerosis, but not influenced by AR. The left ventricular end-diastolic volume normalised at 20 mm Hg was 117±34 mL, 106±30 mL and 112±30 mL in non-calcified AV, AV sclerosis and mild AS, respectively (p=0.023), while 112±32 mL in mild-to-moderate AR. Over 30 months (IQR, 8–61 months), 247 patients died (67%). The presence of mild AV disease was associated with increased mortality, but this was no longer significant after adjusting for age and sex.ConclusionsLow-grade AV disease is common among patients hospitalised for HFpEF and is associated with older age, atrial arrhythmia, renal dysfunction, higher left heart filling pressures and increased left ventricular chamber stiffness.

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Obesity as a Causal Risk Factor for Aortic Valve Stenosis

Cited by 59 publications

References 39 publications

Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies

Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies

Cumulative incidence and predictors of acquired aortic stenosis in a large population of men followed for up to 43 years

Mild aortic valve disease and the diastolic pressure–volume relationship in heart failure with preserved ejection fraction

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