Abstract
The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross‐sectional analysis of 3857 older, community‐dwelling men. “Consensus OH” was defined as a sitting‐to‐standing decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05‐1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35‐3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04‐2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31‐3.44), high‐sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07‐2.65) and N‐terminal pro‐brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14‐4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.
Highlights
Orthostatic hypotension (OH) is an age-dependent physical sign[1] that is present in almost one in five community-dwelling adults who are aged 60 years or above.[2]
A small, cross-sectional analysis has shown OH to be associated with the inflammatory biomarkers midkine, immunoglobulin-like transcript 3, and regenerating islet-derived protein 4.11 Another small, cross-sectional analysis has shown OH to be associated with increased concentration of von Willebrand factor (VWF),[12] a glycoprotein involved in hemostasis that is implicated in both endothelial dysfunction and activation.[13]
To further understand how OH increases risk of cardiovascular disease in older adults, in whom the burden of OH is greatest, we examined the association between OH and circulating cardiovascular risk markers implicated in metabolic risk, inflammation, endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress
Summary
Orthostatic hypotension (OH) is an age-dependent physical sign[1] that is present in almost one in five community-dwelling adults who are aged 60 years or above.[2] Mounting observational data have emerged over the last two decades suggesting OH increases risk of all-cause mortality,[3,4] and that it may be an independent risk factor for cardiovascular disease, including stroke, heart failure, atrial fibrillation, and myocardial infarction.[4,5,6,7,8] OH has been associated with subclinical atherosclerotic vascular disease[9] and structural and functional cardiac changes, including left ventricular hypertrophy and diastolic dysfunction.[10] there is no consensus regarding the underlying mechanisms which explain how OH results in these pathological changes and increases cardiovascular risk. These findings implicate inflammation and endothelial dysfunction—both important contributors to atherosclerosis,[14,15] a major cause of cardiovascular disease—as well as myocardial injury and cardiac stress as mechanisms that may explain the association between OH and increased risk of cardiovascular disease
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