Elucidation of a Causal Relationship Between Platelet Count and Hypertension: A Bi-Directional Mendelian Randomization Study

Abstract

Hypertension has been reported as a major risk factor for diseases such as cardiovascular disease, and associations between platelet activation and risk for hypertension are well-established. However, the exact nature of causality between them remains unclear. In this study, a bi-directional Mendelian randomization (MR) analysis was conducted on 15,996 healthy Taiwanese individuals aged between 30 and 70 years from the Taiwan Biobank, recorded between 2008 and 2015. The inverse variance weighted (IVW) method was applied to determine the causal relationship between platelet count and hypertension with single nucleotide polymorphisms as instrumental variables (IVs). Furthermore, to check for pleiotropy and validity of the IVs, sensitivity analyses were performed using the MR-Egger, weighted median and simple median methods. This study provided evidence in support of a positive causal effect of platelet count on the risk of hypertension (odds ratio: 1.149, 95% confidence interval: 1.131–1.578, P < 0.05), using the weighted median method. A significant causal effect of platelet count on hypertension was observed using the IVW method. No pleiotropy was observed. The causal effect of hypertension on platelet count was found to be non-significant. Therefore, the findings from this study provide evidence that higher platelet count may have a significant causal effect on the elevated risk of hypertension for the general population of Taiwan.

Platelet Indices and Blood Pressure: A Multivariable Mendelian Randomization Study

“…Increased platelet indices were observed in multiple diseases, such as ischemic heart disease and ischemic strokes [19, 24] [33, 34]. Our ndings of the univariable MR study align with earlier studies on PLT concerning the elevation of BP [22,14]. To the best of our knowledge, no MR study evaluated the effect of the other platelet indices on BP, whereas the association of hypertension with them has been reported in observational studies [14][15][16].…”

“…An alternative approach is the Mendelian randomization (MR) design, which utilizes genetic variants as instrumental variables (IVs) for an exposure to determine the causality of an exposure-outcome association [17,18]. Previous MR research had elucidated the causal relationship between hematological traits and blood pressure as well as other diseases [19][20][21][22]. However, there is only one MR study related to PLT and BP, and PLT on its own is insu cient because platelet indices were correlated [23,24].…”

Components of the Complete Blood Count as a Risk Predictor for Incident Hypertension in a Large Taiwanese Population Follow-up Study

“…26 A bidirectional Mendelian randomization study using cross-sectional data from the TWB found a significant causal effect of high platelet count on an increased risk of HT. 27 In our longitudinal study, we found a negative association between platelet count and incident HT in the univariable analysis, and the relationship became insignificant after multivariable analysis. In the univariate analysis, low platelets were associated with incident HT, probably because platelet counts were lower in males than in females and the platelet count decreases with age; both male sex and age are significant risk factors of incident HT.…”

“…61 However, few studies have investigated the relationship between HT and platelet count. 26, 27 A population-based study in China explored the association between platelet indices and BP using the quadratic inference function method, and showed that platelet count was associated with DBP only in the male participants. 26 A bidirectional Mendelian randomization study using cross-sectional data from the TWB found a significant causal effect of high platelet count on an increased risk of HT.…”

“…Such results were also found in a previous study using the same TWB database. 27 In addition, a high platelet count is associated with incident HT exclusively in men, indicating that the role of platelets in the development of incident HT differs by sex. This implied that platelet count might be associated with the risk of HT, but the association was weak and easily confounded by still significantly associated with incident HT in the multivariable analysis.…”