Accurate blood pressure (BP) measurement is essential in epidemiological studies, screening programmes, and research studies as well as in clinical practice for the early detection and prevention of high BP-related risks such as coronary heart disease, stroke, and kidney failure. Posture of the participant plays a vital role in accurate measurement of BP. Guidelines on measurement of BP contain recommendations on the position of the back of the participants by advising that they should sit with supported back to avoid spuriously high readings. In this work, principal component analysis (PCA) is fused with forward stepwise regression (SWR), artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS), and the least squares support vector machine (LS-SVM) model for the prediction of BP reactivity to an unsupported back in normotensive and hypertensive participants. PCA is used to remove multi-collinearity among anthropometric predictor variables and to select a subset of components, termed ‘principal components’ (PCs), from the original dataset. The selected PCs are fed into the proposed models for modeling and testing. The evaluation of the performance of the constructed models, using appropriate statistical indices, shows clearly that a PCA-based LS-SVM (PCA-LS-SVM) model is a promising approach for the prediction of BP reactivity in comparison to others. This assessment demonstrates the importance and advantages posed by hybrid models for the prediction of variables in biomedical research studies.