Key result
The glucose-related hypertension phenotype was associated with a higher risk of all-cause mortality compared to early-onset hypertension.
Why the study?
Current hypertension classifications based solely on systolic and diastolic blood pressure fail to capture biological heterogeneity linked to variation in mortality outcomes.
Do data-driven clinical phenotypes of primary hypertension predict mortality risk in adults with newly diagnosed or undiagnosed hypertension?
Cross-Sectional (n=4,084)
Yes
Do data-driven clinical phenotypes of primary hypertension predict mortality risk in adults with newly diagnosed or undiagnosed hypertension?
A data-driven cluster analysis identified four distinct hypertension phenotypes, with glucose-related hypertension carrying the highest risk of all-cause and cardiovascular mortality.
Answers are grounded in this paper and cite their sources.
Glucose-related hypertension phenotype linked to highest mortality; hypothesis-generating for data-driven risk stratification pending prospective validation.
Background: Hypertension is a leading, yet modifiable, cause of mortality worldwide. While current treatment guidelines apply uniformly, variation in outcomes suggests unrecognized biological heterogeneity. Existing classifications based solely on systolic and diastolic blood pressure fail to capture this complexity. We identified data-driven clinical phenotypes of primary hypertension and examined their associations with mortality. Methods: Pooled analysis of 10 cross-sectional surveys (NHANES 1999-2020). Data from 4084 adults (≥ 30 years) with newly diagnosed or undiagnosed hypertension were collected. Hypertension was defined by self-report (in the last 2 years) or those with undiagnosed high systolic or diastolic blood pressure (≥ 140/90 mmHg). Predictors: age, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL-c), hemoglobin A1c, and estimated glomerular filtration rate (eGFR). We used these variables because they are readily available in primary care settings, enabling clinical translation of these findings. We used k-means clustering of eight variables to identify phenotypes. Using mortality data linked to the National Death Index, we estimated the risk of all-cause and cardiovascular mortality. Results: Four phenotypes: Early-onset hypertension (EOH), late-onset hypertension (LOH), glucose-related hypertension (GRH), and lipid-related hypertension (LRH). EOH (37.3%) consisted of younger adults with high BMI and diastolic blood pressure, and low systolic blood pressure and HDL-c. LOH (32.6%) consisted of older adults with low diastolic blood pressure, total cholesterol, and eGFR. GRH (4.5%) consisted of adults with high BMI and HbA1c. LRH (25.6%) consisted of adults with high systolic blood pressure, total cholesterol, and HDL-c and low BMI and HbA1c. Compared to EOH, mortality was the highest in GRH (all-cause: 3.45 [1.80-6.61]; cardiovascular: 5.40 [2.18-13.37]), yet not significant for LOH (1.18 [0.74-1.87]; 1.04 [0.49-2.21]) and LRH (1.01 [0.62-1.63]; 0.93 [0.46-1.87]). Conclusions: This data-driven cluster analysis identified four phenotypes with different mortality risks in people with newly diagnosed hypertension.
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A 2025 study conducted a cross-sectional in Hypertension (n=4,084). Glucose-related hypertension (GRH) phenotype vs. Early-onset hypertension (EOH) phenotype was evaluated on All-cause mortality (HR 3.45, 95% CI 1.80-6.61). The glucose-related hypertension phenotype was associated with a higher risk of all-cause mortality compared to early-onset hypertension.
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