A1 Refereed original research article in a scientific journal
Unsupervised hierarchical clustering identifies a metabolically challenged subgroup of hypertensive individuals
Authors: Felix C. Vaura, Veikko V. Salomaa, Ilkka M. Kantola, Risto Kaaja, Leo Lahti, Teemu J. Niiranen
Publisher: WILEY
Publication year: 2020
Journal: Journal of Clinical Hypertension
Journal name in source: JOURNAL OF CLINICAL HYPERTENSION
Journal acronym: J CLIN HYPERTENS
Volume: 22
Issue: 9
First page : 1546
Last page: 1553
Number of pages: 8
ISSN: 1524-6175
eISSN: 1751-7176
DOI: https://doi.org/10.1111/jch.13984
Self-archived copy’s web address: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029868
Abstract
The current classification of hypertension does not reflect the heterogeneity in characteristics or cardiovascular outcomes of hypertensive individuals. Our objective was to identify distinct phenotypes of hypertensive individuals with potentially different cardiovascular risk profiles using data-driven cluster analysis. We performed clustering, a procedure that identifies groups with similar characteristics, in 3726 individuals (mean age 59.4 years, 49% women) with grade 2 hypertension (blood pressure >= 160/100 mmHg or antihypertensive medication) selected from FINRISK 1997, 2002, and 2007 cohorts. We computed clusters based on eight factors associated with hypertension: mean arterial pressure, pulse pressure, non-high-density lipoprotein cholesterol, blood glucose, BMI, C-reactive protein, estimated glomerular filtration rate, and alcohol. After that, we used Cox regression models adjusted for age and sex to assess the relative risk of cardiovascular disease (CVD) outcomes between the clusters and a reference group of 11 020 individuals. We observed two comparable clusters in both men and women. The Metabolically Challenged (MC) cluster was characterized by high blood glucose (Z-score 4.4 +/- 1.1 vs 0.2 +/- 0.8, men; 3.5 +/- 1.1 vs 0.0 +/- 0.6, women) and elevated BMI (30.4 +/- 4.1 vs 28.9 +/- 4.3, men; 32.7 +/- 4.9 vs 29.3 +/- 5.5, women). Over a 10-year follow-up (1034 CVD events), MC had 1.6-fold (95% CI 1.1-2.4) CVD risk compared to non-MC and 2.5-fold (95% CI 1.7-3.7) CVD risk compared to the reference group (P <= .009 for both). Using unsupervised hierarchical clustering, we found two phenotypically distinct hypertension subgroups with different risks of CVD complications. This substratification could be used to design studies that explore the differential effects of antihypertensive therapies among subgroups of hypertensive individuals.
The current classification of hypertension does not reflect the heterogeneity in characteristics or cardiovascular outcomes of hypertensive individuals. Our objective was to identify distinct phenotypes of hypertensive individuals with potentially different cardiovascular risk profiles using data-driven cluster analysis. We performed clustering, a procedure that identifies groups with similar characteristics, in 3726 individuals (mean age 59.4 years, 49% women) with grade 2 hypertension (blood pressure >= 160/100 mmHg or antihypertensive medication) selected from FINRISK 1997, 2002, and 2007 cohorts. We computed clusters based on eight factors associated with hypertension: mean arterial pressure, pulse pressure, non-high-density lipoprotein cholesterol, blood glucose, BMI, C-reactive protein, estimated glomerular filtration rate, and alcohol. After that, we used Cox regression models adjusted for age and sex to assess the relative risk of cardiovascular disease (CVD) outcomes between the clusters and a reference group of 11 020 individuals. We observed two comparable clusters in both men and women. The Metabolically Challenged (MC) cluster was characterized by high blood glucose (Z-score 4.4 +/- 1.1 vs 0.2 +/- 0.8, men; 3.5 +/- 1.1 vs 0.0 +/- 0.6, women) and elevated BMI (30.4 +/- 4.1 vs 28.9 +/- 4.3, men; 32.7 +/- 4.9 vs 29.3 +/- 5.5, women). Over a 10-year follow-up (1034 CVD events), MC had 1.6-fold (95% CI 1.1-2.4) CVD risk compared to non-MC and 2.5-fold (95% CI 1.7-3.7) CVD risk compared to the reference group (P <= .009 for both). Using unsupervised hierarchical clustering, we found two phenotypically distinct hypertension subgroups with different risks of CVD complications. This substratification could be used to design studies that explore the differential effects of antihypertensive therapies among subgroups of hypertensive individuals.
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