What does this research mean for the field?

Higher blood pressure significantly amplifies the 10-year risk of major adverse cardiovascular events in underweight adults, with the risk increasing markedly as blood pressure categories rise. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate whether the 10-year risk of major adverse cardiovascular events associated with body mass index differs across categories of blood pressure.

September 1, 2026Hypertension ResearchOpen Access

Underweight with stage 2/3 hypertension linked to ~400% higher MACE risk vs normal weight and BP.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertension and Underweight (n=6262298). Intervention: Underweight combined with stage 2/3 hypertension vs. Normal weight with normal blood pressure. Primary outcome: Major adverse cardiovascular events (MACEs) within 10 years (HR 5.01, 95% CI 4.23-5.93, p=<0.01).

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Why the study?

Does body mass index modify the risk of major adverse cardiovascular events across blood pressure categories in adults without prior cardiovascular disease?

Population

6,262,298 adults without prior cardiovascular disease, chronic renal failure, dialysis, or antihypertensive…

Comparison

Underweight across different blood pressure… vs Normal weight with normal blood pressure

Design

Cohort

Follow-up

median 1,183 days

Key result

Underweight combined with stage 2/3 hypertension significantly increased the risk of major adverse cardiovascular events (HR 5.01) compared to normal weight with normal blood pressure.

Authors

TKTakahisa Kawano TSTomohisa Seki HAHiroaki Araie

Discussion

Member takes

Overview

Underweight adults with stage 2/3 hypertension warrant careful risk assessment; extends obesity-focused data but leaves open causal mechanisms and targeted interventions.

Key Points

To evaluate whether the 10-year risk of major adverse cardiovascular events associated with body mass index differs across categories of blood pressure.
Analyzed nationwide medical claims data from Japan (2005–2023) involving 6,262,298 adults without prior cardiovascular disease, chronic renal failure, dialysis, or baseline antihypertensive use.
Categorized blood pressure into five tiers and body mass index into underweight, normal weight, overweight, and obesity.
Used multivariable Cox proportional hazards models to assess 10-year risk of major adverse cardiovascular events across combined categories over a median follow-up of 1,183 days.
A total of 34,034 major adverse cardiovascular events occurred over the follow-up period.
Underweight status was associated with a blood pressure-dependent increase in risk, with hazard ratios escalating from 1.14 (95% CI, 1.07–1.22) in normal blood pressure to 5.01 (95% CI, 4.23–5.93) in stage 2/3 hypertension relative to normal weight with normal blood pressure.
A statistically significant interaction occurred between body mass index and blood pressure categories in predicting major cardiovascular outcomes.

Study Design

Type

Cohort (n=6,262,298)

Multicenter

Yes

Structured PICO

Does body mass index modify the risk of major adverse cardiovascular events across blood pressure categories in adults without prior cardiovascular disease?

Population

6,262,298 Japanese adults aged 18-65 years without prior cardiovascular disease or antihypertensive medication use, followed for a median of 1,183 days to assess the joint association of blood pressure and BMI categories with cardiovascular risk.

Exposure

Underweight (<18.5 kg/m²) across different blood pressure categories (normal, high-normal, elevated, stage 1 hypertension, stage 2/3 hypertension)

Comparator

Normal weight (18.5–24.9 kg/m²) with normal blood pressure (<120 and <80 mmHg)

Outcome

Major adverse cardiovascular events within 10 yearscomposite

Main Result

Hazard Ratio: 5.01 (95% CI 4.23–5.93)

Absolute Event Rate: 2.84% vs 0.26%

p-value: p=<0.01

Underweight adults with hypertension face a substantially amplified risk of major adverse cardiovascular events, highlighting the need for careful risk assessment in this specific population.

Limitations

Retrospective design precludes establishing a cause-and-effect relationship
Blood pressure and BMI classifications relied on single baseline measurements, potentially leading to misclassifications
Residual misclassification of outcomes despite using validated claims-based algorithms
Cohort predominantly included employed working-age individuals, limiting generalizability to older or unemployed populations
Potential selection bias from excluded participants
Death may have acted as a competing event for individual non-fatal outcomes
Potential differential outcome ascertainment bias due to varying opportunities for medical evaluation
Unavailability of data on potential confounders such as dietary factors, physical activity, and socioeconomic status

Cite This Study

Kawano et al. (2026) conducted a cohort in Hypertension and Underweight (n=6,262,298). Underweight combined with stage 2/3 hypertension vs. Normal weight with normal blood pressure was evaluated on Major adverse cardiovascular events (MACEs) within 10 years (HR 5.01, 95% CI 4.23-5.93, p=<0.01). Underweight combined with stage 2/3 hypertension significantly increased the risk of major adverse cardiovascular events (HR 5.01) compared to normal weight with normal blood pressure.

synapsesocial.com/papers/6a969a7f535111e2d4ce8cc9 https://doi.org/10.1038/s41440-026-02781-8

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September 1, 2026Hypertension ResearchOpen Access

Underweight with stage 2/3 hypertension linked to ~400% higher MACE risk vs normal weight and BP.

View Full Paper

Ask AI

Bookmark

Why the study?

Does body mass index modify the risk of major adverse cardiovascular events across blood pressure categories in adults without prior cardiovascular disease?

Population

6,262,298 adults without prior cardiovascular disease, chronic renal failure, dialysis, or antihypertensive…

Comparison

Underweight across different blood pressure… vs Normal weight with normal blood pressure

Design

Cohort

Follow-up

median 1,183 days

Key result

Underweight combined with stage 2/3 hypertension significantly increased the risk of major adverse cardiovascular events (HR 5.01) compared to normal weight with normal blood pressure.

Authors

TKTakahisa Kawano TSTomohisa Seki HAHiroaki Araie

Discussion

Member takes

Overview

Underweight adults with stage 2/3 hypertension warrant careful risk assessment; extends obesity-focused data but leaves open causal mechanisms and targeted interventions.

Key Points

To evaluate whether the 10-year risk of major adverse cardiovascular events associated with body mass index differs across categories of blood pressure.
Analyzed nationwide medical claims data from Japan (2005–2023) involving 6,262,298 adults without prior cardiovascular disease, chronic renal failure, dialysis, or baseline antihypertensive use.
Categorized blood pressure into five tiers and body mass index into underweight, normal weight, overweight, and obesity.
Used multivariable Cox proportional hazards models to assess 10-year risk of major adverse cardiovascular events across combined categories over a median follow-up of 1,183 days.
A total of 34,034 major adverse cardiovascular events occurred over the follow-up period.
Underweight status was associated with a blood pressure-dependent increase in risk, with hazard ratios escalating from 1.14 (95% CI, 1.07–1.22) in normal blood pressure to 5.01 (95% CI, 4.23–5.93) in stage 2/3 hypertension relative to normal weight with normal blood pressure.
A statistically significant interaction occurred between body mass index and blood pressure categories in predicting major cardiovascular outcomes.

Study Design

Type

Cohort (n=6,262,298)

Multicenter

Yes

Structured PICO

Does body mass index modify the risk of major adverse cardiovascular events across blood pressure categories in adults without prior cardiovascular disease?

Population

Exposure

Underweight (<18.5 kg/m²) across different blood pressure categories (normal, high-normal, elevated, stage 1 hypertension, stage 2/3 hypertension)

Comparator

Normal weight (18.5–24.9 kg/m²) with normal blood pressure (<120 and <80 mmHg)

Outcome

Major adverse cardiovascular events within 10 yearscomposite

Main Result

Hazard Ratio: 5.01 (95% CI 4.23–5.93)

Absolute Event Rate: 2.84% vs 0.26%

p-value: p=<0.01

Underweight adults with hypertension face a substantially amplified risk of major adverse cardiovascular events, highlighting the need for careful risk assessment in this specific population.

Limitations

Retrospective design precludes establishing a cause-and-effect relationship
Blood pressure and BMI classifications relied on single baseline measurements, potentially leading to misclassifications
Residual misclassification of outcomes despite using validated claims-based algorithms
Cohort predominantly included employed working-age individuals, limiting generalizability to older or unemployed populations
Potential selection bias from excluded participants
Death may have acted as a competing event for individual non-fatal outcomes
Potential differential outcome ascertainment bias due to varying opportunities for medical evaluation
Unavailability of data on potential confounders such as dietary factors, physical activity, and socioeconomic status

Cite This Study

synapsesocial.com/papers/6a969a7f535111e2d4ce8cc9 https://doi.org/10.1038/s41440-026-02781-8

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

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