What is the clinical evidence from this study?

Study design: Observational. Population: Hypertension with elevated HDL-C (n=98). Intervention: Hypertension vs. Normotensive subjects. Primary outcome: Percent distribution of Large-HDL (L-HDL) subfractions (p=<0.001).

What does this research mean for the field?

Hypertensive patients have lower levels of large high-density lipoprotein (L-HDL) and higher levels of small high-density lipoprotein (S-HDL) compared to normotensive subjects, indicating an increased cardiovascular disease risk. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

February 6, 2026

The role of the plasma high density lipoprotein subfraction profile in hypertensive patients with elevated high density lipoprotein levels

Q: What are the key findings of this study?

Hypertension in patients with elevated HDL-C was associated with a lower percentage of large-HDL particles compared to normotensives (29.8% vs 36.6%, p<0.001).

Q: What does this research mean for the field?

Hypertensive patients have lower levels of large high-density lipoprotein (L-HDL) and higher levels of small high-density lipoprotein (S-HDL) compared to normotensive subjects, indicating an increased cardiovascular disease risk. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Q: What question did this study set out to answer?

This research aimed to assess the HDL subfraction profile in hypertensive patients with elevated HDL levels and its prognostic significance.

Key Result

Hypertension in patients with elevated HDL-C was associated with a lower percentage of large-HDL particles compared to normotensives (29.8% vs 36.6%, p<0.001).

Key Points

This research aimed to assess the HDL subfraction profile in hypertensive patients with elevated HDL levels and its prognostic significance.
Studied 74 hypertensive patients and 24 normotensive subjects with HDL-C ≥55 mg/dl.
Measured cholesterol, HDL-C, and triglycerides enzymatically, LDL-C calculated using Friedewald formula.
Separated HDL particles by electrophoresis using Lipoprint System HDL Subfractions Kit.
Assessed aortic stiffness and central blood pressure with carotid-femoral pulse wave velocity.
Tracked cardiovascular events in hypertensive premenopausal females over a 5-year period.
Hypertensive individuals had lower L-HDL distribution compared to normotensives (29.8% vs. 36.6%, p<0.001).
S-HDL distribution was higher in hypertensives (27.3% vs. 20.4%, p<0.001).
Significant negative correlation found between L-HDL and SBP as well as central BP in premenopausal hypertensive females.
No cardiovascular events occurred during the 5-year follow-up among premenopausal hypertensive women.

Study Design

Type

Observational (n=98)

Structured PICO

Does the plasma HDL subfraction profile differ between hypertensive and normotensive subjects with elevated HDL-C levels, and does it predict 5-year cardiovascular events in premenopausal hypertensive females?

Population

98 subjects with HDL-C ≥55 mg/dl, comprising 74 hypertensive patients (mean age 60±13 years, 62 females) and 24 normotensive healthy subjects (mean age 49±14 years, 22 females).

Intervention

Hypertension (observational exposure)

Comparator

Normotensive, apparently healthy subjects

Outcome

Plasma HDL subfraction profile (percent distribution of Large, Intermediate, and Small HDL) and 5-year cardiovascular events in premenopausal hypertensive femalessurrogate

Hypertensive patients with elevated HDL-C have a more atherogenic HDL subfraction profile (lower Large-HDL, higher Small-HDL) compared to normotensives, suggesting HDL-C levels alone may overestimate cardiovascular protection in hypertension.

Main Result

Absolute Event Rate: 29.8% vs 36.6%

p-value: p=<0.001

Abstract

Abstract Background The evaluation of cardiovascular (CV) risk in arterial hypertension includes the estimation of high-density lipoprotein (HDL-C) which is considered a favorite CV factor. However, the exact role of the HDL-C subfraction profile in the pathogenesis of atherosclerosis, especially in higher than usual HDL-C levels (60 mg/dl), is currently under investigation. The aim of this study was to evaluate the plasma HDL subfraction profile of elevated HDL-C levels in hypertensive patients compared to normotensive subjects and its 5-year prognostic role in premenopausal hypertensive females. Population and Methods: We studied 74 hypertensive patients (60+13 years, 62 females) and 24 normotensives, apparently healthy subjects (49+14 years, 22 females). Subjects in both groups had HDL-C ≥55 mg/dl. Cholesterol, HDL-C, and triglycerides (TG) were determined enzymatically while low density lipoprotein (LDL-C) was calculated using the Friedewald formula. Plasma HDL particles were separated and determined electrophorically using Lipoprint System HDL Subfractions Kit. Aortic stiffness (c-f PWV) and central BP (cBP) were evaluated by carotid-femoral pulse wave velocity (Complior apparatus). We investigated any CV events in hypertensive premenopausal females at 5 years post-baseline evaluation. Results We found that hypertensive patients had increased age, BMI, office systolic and diastolic BP and PWV compared to normotensives subjects. Regarding HDL-C, 10 fractions were separated: fractions 1-3 were denoted as Large-HDL (L-HDL), fractions 4-7 constituted the Intermediate-HDL (I-HDL), and fractions 8-10 were denoted as Small-HDL (S-HDL) subfractions. Although HDL-C levels were similar between groups (76+13 vs. 81+17 mg/dl, p=0.10), the percent distribution (%) of L-HDL was lower in hypertensives compared to normotensives (29.8±4.7% vs. 36.6±6.3%, p0.001), that of I-HDL was similar in both groups and finally the percent distribution of S-HDL was increased in hypertensives (27.3±3.7% vs. 20.4±4.4%, p0.001). We found a significant negative correlation between L-HDL and SBP (rho= -0.48, p=0.01) as well as cBP (rho= -0.52, p=0.008) in premenopausal hypertensive females (n=25, 55 years). However, no CV events were reported after a 5-year follow-up of premenopausal hypertensive females, irrespective of the HDL-C subfractions. Conclusions L-HDL particles, the most non-atherogenic HDL-C subfractions, were reduced in hypertensive patients with elevated HDL-C levels compared to normotensive subjects. Our findings suggest that these hypertensive patients are probably less protected against CV disease compared to normotensive subjects with similar elevated HDL-C levels. Therefore, plasma HDL-subfraction profile might replace in the future the HDL-C evaluation as a better biomarker of CV risk in hypertensive patients. On the other hand, HDL-subfraction profile does not seem to exhibit any mid-term prognostic CV role in premenopausal hypertensive females.Figure 1

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