Cf-PWV and TyG Index Study

Introduction

Hypertension remains a major global health problem and a leading contributor to cardiovascular morbidity and mortality. Large epidemiological studies have demonstrated a continuous and graded relationship between blood pressure levels and cardiovascular events, including myocardial infarction, stroke, and heart failure. However, traditional office blood pressure measurements do not fully capture the complexity of cardiovascular risk.

Arterial stiffness has emerged as a key marker of vascular aging and cardiovascular risk. Carotid-femoral pulse wave velocity (cf-PWV) is considered the gold standard non-invasive method for assessing aortic stiffness. Increased cf-PWV reflects cumulative vascular damage resulting from structural and functional alterations in the arterial wall, including elastin degradation, collagen deposition, vascular calcification, and endothelial dysfunction.

Insulin resistance is a central mechanism linking metabolic disorders to vascular dysfunction. It is associated with reduced nitric oxide bioavailability, increased sympathetic activity, chronic low-grade inflammation, and vascular remodeling. The triglyceride-glucose (TyG) index has been validated as a reliable surrogate marker of insulin resistance and has shown consistent associations with cardiometabolic outcomes.

Derived indices incorporating anthropometric parameters, such as TyG-WC, TyG-BMI, and TyG-WHtR, have been proposed to better capture the interaction between metabolic dysfunction and central adiposity. In addition, composite indices such as the body roundness index (BRI), metabolic score for insulin resistance (METS-IR), and cardiometabolic index (CMI) integrate multiple physiological domains and may provide incremental value in cardiovascular risk stratification.

Circadian blood pressure variation represents another important dimension of cardiovascular physiology. Blood pressure follows a daily rhythm, with a physiological increase in the early morning associated with sympathetic activation and hormonal changes. This phenomenon, known as the morning blood pressure surge (MBPS), has been associated with increased risk of cardiovascular events when exaggerated.

Arterial stiffness may amplify this morning increase in blood pressure due to reduced arterial compliance and impaired buffering of pulsatile flow. In addition, metabolic dysfunction may alter autonomic regulation and baroreflex sensitivity, further influencing circadian blood pressure patterns.

Despite strong biological plausibility, the integrated relationship between metabolic indices, arterial stiffness, and morning blood pressure parameters remains insufficiently explored. Understanding these interactions may improve early identification of individuals at increased cardiovascular risk.

Objectives

Primary Objective

To evaluate the association between arterial stiffness, measured by carotid-femoral pulse wave velocity, and the triglyceride-glucose (TyG) index.

Secondary Objectives

To assess associations between cf-PWV and TyG-derived indices (TyG-WC, TyG-BMI, TyG-WHtR); To evaluate associations between cf-PWV and composite metabolic indices (METS-IR, CMI, BRI); To investigate relationships between metabolic indices and morning blood pressure levels; To assess associations between metabolic indices and morning blood pressure surge (MBPS); To compare the performance of different metabolic indices in identifying increased arterial stiffness and morning hemodynamic load.

Methods Study Design and Data Sources

This is an observational, cross-sectional study with a prospective component, designed to evaluate the integrated relationship between metabolic indices, arterial stiffness, and circadian blood pressure patterns. The study adopts a hybrid design, combining data from two complementary sources: (1) previously collected data from an ethically approved research protocol and (2) prospectively collected data obtained under a standardized protocol.

Previously collected data will be used as secondary data, ensuring full anonymization and confidentiality. Prospectively recruited participants will provide written informed consent prior to inclusion. To ensure comparability, identical measurement protocols and definitions will be applied across both datasets.

Study Population

The study will include adults aged 18 to 65 years referred for ambulatory blood pressure monitoring (ABPM) as part of routine clinical evaluation in a specialized cardiovascular center. Participants will be included regardless of sex.

Only individuals not receiving antihypertensive treatment at the time of evaluation will be eligible for inclusion, in order to minimize the confounding effects of pharmacological therapy on arterial stiffness, metabolic indices, and circadian blood pressure patterns.

Participants will be classified according to 24-hour ABPM results into:

Normotensive individuals Untreated hypertensive individuals (defined as 24-hour mean blood pressure ≥130/80 mmHg) Clinical and Anthropometric Assessment

Baseline clinical data will include age, sex, and relevant medical history. Anthropometric measurements will be obtained using standardized procedures:

Body weight and height will be measured with participants wearing light clothing and no shoes; Body mass index (BMI) will be calculated as weight (kg) divided by height squared (m²); Waist circumference will be measured at the midpoint between the lowest rib and the iliac crest using a flexible tape measure.

In addition, the Body Roundness Index (BRI) will be calculated using a validated geometric formula incorporating waist circumference and height, providing an estimate of body fat distribution and central adiposity.

Office Blood Pressure Measurement

Office blood pressure (OBP) will be measured using a validated automated oscillometric device under standardized conditions. Measurements will be obtained after at least 5 minutes of seated rest, with the participant in a quiet environment.

Three consecutive readings will be recorded at short intervals, and the average of these measurements will be used for analysis. Heart rate will be recorded simultaneously.

Ambulatory Blood Pressure Monitoring (ABPM)

All participants will undergo 24-hour ABPM using a validated oscillometric device, applied to the non-dominant arm with an appropriately sized cuff.

The device will be programmed to obtain measurements:

Every 20 minutes during daytime (awake period) Every 30 minutes during nighttime (sleep period)

Daytime and nighttime periods will be defined based on individual sleep diaries. Only recordings meeting established quality criteria will be considered valid.

Mean systolic and diastolic blood pressure values will be calculated for:

24-hour period Daytime period Nighttime period

Hypertension will be defined based on a 24-hour mean blood pressure ≥130/80 mmHg.

Morning Blood Pressure and Morning Surge Definitions

Morning systolic and diastolic blood pressure will be defined as the average of readings obtained during the first two hours after awakening.

Morning blood pressure surge (MBPS) will be assessed using two complementary definitions:

Sleep-through MBPS (ST-MBPS): difference between morning systolic BP and the lowest nocturnal systolic BP value (including adjacent readings); Prewaking MBPS (PW-MBPS): difference between morning systolic BP and the average systolic BP during the two hours preceding awakening.

These indices will be analyzed as continuous variables and may also be evaluated across quartiles of metabolic indices.

• Morning systolic blood pressure [Time frame: Average systolic blood pressure during the first two hours after awakening, obtained from 24-hour ambulatory blood pressure monitoring (ABPM).]
• Morning diastolic blood pressure [Time frame: Average diastolic blood pressure during the first two hours after awakening, obtained from ABPM.]
• Sleep-through morning blood pressure surge [Time frame: Difference between morning systolic blood pressure and the lowest nocturnal systolic blood pressure value.]
• Prewaking morning blood pressure surge [Time frame: Difference between morning systolic blood pressure and the average systolic blood pressure during the two hours preceding awakening.]