Hypertension is one of the most important risk factors for cardiovascular disease (CVD) worldwide, and as such it constitutes a serious threat to cardiovascular health [1]. Hypertension’s complications, including heart disease, stroke, and renal disease, were estimated by the WHO to account for over 9 million deaths annually [2]. As well as increasing cardiovascular events, hypertension has also been associated with dementia and cognitive decline [3]. Early identification and treatment of hypertension are therefore critical for the prevention of CVD and its reduction in mortality.

The cardiometabolic index (CMI) is a comprehensive indicator that is strongly associated with metabolic diseases such as diabetes and is also related to an increased risk of cardiovascular and cerebrovascular events, including stroke [4, 5]. The CMI offers a quantitative approach to the assessment of cardiometabolic risk by incorporating the ratios of waist circumference to height, and triglycerides to high-density lipoprotein cholesterol. A higher value of CMI indicates greater cardiometabolic risk, and detects normal-weight but metabolically abnormal individuals, i.e., metabolically obese normal weight (MONW) individuals [6, 7]. CMI provides useful data in the primary screening of high-risk patients, and in the clinical setting is mainly used to ascertain risk for metabolic syndrome, diabetes, and CVD [4, 8, 9].

Although previous studies have explored the relationship between cardiovascular risk and CMI [10, 11], the relationship between CMI and clinic blood pressure (BP) is uncertain. Clarification of this relationship should provide significant insights into the metabolic processes involved in the determination of BP, as well as new strategies for its management. The predictive value of CMI for cardiovascular events could also create new avenues for the prevention and treatment of CVD. In the present study, we therefore utilized the National Health and Nutrition Examination Survey (NHANES) database to investigate the correlation between CMI and clinical BP. Our aim was to provide a scientific foundation for the improvement of CVD prevention and control strategies.

This study used the NHANES database to explore the correlation between CMI and clinic BP. Multivariate regression analysis found that CMI was positively correlated with both SBP and DBP. Moreover, a consistent relationship remained across different age, gender, and race subgroups. The significant association observed between CMI and BP possibly reflects common metabolic pathways and biological mechanisms.

Threshold effect analysis revealed a non-linear relationship between CMI and BP, with critical thresholds identified for CMI. For SBP, an inflection point was observed at a CMI value of 6.83, indicating that CMI increases when SBP is below this threshold, but decreases above it. For DBP, an inflection point was observed at a CMI value of 2.81, and a similar non-linear relationship was observed between CMI and DBP. The results suggest that biological thresholds may play a role in modulating the relationship between CMI and BP. This is likely to be related to the complex mechanisms of BP regulation, including changes in sensitivity to metabolic factors across different metabolic states.

The non-linear relationship observed here may be attributed to several underlying mechanisms. First, when CMI is at a lower level, the metabolic abnormalities reflected by CMI (e.g., elevated triglycerides, low HDL-C, and increased waist-to-height ratio) primarily influence BP through inflammation [17] and endothelial dysfunction [18], resulting in a positive correlation between CMI and BP. Specifically, these metabolic abnormalities trigger systemic inflammatory responses that increase pro-inflammatory cytokines (e.g., tumor necrosis factor‌ (TNF)-$\alpha$, interleukin (IL)-6) while reducing anti-inflammatory adipokines (e.g., adiponectin). The inflammatory markers impair endothelial function by reducing nitric oxide (NO) bioavailability [19], leading to decreased vasodilation and increased vascular stiffness, thereby raising BP. Additionally, an increased waist-to-height ratio is indicative of abdominal obesity, which is closely associated with insulin resistance [20], further exacerbating endothelial dysfunction and promoting hypertension.

However, when CMI exceeds certain thresholds, the relationship between CMI and BP changes significantly. The present study found distinct inflection points of 6.83 for SBP and 2.81 for DBP. This phenomenon may be related to the complex mechanisms of BP regulation. When CMI exceeds 6.83, it becomes negatively correlated with SBP, possibly because under extreme metabolic abnormalities (e.g., severe obesity or insulin resistance), the body activates a series of counter-mechanisms that prevent further increases in BP. For example, the renin-angiotensin-aldosterone system (RAAS) may be activated, but as metabolic abnormalities worsen, the feedback regulation mechanisms for RAAS may change, thereby weakening its regulatory effect on BP and even leading to paradoxical responses [21]. Additionally, the sympathetic nervous system (SNS) is often overactivated in metabolic syndrome, which may lead to receptor fatigue or desensitization when metabolic abnormalities reach a certain level [22], thus reducing its pressor effects.

When CMI exceeds 2.81, it also becomes negatively correlated with DBP. This may be related to further deterioration of endothelial function. When CMI is low, endothelial dysfunction is mainly manifested as reduced NO bioavailability, leading to decreased vasodilation. However, as CMI increases, endothelial dysfunction may worsen [18], reducing the responsiveness of blood vessels to vasodilatory signals and even offsetting the effects of vasoconstriction. Additionally, as metabolic abnormalities worsen, adipose tissue may secrete more anti-inflammatory factors (e.g., adiponectin) [23], which may improve endothelial function and reduce BP by reducing oxidative stress.

The different responses of SBP and DBP to changes in CMI may also be due to their different physiological mechanisms in relation to the formation and regulation of BP. SBP mainly reflects the peak BP during cardiac contraction, whereas DBP mainly reflects the maintenance of BP during cardiac relaxation. Therefore, SBP and DBP may have different sensitivities to metabolic abnormalities, leading to different correlations when CMI exceeds certain thresholds.

Interaction analysis revealed a significant interaction between CMI and gender for SBP (p = 0.0054), indicating the association between CMI and SBP differs between males and females. Specifically, the effect of CMI on SBP was stronger in females ($\beta$ = 5.74, 95% CI: 4.17–7.31, p 0.001) than in males ($\beta$ = 0.51, 95% CI: –0.13–1.14), suggesting that gender plays a crucial role in modulating the relationship between CMI and SBP. The stronger association in females may be related to differences in cardiovascular physiology and metabolic characteristics, such as the protective effects of estrogen before menopause [24], and differences in lipid metabolism and insulin sensitivity [25, 26]. Our analysis did not reveal a significant interaction between CMI and age for SBP, indicating the relationship between CMI and BP was consistent across different age groups. However, age-related physiological changes such as increased vascular stiffness and decreased kidney function may still influence BP regulation [27, 28, 29].

Several studies have investigated the relationship between CMI and BP across different regions and populations. A study comprising 11,400 adults in China reported a significant positive association between CMI and hypertension [11]. Moreover, for each one standard deviation increase in CMI, the risk of hypertension increased by 35.6% in women and 31% in men. Another study of 15,453 participants in Japan revealed a nonlinear relationship between CMI and the risk of hypertension and other metabolic diseases [30]. The risk was significantly increased when CMI was low (1.01), but the association weakened when CMI was high. A study based on adolescents found that CMI can effectively predict hypertension, with an AUC value from receiver operating characteristic (ROC) curve analysis of 0.710, indicating an acceptable degree of accuracy in screening for hypertension risk [10]. These studies vary in design and methodology, with some having cross-sectional designs and others being longitudinal cohort studies. Although most previous study results are consistent with our findings, some studies did not find significant associations, possibly due to differences in genetic background, lifestyle, dietary habits, and methodological differences in BP measurement. The methodological advantage of the current study lies in its use of the NHANES database, which is a representative national sample and thus more broadly generalizable. Additionally, our study revealed nonlinear characteristics and specific thresholds of the relationship between CMI and BP through threshold effect analysis. This offers new support for the clinical application of CMI, while contributing to a more precise assessment of individual cardiovascular risk.

As a comprehensive indicator of metabolic health, CMI may be related to BP through various biological pathways. Firstly, the ratio of triglycerides to high-density lipoprotein cholesterol in CMI reflects lipid abnormalities, which have been associated with endothelial dysfunction and vascular inflammation [31]. Endothelial dysfunction leads to a decrease in the vascular dilation capacity, thereby increasing the risk of cardiovascular events. Secondly, the waist-to-height ratio in CMI indicates abdominal obesity, a key component of metabolic syndrome, and is associated with insulin resistance and chronic inflammatory states [32, 33]. Furthermore, CMI is closely associated with the progression of vascular atherosclerosis. Studies have shown that the increase in CMI not only reflects metabolic abnormalities but may also accelerate the progression of atherosclerosis by promoting endothelial dysfunction [34] and inflammatory responses [35]. Wakabayashi et al. [6] further confirmed that CMI is significantly associated with the progression of atherosclerosis in patients with peripheral arterial disease. Therefore, CMI may serve as a potential indicator for assessing the risk of atherosclerosis. These pathophysiological processes collectively promote an elevated BP and increased cardiovascular risk.

The strengths of this study lie in its large sample size and national representativeness associated with the NHANES database, thereby enhancing the generalizability of our findings. Additionally, we employed multivariate regression analysis to control for several potential confounding factors, adding strength to the reliability of the results. However, there are also some limitations to this study. First, due to the cross-sectional nature of the NHANES data, causality from CMI to BP is not possible to determine. Second, although we controlled for different covariates, there could still be some unmeasured confounders such as genetic factors and psychosocial traits that could potentially affect the relationship between CMI and BP. Last but not least, although the computation formula for CMI is simple and easy to implement, application of it in diverse populations still needs further validation. It is also noteworthy that 2441 had missing information on smoking history. This may have introduced some bias and limited the generalizability of our findings, as smoking is a confirmed risk factor for hypertension and cardiovascular diseases. Future studies need to be geared towards addressing this shortcoming through the gathering of more detailed data on smoking practices.

Finally, this study reports novel evidence for the relationship between CMI and clinic BP and the potential of CMI for cardiovascular risk stratification. Even though our observations are limited by their nature, they provide the foundation for subsequent studies that might have important clinical implications for managing hypertension and other related disorders.

The CMI was found to be highly and positively correlated with clinic BP in the general United States population, which indicates its potential utility as a valuable predictor of cardiovascular risk. The correlation is particularly valuable in the identification of high-risk patients for hypertension and related cardiovascular complications. CMI follow-up can further elucidate how the BP of an individual is related to his or her metabolic health.

The threshold effects revealed in this research indicated substantial non-linear correlations between CMI and BP, and the influence of CMI on BP based on whether CMI was greater or less than specific thresholds. These data suggest that the treatment of hypertension should be tailored to an individual’s CMI score. For instance, when CMI is subthreshold, it should be addressed to manage other cardiovascular risk factors, whereas when CMI is over the threshold, intensified BP surveillance and treatment are appropriate.

Significant gender interactions with CMI for SBP emphasize the contribution of individual factors to the modification of the CMI-BP relationship. These interactions indicate that the association between CMI and BP is not uniform across the population, and can be influenced by factors such as gender. Therefore, a multi-factorial comprehensive analysis involving CMI and demographic and clinical factors is essential for identifying high-risk subgroups accurately and guiding targeted interventions.

CMI, cardiometabolic index; NHANES, National Health and Nutrition Examination Survey; SBP, systolic blood pressure; DBP, diastolic blood pressure; CVDs, cardiovascular diseases; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; WHtR, waist-to-height ratio; BMI, body mass index; CRP, C-reactive protein; PIR, poverty income ratio; ROC, receiver operating characteristic; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system.

Publicly available datasets were analyzed in this study. These data can be found at: https://www.cdc.gov/nchs/nhanes/about/erb.html.

LH: Collected the data, conducted the investigation, provided resources, and wrote the original draft of the manuscript. LH also contributed to the review and editing of the manuscript. LS: Conducted formal analysis and contributed to the methodology. HP: Contributed to the conception of the research, developed the methodology, provided software support, and critically reviewed and edited the manuscript. CZ: Designed the research, contributed to the methodology, provided software support, wrote the original draft of the manuscript, and critically reviewed and edited the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study utilized secondary analyses of publicly available and de-identified data obtained from NHANES. The protocols of NHANES adhered to the ethical guide lines of the 1975 Declaration of Helsinki and received approval from the NCHS research ethics review board. All patients/participants or their families/legal guardians provided informed consent.

This research was funded by the Zhejiang Province Traditional Chinese Medicine Scientific Research Fund (2023ZL700), Clinical Key Specialty Construction Project of Zhejiang Province–Cardiovascular Medicine (2024-ZJZK-001).

The authors declare no conflict of interest.