The relationships between lipid ratios and arterial stiffness

1. INTRODUCTION

Large artery stiffness plays an important role in the pathogenesis of cardiovascular diseases.1, 2, 3, 4, 5, 6

As these vessels stiffen, there is a reduction in their capacity to buffer the cyclic changes in blood pressure caused by intermittent left ventricular ejection. Reduced elasticity of large arteries leads to systolic hypertension and increases left ventricular workload.1, 2 Concomitantly, diastolic pressure falls, reducing myocardial perfusion and increasing pulsatility, which damages capillaries in high flow organs such as the brain and kidney.4 Various risk factors and biologic processes affect arterial stiffness. Measurements of arterial stiffness may therefore not only provide information about prevalent processes but also valuable insight regarding the cumulative history of risk factor exposure.1, 2

The measurement of pulse wave velocity (PWV) is generally accepted as the most simple, noninvasive, and reproducible method with which to determine arterial stiffness.1, 2, 3 The basic principle of PWV assessment is that the pulse wave runs along the arterial tree at a speed which depends on the elasticity of the wall itself: the stiffer (ie, less elastic) the wall, the higher the velocity of propagation.

The PWV can be determined by measuring the pulse transit time from the pressure waveforms at the two sites along a vascular segment, usually the carotid and femoral arteries. The distance is divided by the time delay between the proximal and the distal waves. The physical distance between the two sites is measured on the surface of the body using a tape measure, and the velocity measurement is the ratio of distance traveled to elapsed time.1, 2

Carotid‐femoral PWV (cfPWV) is considered a global estimate of arterial PWV through the entire aorta. It is considered the gold standard measure of aortic stiffness.

The aorta is a major vessel of interest when determining regional arterial stiffness, since the aorta and its first branches are what the left ventricle “sees” and are the vessels responsible for most of the pathophysiological effects of arterial stiffness.1, 2, 3 Moreover, there is a large and very consistent body of evidence indicating that aortic PWV is strongly and independently related to other indices of organ damage1, 2, 3, 4, 5, 6, 7, 8 and to the development of fatal and nonfatal cardiovascular events.1, 2, 3, 5, 6, 7 The independent prognostic value of cfPWV was convincingly confirmed by an individual participant meta‐analysis,5 in which an increase in one standard deviation change in log cfPWV was related to a 28% increase in cardiovascular mortality after adjustment of additional risk factors. There is also evidence that patients at intermediate risk could be reclassified into a higher or lower cardiovascular risk category when cfPWV is measured.5 By contrast, PWV measured outside the aortic track, at the upper or lower limbs, has no predictive value.1, 2, 3, 4, 5

For the above‐mentioned reasons, in the current guidelines of the European Society of Hypertension and the European Society of Cardiology for the management of arterial hypertension, aortic PWV is recommended to be evaluated as a measure of asymptomatic organ damage and for the stratification of global cardiovascular risk.3 The assessment of cfPWV as a vascular biomarker is also recommended in the recent European Society of Cardiology/Association for Research into Arterial Structure and Physiology position paper6 and in the European Association for the Study of Diabetes guidelines.7

However, cfPWV measurement has not become part of the daily routine in clinical work so far, probably because the methods available are sometimes complicated and time‐consuming, partly operator dependent, and can cause discomfort for the patient with the manipulation in the inguinal region. New instruments, using an oscillometric technique and a procedure that takes only 2 to 3 minutes, seem to offer a solution allowing estimation of aortic PWV by using a simple upper arm cuff.2, 7, 9 Some of these devices have versions developed for 24‐hour blood pressure and arterial stiffness monitoring, opening a new field of research interest.9, 10 Even if some of these methods provide PWV values very close to those recorded by widely accepted and clinically validated devices or by invasive techniques,2, 10 none of these new methods are currently recommended by any scientific society as an alternative to cfPWV because there is limited evidence of cardiovascular outcome prediction in longitudinal studies.9, 10, 11

Another index of arterial stiffness is brachial‐ankle PWV (baPWV). This parameter, which has been used broadly in Japan and China, theoretically may be a less ideal measure of large artery stiffness than aortic PWV, being a hybrid measure that integrates the mechanical properties from both the central and peripheral arteries.6, 12 It is measured with a volume‐plethysmographic device using four cuffs placed on both arms (brachial) and ankles, connected to plethysmographic and oscillometric sensors, recording the brachial and posterior tibial pressure waveforms. Travel distance is calculated using the path lengths from the suprasternal notch to the brachium and from the suprasternal notch to the ankle with a correction for the height of the individual using validated equations.12

The baPWV has been shown to be closely correlated with the aortic PWV,13 however, and meta‐analysis of cohort studies has shown that a 1‐m/s increase in baPWV is associated with a 12% increase in the risk of cardiovascular events.14 In cases of peripheral arterial disease, the reliability of baPWV measurement is attenuated.12

Several cross‐sectional studies showed that arterial stiffness, when assessed as aortic PWV or baPWV, is closely associated with age and blood pressure1, 2 which may account for up to 70% of its variance,15 whereas the correlations with other established cardiovascular risk factors such as diabetes mellitus,1, 2 metabolic syndrome,1, 2, 16 renal dysfunction,1, 2, 5, 8, 11 smoking habit,1, 2 and dyslipidemias1, 2 were less strong or not significant.

In the current issue of the Journal, Wen and coworkers17 assessed the relationships of lipids and their ratio with baPWV in a wide group of young Chinese men. They found that lipid ratios were better associated with baPWV than conventional single lipid parameters. In multivariate analyses, the triglyceride (TG)/high‐density lipoprotein cholesterol (HDL‐C) ratio appears to be most closely associated with arterial stiffness, followed by the non–HDL‐C/HDL‐C ratio, and then total cholesterol/HDL‐C and TG.17

Most cross‐sectional studies evaluating the associations between arterial stiffness and single lipid parameters, especially total cholesterol or low‐density lipoprotein cholesterol, found weak or no significant relationships.

These findings are not surprising if one considers that, although the association of total cholesterol and low‐density lipoprotein cholesterol with atherosclerosis is firmly established, the concepts of arterial wall stiffness (arteriosclerosis) and atherosclerosis need to be distinguished, with the former chiefly a disease of the media, related to normal or accelerated aging, and the latter principally a disease of the intima, affecting the vessel in a patchy manner, leading to the buildup of fatty plaques.3, 6

Both tend to coexist because they share similar pathobiological processes, and widespread phenomena of atherosclerosis can also cause a certain degree of arterial stiffness, mostly in the presence of extended calcifications.

In a systematic review from 2009, low HDL‐C and increased TG were significantly associated with arterial stiffness in only four of 37 and one of 38 studies, respectively.15

Only a few studies assessed the relationships between lipid ratios and PWV.1, 2, 12, 18, 19, 20, 21 In a previous study performed in 1498 apparently healthy Chinese adults, Wen and colleagues18 observed positive relationships between TG/HDL‐C quartiles and increased baPWV.

In agreement with the current and the previous observations of Wen and coworkers, high TG/HDL‐C was associated with increased arterial stiffness in Japanese patients with diabetes19 and in a large sample of a Chinese community‐dwelling population.20 Moreover, Urbina and colleagues21 found that TG/HDL‐C was independently associated with cfPWV in 893 adolescents and young adults.

Several potential mechanisms may explain the link between TG/HDL‐C and arterial stiffness.17 Plasma TG and HDL‐C concentrations are independently related to insulin‐mediated glucose disposal, and many studies suggest that the TG/HDL‐C ratio provides a simple way to identify individuals who are insulin resistant and at increased cardiometabolic risk21, 22, 23

Insulin resistance states are also characterized by an imbalance between the endothelial production of two important regulators of arterial stiffness, such as nitric oxide and endothelin‐1, whose levels are reduced and increased, respectively.24 Moreover, insulin resistance and chronic hyperinsulinemia increase the local activity of the renin‐angiotensin‐aldosterone system and expression of angiotensin II receptors in vascular tissue, thus leading to vessel wall hypertrophy and fibrosis, which reduce arterial elasticity.24 TG/HDL‐C is also regarded as the strongest correlate of small dense low‐density lipoprotein particles, which, compared with larger low‐density lipoprotein particles, exhibit a greater negative impact on endothelial function and this may potentially impair arterial distensibility.

2. CONCLUSIONS

The article by Wen and colleagues confirms the elusive relationships of the traditional single lipid parameters with the elastic properties of the arterial walls and highlights the associations of arterial stiffness with lipid ratios, especially the TG/HDL ratio. This correlation may partly mediate the enhanced cardiovascular risk associated with an increased TG/HDL‐C ratio. Further studies are needed to assess the causal mechanisms of the relationships reported by Wen and coworkers and to test whether therapeutic targeting of TG and HDL‐C levels might improve arterial elasticity.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

Mulè G, Nardi E, Geraci G, Schillaci MK, Cottone S. The relationships between lipid ratios and arterial stiffness. J Clin Hypertens. 2017;19:777–779. 10.1111/jch.13030