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Menopause Review/Przegląd Menopauzalny
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Original paper

Relationship of the neutrophil/lymphocyte ratio with cardiovascular risk markers in premenopausal and postmenopausal women

Sebastián Carranza-Lira
1
,
Maryel Montes Montiel
1
,
Karina Ocampo Camacho
1
,
Xiomara Hernández Santana
1
,
Sergio Rosales Ortiz
1
,
Eunice López Muñoz
1
,
Luis Claudio Erick Hernández Ángeles
1

1.
UMAE Gynaecology and Obstetrics Hospital “Luis Castelazo Ayala”, Social Security, Mexican Institute, Mexico DF, Mexico
Menopause Rev 2020; 19(2): 53-60
Online publish date: 2020/07/13
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Introduction

The climacteric is the stage in the life of the woman that precedes and follows the cessation of menstruation (menopause), initially due to the decrease and subsequently to the cessation of estrogen and progesterone production by the ovary [1]. It is known that cardiovascular disease (CVD) is more frequent in older women than in men of the same age [2], and is an important cause of mortality in women. A woman living in the western world has a 46% risk of suffering from atherosclerotic coronary disease in the rest of her life and a 31% risk of dying from coronary heart disease [3, 4]. The symptoms of climacteric can be controlled with the use of hormone therapy whether with estrogen or estrogen plus progestogen, although this has not been recommended for the prevention of CVD [5]. However, it has been observed that estradiol has anti-inflammatory properties in vitro [6] and the use of hormone therapy (HT) in the first 10 years after menopause is not associated with cardiovascular risk as it is when administered after that period of time [7]. Lipid changes and endothelial damage are involved in the genesis of atherosclerosis which is a chronic inflammatory process, due to the inability of the organism to stop an acute inflammatory process [8]. In postmenopause it has been observed that the tumor necrosis factor (TNF) alpha rises, probably in relation to the decrease in estrogen and progesterone, which favors insulin resistance and the modification in fat distribution [9]. The neutrophil/lymphocyte ratio (NLR) is an inflammatory state marker that predicts cardiovascular [10] and renal complications in patients with diabetes [11], as well as mortality due to cardiovascular causes in patients on hemodialysis [12] and in patients with difficult to control hypertension [13]. Likewise, the NLR has been considered as a marker of systemic dysfunction in asymptomatic subjects [14]. The endothelium acts as a barrier and facilitates various processes, due to the expression of various molecules, including nitric oxide (NO) which is produced from L-arginine by NO synthetase and which is activated by various stimuli such as hypoxia, serotonin and increased vascular flow. High lipids levels and insulin resistance have a harmful effect on the endothelium, which is manifested among others by the loss of the endothelial NO activity and may precede CVD for several years [15, 16].

Obesity is closely related to CVD [17], and its prevalence is twice as high in postmenopausal women as in premenopausal women [18]. Obesity has been associated with higher fasting glucose levels, interleukin 6, C-reactive protein, being these last two markers of inflammation, correlating the latter with the number of leukocytes, in addition to the fact that the platelet count is higher in obese [19]. The increase in visceral fat is associated with high levels of triglycerides and low levels of high density cholesterol (HDL-C) [20] as well as with alterations in insulin sensitivity [21], which is an important component of the metabolic syndrome. Some authors have suggested that the detection of visceral fat allows the identification of those patients with high-risk metabolic syndrome [22] since it is associated with inflammation and release of pro-inflammatory cytokines [23]. In the menopausal transition adiponectin decreases and visceral fat is increased which has been associated with insulin resistance and decreased HDL-C.

Abdominal fat can be measured with different methodologies including abdominal ultrasound. In one study it was found that visceral fat correlated positively with systolic blood pressure in the group with carotid intima media thickness (IMT) > 1 mm and which is known to be an indicator of cardiovascular risk [24].

Atherosclerosis is a systemic disease that is responsible for many of the cardiovascular and cerebrovascular events, which are directly related to the increase in IMT in different blood vessels [25]. The carotid artery IMT has been the most studied marker and has been validated by official medical organizations. It has been reported that a 0.1 mm increases in IMT are associated with a 10% to 15% increase in the risk of having a myocardial infarction and from 13% to 18% to have a cerebrovascular event [26].

For endothelial function evaluation there are several non-invasive techniques, one of them is the Doppler ultrasound [27]. The flow-mediated dilation (FMD) in the peripheral arteries after the chemical and/or physical stimulation consist in the regulation in vascular tone and blood flow, which corresponds to that of the coronary arteries and a correlation between coronary abnormalities [28] and brachial artery flow has been reported [29]. Also, subcutaneous fat correlates inversely with FMD that is an indirect marker of the endothelial health status [30].

Recently the measurement of epicardial fat has been used as an indicator of cardiovascular risk and has been correlated with other markers of endothelial dysfunction. This is closely related to visceral fat [31], the metabolic syndrome [32] and is also increased in oophorectomized women [32].

Cardiovascular disease is one of the main causes of death so finding a marker that can be easily applied to a big group of people will be useful to early detect people at risk.

Therefore, the objective of this study was to determine the relationship of the NLR with different markers of cardiovascular risk between pre- and postmenopausal women.

Material and methods

Premenopausal and postmenopausal women who attended the outpatient endocrine gynecology clinic were studied. All were consecutively as they arrived and accepted to participate. In all of them, age (years), associated diseases, concomitant medications, age at the time of menopause (years) were documented. Use of HT, time of use of HT (months), type of HT, age at the beginning of TH (years). Weight (kg), height (meters) were measured and body mass index (weight/height2) was calculated. Likewise, the waist perimeter (cm), the hip perimeter (cm) were measured and the waist-hip ratio (WHR, waist perimeter/hip perimeter) was calculated. Blood pressure (mm Hg), glucose (mg/dl), cholesterol (mg/dl), triglycerides (mg/dl), HDL-C (mg/dl) were measured, and a complete hemogram was done.

The NLR was calculated by dividing the total number of neutrophils by the total number of lymphocytes being normal when ≤ 4, also the platelet/lymphocyte ratio (PLR) was calculated by dividing the total number of platelets by the total number of lymphocytes being normal when ≤ 185 [12, 33].

For the study a Voluson 730 Pro device (General Electric Healthcare, Austria GM GH) was used. All patients underwent abdominal ultrasound with a 5 MHz transducer to measure subcutaneous fat and visceral (intrabdominal) fat. For this the transducer was placed in the midline, 1 cm below the navel and subcutaneous fat was considered as the distance between the skin and the external face of the rectus abdominis muscle (cm) and the visceral fat was considered as the distance from the internal face of the rectus abdominis muscle and the anterior wall of the aorta (cm) [34]. The visceral fat/subcutaneous fat ratio was calculated, being normal when ≤ 0.54 [35].

The carotid IMT was then measured with a 7.5 MHz transducer, in the soft tissue category, locating the carotid artery 1 cm from its bifurcation, the image was maximized, the diameter of the vessel lumen was visualized on the screen and measured the distance between the first and the second echogenic line. The highest given value was used for the analysis and was considered normal when ≤ 1 mm [24].

For epicardial fat measurement a mode M ultrasound was done with a 3.5 MHz transducer considering the hypoechoic space between the outer wall of the myocardium and the visceral layer of the pericardium in the parasternal longitudinal view and perpendicular to the free wall of the right ventricle perpendicular to the aortic ring at the end of the systole in three cardiac cycles [36]. It was considered abnormal when ≥ 5 mm [37-40].

Finally all of them underwent Doppler ultrasound of the brachial artery with a 7.5 MHz transducer. For this, the transducer was placed perpendicularly in the distal third of the brachial artery and the internal diameter was measured (mm), when the double line pattern was clearly seen, the pulsatility index (PI) was calculated: maximum systolic velocity minus minimum diastolic velocity divided by the average velocity during the entire cycle and the resistive index (RI): maximum systolic velocity minus final diastolic velocity divided by the maximum systolic speed The hyperemic stimulus was induced by placing the sphygmomanometer cuff on the right arm and insufflating it up to 50 mm Hg above the maximum systolic pressure for five minutes. Subsequently, the cuff was deflated and removed, 60 seconds later the arterial diameter, the PI and the RI were measured again [41, 42].

Statistical analysis

The results are reported with medians and intervals. The comparison between both groups was carried out with Mann-Whitney U test. Spearman’s correlation analysis of the NLR and the PLR was performed with the subcutaneous fat thickness, visceral fat thickness, IMT, epicardial fat, in addition the baseline arterial diameter, PI and RI were measured at baseline and after the hyperemic stimulus values. For the calculations, the SPSS program for Windows V20 was used. A statistically significant difference was considered when the value of p was < 0.05.

The sample size was calculated with the Medcalc V 18.5 program, considering an α error 0.05 and a β error of 0.1 with a difference between the means of 0.6 and a standard deviation in group 1 of 0.52 and in group 2 of 1.18. A relationship between group 1 and two of 1/1 was considered leaving 38 in the premenopausal group and 38 in the postmenopausal group.

The protocol was authorized by the Ethics in Research Committee and by the Local Research in Health Committee of the UMAE Hospital de Gineco Obstetricia “Luis Castelazo Ayala” from the Social Security Mexican Intitute at Mexico City, with the number R-2018-3606-031, and all patients signed the informed consent form.

The funding of the project was with resources of the hospital and the researchers.

Results

There were included 82 patients, 41 premenopausal (group 1) and 41 postmenopausal (group 2). The age in group 1 was 49 (42-55) years and in group 2 55 (42-86) years p < 0.000. Time since menopause was in group 2 49 (12-588) months. When comparing the premenopausal group with the postmenopausal group as BMI, WHR, glucose, cholesterol, triglycerides and HDL there were no differences between the two groups (Table 1).

Table 1

General data in two groups of women

CharacteristicsPremenopausal
(n = 41)
Postmenopausal
(n = 41)
p
Age (years)49 (42-55)54 (42-86)0.00
How many hot flushes a day3 (1-11)4 (1-20)0.06
Body mass index27.7 (22-42.9)27.1 (19.8-37.8)ns
Waist hip index0.89 (0.71-0.97)0.9 (0.77-0.98)ns
Glucose (mg/dl)95.0 (73.0-127.0)91 (72-107)ns
Cholesterol (mg/dl)203.5 (141-254)196 (105-319)ns
Triglycerides (mg/dl)149.5 (49-316)144 (60-315)ns
HDL-C (mg/dl)50 (38-99)45.5 (30-99)ns

[i] HDL-C – high density cholesterol

When comparing those premenopausal women with and without vasomotor symptoms (VMS), there was no difference in any of the analyzed parameters, while in postmenopausal patients the age was greater in those without VMS (p < 0.000) as well as the time since menopause (p < 0.005) in the other analyzed parameters there were no significant differences (Table 2).

Table 2

General data in pre- and postmenopausal women divided by the presence or absence of vasomotor symptoms (VMS)

CharacteristicsPre without VMS
(n = 10)
Pre with VMS (n = 31)pPos without VMS
(n =13)
Pos with VMS
(n =28)
p
Age (years)47 (42-55)49 (44-54)ns56 (48-86)a52.5 (42-63)b0.004
00bns96 (12-588)c24 (12-300)dns
Time since menopause (months)03 (1-11)ns04 (1-20)ns
27.7 (22.4-42.9)27.7 (22-38.4)ns27.3 (22.8-32.4)27 (19.8-37.8)ns
How many hot flushes a day0.89 (0.71-0.94)0.88 (0.77-0.97)ns0.88 (0.86-0.98)0.91 (0.77-0.97)ns
95 (84-102)94 (73-127)ns94 (85-107)90 (72-105)ns
BMI197.5 (141-237)204 (141-254)ns202 (141-319)194 (105-302)ns
111 (76-305)154 (49-316)ns134 (76-304)145 (60-315)ns
WHR51 (41-73)48 (38-99)ns46 (38-81)45 (30-99)ns

[i] BMI – body mass index, WHR – waist-hip ratio, a,b p < 0.004, c,d p < 0.005

When comparing premenopausal women with postmenopausal women both with hot flashes, the age was greater in postmenopausal patients, as was the number of VMS. In the group without hot flashes there was no difference in any of the analyzed parameters (Table 2).

When comparing the NLR and the PLR between premenopausal and postmenopausal women, no significant differences were found. Also IMT, epicardial fat, subcutaneous fat, visceral fat, visceral fat index/subcutaneous fat did not differ between groups.

In the analysis of the brachial artery Doppler parameters, the arterial diameter, the PI, the RI at baseline and after the hyperemic stimulus, didn’t show significant differences. The same happened when analyzing the differences between baseline and final values of the arterial diameter, PI and RI (Table 3) In those with vasomotor symptoms the proportion of women with normal PLR was greater in those premenopausal when compared with those postmenopausal 60.9% vs 39.1%, p < 0.017.

Table 3

Cardiovascular risk parameters in pre- and postmenopausal women divided by the presence or absence of vasomotor symptoms (VMS)

ParameterPremenopausal
(n = 41)
Postmenopausal
(n = 41)
pPremenopausal
without VMS
(n = 10)
Premenopausal with VMS
(n = 31)
pPostmenopausal without VMS
(n = 13)
Postmenopausal with VMS
(n = 28)
p
NLR1.53 (0.59-2.74)1.59 (0.76-6.96)ns1.38 (0.82-1.86)1.61 (0.59-2.74)ns1.59 (0.76-2.57)1.6 (0.85-6.96)ns
PLR122.2 (23.8-252.1)123.5 (57.49-463.83)ns121.1 (63.2-207.3)122.2 (23.8-252.1)ns114.4 (83.2-224.1)140.2 (57.5-463.8)ns
IMT (mm)0.08 (0.01-1.07)0.07 (0.01-0.7)ns0.07 (0.01-0.15)0.08 (0.02-1.07)ns0.06 (0.01-0.3)0.08 (0.03-0.7)ns
Epicardial fat (mm)0.31 (0.13-0.76)0.3 (0.15-1.9)ns0.31 (0.13-0.41)0.31 (0.15-0.76)ns0.23 (0.15-0.51)0.3 (0.15-1.9)ns
Subcutaneous fat (cm)2.33 (1.14-7.06)2.41 (0.13-7.06)ns2.56 (1.14-3.43)2.1 (1.14 -7.06)ns2.63 (0.99-3.14)2.38 (0.13-7.06)ns
Visceral fat (cm)4.08 (1.6-9.5)4.2 (1.29-8.92)ns4.58 (2.7-8.87)3.91 (1.6-9.55)ns4.05 (1.7-5.89)4.24 (1.29-8.92)ns
VF/SF1.64 (0.42-3.96)1.67 (0.28-18.38)ns1.64 (1.4-3.2)1.77 (0.42-4.0)ns1.8 (0.92-3.52)1.65 (0.28-18.38)ns
Baseline AD (mm)0.28 (0.17-2.04)0.27 (0.14-4.0)ns0.28 (0.17-0.4)0.28 (0.17-2.04)ns0.3 (0.17-0.41)0.26 (0.14-4.0)ns
Baseline PI2.22 (0.79-6.12)2.27 (0.75-6.04)ns2.54 (1.08-5.94)2.05 (0.79-6.12)ns2.27 (1.44-5.34)2.21 (0.75-6.04)ns
Baseline RI0.81 (0.32-1.9)0.81 (0.12-1.29)ns0.85 (0.55-1.9)0.79 (0.32-1.14)ns0.81 (0.7-1.29)0.81 (0.12-1.19)ns
AD post HE (mm)0.32 (0.19-0.46)0.29 (0.16-2.9)ns0.35 (0.22-0.44)0.31 (0.19-0.46)ns0.29 (0.17-0.42)0.29 (0.16-2.9)ns
PI post HE2.29 (1.1-6.0)2.16 (0.57-6.42)ns2.29 (1.93-3.2)2.15 (1.1-6.0)ns2.15 (0.57-5.05)2.17 (1.31-6.42)ns
RI post HE0.81 (0.33-2.82)0.81 (0.65-1.3)ns0.84 (0.76-1.24)0.8 (0.33-2.82)ns0.8 (0.67-1.3)0.82 (0.65-1.1)ns
AD DFB0.05 (–1.75-0.14)0.1 (–1.10-0.66)ns0.06 (–0.04-0.13)0.03 (–1.75-0.14)ns0.0 (–0.11-0.09)0.02 (–1.1-0.66)ns
PI DFB–0.1 (–3.41-1.6)–0.11 (–3.32-5.67)ns–0.15 (–3.41-1.21)–0.1 (–3.4-1.6)ns–0.11 (–3.32-1.48)–0.06 (–3.06-5.67)ns
RI DFB0.0 (–1.05-2.5)–0.02 (–0.35-58)ns0.01 (–1.05-0.33)0.0 (–0.57-2.5)ns–0.02 (–0.29-0.44)–0.01 (–0.35-0.58)ns

[i] NLR – neutrophil/lymphocyte ratio, PLR – platelet/lymphocyte ratio, VF – visceral fat, SF – subcutaneous fat, AD – arterial diameter, AD – arterial diameter, PI – pulsatility index, RI – resistance index, DFB – difference final and baseline

When comparing premenopausal women with and without VMS there were no differences in the analyzed parameters and the same happened when comparing premenopausal women with postmenopausal women with and without VMS. Only the number of neutrophils were significantly more numerous in the premenopausal group with VMS 3.6 (2.4-5.6) than in the premenopausal group without VMS 2.9 (2.0-4.3), p < 0.042.

In premenopausal and postmenopausal women no differences were found between the analyzed parameters after dividing according to BMI. After dividing to WHR in premenopausal women statistical significant difference was found in the difference between final and baseline brachial artery diameter 0.08 (–0.08-0.13) vs –1.75 (–0.14) p < 0.052.

In the premenopausal group there was a correlation between the NLR and the cholesterol level 0.303, p < 0.057, and with the triglycerides 0.376, p < 0.017. Also there was among the PLR with the baseline arterial diameter 0.352, p < 0.024, with the baseline IR 0.315, p < 0.045 and with post-hyperemic stimulus RI 0.394, p < 0.011.

In the postmenopausal group there was between NLR and baseline RI 0.336, p < 0.032 between NLR and the difference between final and baseline RI –0.371, p < 0.017. Between the PLR and the number of hot flashes per day –0.456 p < 0.015, with the baseline PI 0.417, p < 0.007, with the baseline IR, p < 0.007, with the difference between the final and baseline AD 0.295, p < 0.061, with the difference between the final and baseline PI –0.345, p < 0.027 and with the difference between the final and baseline RI < –0.472, p < 0.002 (Tables 4 and 5).

Table 4

Correlation analysis between the neutrophil lymphocyte ratio and the platelet lymphocyte ratio with vasomotor symptoms and laboratory variables

VariablePremenopausal (n = 41)Postmenopausal (n = 41)
NLRpPLRpNLRpPLRp
How many VMS a day–0.0220.9100.1080.569–0.2500.200–0.4560.015
Cholesterol (mg/dl)0.3030.0570.1680.2990.0460.7770.2730.084
Triglycerides (mg/dl)0.376*0.0170.0750.6460.1050.5130.0900.576

[i] Results represent Sperman’s correlation coefficient and p values. VMS – vasomotor symptoms, NLR – neutrophil/lymphocyte index, PLR – platelet/lymphocyte ratio

Table 5

Correlation analysis between the neutrophil/lymphocyte ratio, the platelet/lymphocyte ratio and Doppler parameters of brachial artery in pre- and postmenopausal women

VariablePremenopausalPostmenopausal
NLRpPLRpNLRpPLRP
Baseline artery diameter0.2760.0800.3520.024–0.2360.137–0.0890.581
Baseline pulsatility index0.0370.8170.2730.0840.1550.3330.4170.007
Baseline resistance index0.0610.7030.3150.0450.3360.0320.4170.007
Baseline resistance index post hyperemic stimulus0.0170.9170.3940.0110.1230.4420.1000.532
Final arterial diameter minus baseline arterial diameter–0.1820.254–0.0540.7380.2230.1610.2950.061
Final pulsatility index minus baseline pulsatility index–0.0730.651–0.1020.525–0.2060.196–0.3450.027
Final resistance index minus baseline resistance index–0.0200.9010.1450.366–0.3710.017–0.4720.002

[i] Results represent Sperman’s correlation coefficient and p values. NLR – neutrophil/lymphocyte index, PLR – platelet/lymphocyte ratio

In the correlation analysis once the group was divided into pre- and postmenopausal patients with presence or absence of VMS, the following was found: in premenopausal women without VMS, the NLR correlated with cholesterol levels 0.745, p < 0.013, the PLR correlated with the BMI 0.697, p < 0.025. In the postmenopausal group without VMS, the PLR correlated with cholesterol levels, 0.599 p < 0.031. In the premenopausal group with VMS the NLR correlated with the WHR 0.374, p < 0.05, in the postmenopausal with hot flashes the PLR correlated with the HDL-C 0.384, p < 0.033. In the other cardiovascular risk parameters, it was found in the premenopausal group without VMS, a correlation of the PLR with the 0.610 IR, p < 0.061 and with a post-hyperemic stimulus RI 0.817, p < 0.004. In the premenopausal group without VMS there was a correlation between the NLR and the SF/VF –0.549 ratio, p < 0.052. In the premenopausal group with VMS there was a correlation between the PLR and the baseline arterial diameter 0.387, p < 0.032 and in the postmenopausal group there was a correlation between the PLR and the IMT –0.425 p < 0.024 (Tables 6 and 7).

Table 6

Correlation analysis between the neutrophil/lymphocyte ratio and platelet/lymphocyte ratio with anthropometric and laboratory parameters in pre- and postmenopausal women, further divided by the presence or absence of vasomotor symptoms

ParameterNLRpPLRpNLRpPLRpNLRpPLRpNLRpPLRp
VMS no
n = 10
VMS noVMS no
n = 13
VMS no
n = 13
VMS yes
n = 31
VMS yesVMS yes
n = 28
VMS yes
PremenopausalPremenopausalPostemenopausalPostemenopausal
Body mass index0.1640.6510.6970.025–0.0710.8170.0710.8170.0110.954–0.1310.4810.0450.8210.0090.964
Cholesterol0.7450.0130.2970.4050.2310.4480.5990.0310.2030.2820.1170.538–0.0070.9710.2200.260

[i] Results represent Sperman’s correlation coefficient and p values. VMS – vasomotor symptoms, NLR – neutrophil/lymphocyte index, PLR – platelet/lymphocyte ratio

Table 7

Correlation analysis between the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and intima-media thickness, subcutaneous fat/viscera fat ratio and brachial artery Doppler parameters in pre- and postmenopausal women, further divided by the presence or absence of vasomotor symptoms

ParameterNLR
n = 10
pPLR
n = 10
pNLR
n = 13
pPLR
n = 13
pNLR
n = 31
pPLR
n = 31
pNLR
n = 28
pPLR
n =28
p
PostmenopausalPremenopausalPremenopausalPremenopausal
Intima-media thickness–0.0180.960–0.3780.2810.1300.6720.1660.587–0.0660.7250.0820.662–0.2490.201–0.4250.024
SF/VF0.2480.4890.1270.726–0.5490.052–0.4620.1120.0490.7940.1000.5920.2680.1680.2680.168
Baseline artery diameter0.3280.3540.1160.751–0.1050.734–0.4370.1350.2810.1260.3870.032–0.2740.1580.0760.700
Baseline resistance Index0.1400.6990.6100.0610.3910.1870.4790.0980.1000.5920.2050.2680.2890.1360.3560.063
Pulsatility index post hyperemic stimulus–0.1340.7120.8170.004–0.2310.4480.0710.817–0.0420.8230.1340.4730.1170.5520.1310.506
Resistance index post hyperemic stimulus–0.1700.6380.5780.080–0.2040.5050.0770.8020.1070.5650.3810.0350.2280.2440.0250.900
Final arterial diameter minus baseline arterial diameter–0.2070.5670.2980.403–0.1860.5440.4760.100–0.1620.384–0.1220.5130.4060.0320.1820.354
Final pulsatility index minus baseline pulsatility index–0.1340.713–0.0790.828–0.7200.006–0.3900.188–0.0780.677–0.0980.5990.0220.910–0.3120.106
Final resistance index minus baseline resistance index–0.2550.476–0.1030.776–0.6430.018–0.5660.0440.0510.7840.2590.160–0.2540.192–0.4280.023

[i] SF – subcutaneous fat, VF – visceral fat

Discussion

Inflammation has been involved in various processes including atherosclerosis. After menopause an increase in cardiovascular events is more frequent [3, 4], most likely due to a decrease in estradiol concentrations that have an anti-inflammatory effect [6].

The NLR, a marker of inflammation, has allowed the prediction of cardiovascular complications [10]. That is why in this study it was intended to observe if there was any difference in this ratio between pre- and postmenopausal women and to determine its relationship with other cardiovascular risk markers such as fat visceral, epicardial fat and endothelial function, however this study found no differences in NLR and PLR between pre- and postmenopausal women, nor after having been divided based on the presence or not of vasomotor symptoms.

In premenopausal women, the positive correlation between the NLR with cholesterol and triglycerides may indicate an increased risk of atherosclerosis as it is an inflammatory process [43].

The correlation of the PLR with the baseline AD, with baseline RI and with post-hyperemic stimulus RI indicates the relation of inflammation with these parameters.

In the postmenopausal patients there was a positive correlation of the NLR with the baseline RI and negative with the difference between final and baseline hyperemic stimulus RI, for which we have no explanation. There was a negative correlation between the PLR and the number of VMS per day, and positive with the baseline PI, with the baseline RI, with the difference between final and baseline AD and the negative DAB, as well as with the difference between final and baseline PI final PI and the baseline PI and negative with the difference between final and baseline IR. In the first case, having less VMS, less inflammation is associated with lower cardiovascular risk, as has already been reported [44, 45].

In premenopausal women without hot flashes, the NLR correlated positively with cholesterol and the PLR positively correlated with the BMI.

In the postmenopausal group without hot flashes, the PLR correlated positively with cholesterol, with a greater cardiovascular risk associated with inflammation and dyslipidemia [43].

In the premenopausal group with hot flashes, the NLR positively correlated with the WHR, which implies that upper level fat distribution is associated with greater inflammation and greater cardiovascular risk [20].

In postmenopausal women with hot flashes, the PLR positively correlated with HDL-C levels for which we have no explanation.

In the premenopausal group without VMS, there was a correlation between PLR and RI and with post hyperemic stimuls RI this means that hot flashes influence inflammation, and vascular resistance [45].

In the premenopausal group without VMS, there was a negative correlation of the NLR with the SF/VF ratio, which means that the inflammation is lower to greater parietal fat [20, 23, 35, 46]. Although other studies have found a greater inflammatory effect of parietal fat [47].

In the group of premenopausal patients with VMS, there was a positive correlation between the PLR and baseline arterial diameter, which indicates that women with hot flashes have greater inflammation that affects the vascular endothelium [9, 40-42, 48, 49].

In the postmenopausal group there was a negative correlation between the PLR and the IMT, which shows a greater risk of atherosclerosis with lower inflamation for which we have no explanation.

The limitation of this study was sample size since after division of the main group in subgroups no statistical differences were found, so it is needed a greater sample size to really determine if it can be used as a clinical aid. So it is possible to conclude that inflammation is related with other cardiovascular risk markers, NLR was not different between premenopausal and postmenopausal women but abnormal PLR was greater in those postmenopausal with vasomotor symptoms.

Disclosure

The authors report no conflict of interest.

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Carranza-Lira Ş. Climaterio. In: Introducción a la endocrinología ginecológica. 1a ed. Trillas, Mexico 2011: 121-134.

2 

Mankad RBest PJM. Cardiovascular disease in older women: a challenge in diagnosis and treatment. Womens Health (Lond Engl) 2008; 4: 449-464.

3 

Clark P. Epidemiología e impacto de la enfermedad cardiovascular en la mujer posmenopáusica. In: Temas selectos en climaterio, Carranza-Lira S (ed.). 1a ed. Alfil SA de CV, México 2016: 1-12.

4 

Secretaría de Salud. Prontuario de la Salud 2015: 127. https://www.gob.mx/salud/documentos/prontuario-de-la-salud?state=published

5 

Carranza-Lira Ş. Terapia hormonal de reemplazo: riesgos y beneficios cardiovasculares. In: Temas selectos en climaterio, Carranza-Lira S (ed.). 1a ed. Alfil SA de CV, México 2016: 91-100.

6 

Santos RSDe Fatima LAFrank APet al.. The effects of 17 alpha-estradiol to inhibit inflammation in vitro. Biol Sex Differ 2017; 8: 1-13.

7 

Rossouw JEPrentice RLManson JEet al.. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. J Am Med Assoc 2007; 297: 1465-1477.

8 

Viola JSoehnlein O. Atherosclerosis–a matter of unresolved inflammation. Semin Immunol 2015; 27: 184-193.

9 

Sites CKToth MJCushman Met al.. Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. Fertil Steril 2002; 77: 128-135.

10 

Azab BChainani VShah NMcGinn JT. Neutrophil-lymphocyte ratio as a predictor of major adverse cardiac events among diabetic population: A 4-year follow-up study. Angiology 2013; 64: 456-465.

11 

DiGangi C. Neutrophil-lymphocyte ratio: Predicting cardiovascular and renal complications in patients with diabetes. J Am Assoc Nurse Pract 2016; 28: 410-414.

12 

Li HLu XXiong RWang S. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators Inflamm 2017; 2017: 9327136.

13 

Belen ESungur ASungur MAErdoğan G. increased neutrophil to lymphocyte ratio in patients with resistant hypertension. J Clin Hypertens (Greenwich) 2015; 17: 532-537.

14 

Martínez-Urbistondo DBeltrán ABeloqui OHuerta A. El índice neutrófilo/linfocito como marcador de disfunción sistémica endotelial en sujetos asintomáticos. Nefrología 2016; 36: 397-403.

15 

Li HHorke SFörstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014; 237: 208-219.

16 

Förstermann UXia NLi H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circulation Research 2017; 120: 713-735.

17 

Luckie DACortés VFIbarra MS. Obesidad: trascendencia y repercusión médico-social. Revista de Especialidades Médico-Quirúrgicas 2009; 14: 191-201.

18 

Eshtiaghi REsteghamati ANakhjavani M. Menopause is an independent predictor of metabolic syndrome in Iranian women. Maturitas 2010; 65: 262-266.

19 

Farhangi MAKeshavarz SAEshraghian Met al.. White blood cell count in women: Relation to inflammatory biomarkers, haematological profiles, visceral adiposity, and other cardiovascular risk factors. J Heal Popul Nutr 2013; 31: 58-64.

20 

Chiba YSaitoh STagaki Set al.. Relationship between viceral fat and cardiovascular disease risk factors: The Tanno and Sobetsu study. Hypertens Res 2007; 30: 229-236.

21 

Zamboni MArmellini FTurcato Eet al.. Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese women. J Intern Med 1994; 236: 521-527.

22 

Anderson PJChan JCChan YLet al.. Visceral fat and cardiovascular risk factors in Chinese NIDDM patients. Diabetes Care 1997; 20: 1854-1958.

23 

Magnuson AMFouts JKRegan DPet al.. Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node. Physiol Behav 2018; 190: 71-81.

24 

Carranza-Lira SAzpilcueta YMMOrtiz SR. Relation between visceral fat and carotid intimal media thickness in Mexican postmenopausal women: A preliminary report. Prz Menopauzalny 2016; 15: 81-84.

25 

Jarpa CPineda VManterola C. Grosor de la íntima-media carotídea como predictor de evento cardiovascular. Revisión sistemática de la literatura. Int J Morphol 2013; 31: 293-300.

26 

Coll BFeinstein SB. Carotid intima-media thickness measurements: techniques and clinical relevance. Curr Atheroscler Rep 2008; 10: 444-450.

27 

Farouque HMMeredith IT. The assessment of endothelial function in humans. Coron Artery Dis 2001; 12: 445-454.

28 

Moens ALGoovaerts IClaeys MJVrints CJ. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 2005; 127: 2254-2263.

29 

Takase BUehata AAkima Tet al.. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 1998; 82: 1535-1539.

30 

Carranza-Lira SMuro AMFOrtiz SR. Relation of skinfold thickness and visceral fat with the endothelial function in Mexican postmenopausal women. Prz Menopauzalny 2015; 14: 90-96.

31 

López-Jiménez FSochor O. Epicardial fat, metabolic dysregulation, and cardiovascular risk: Putting things together. Rev Esp Cardiol 2014; 67: 425-427.

32 

Fernández Muñoz MJBasurto Acevedo LCórdova Pérez Net al.. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women. Rev Española Cardiol 2014; 67: 436-441.

33 

Sahbaz ACicekler HAynioglu Oet al.. Comparison of the predictive value of plateletcrit with various other blood parameters in gestational diabetes development. J Obstet Gynaecol (Lahore) 2016; 36: 589-593.

34 

Carranza-Lira SBárcena-Jacobo TDSandoval-Barragán MPRamos-León JC. Visceral adiposity after tibolone use. Int J Gynecol Obstet 2011; 115: 191-193.

35 

Almeida E dos PSabino Pinho CPLeão APDet al.. Razón entre grasa visceral y subcutánea como predictor de alteraciones cardiometabólicas. Rev Chil Nutr 2018; 45: 28-36.

36 

Iacobellis GAssael FRibaudo MCet al.. Epicardial fat from echocardiography: A new method for visceral adipose tissue prediction. Obes Res 2003; 11: 304-310.

37 

Lima-Martínez MMBalladares NTorres Cet al.. Medición ecocardiográfica de la grasa epicárdica. Imagen Diagnostica 2011; 2: 23-26.

38 

Lima-Martínez MMPaoli MDonis JHet al.. Punto de corte de espesor de tejido adiposo epicárdico para predecir síndrome metabólico en población venezolana. Endocrinol Nutr 2013; 60: 570-576.

39 

Cabrera-Rego JONavarro-Despaigne DStaroushik-Morel Let al.. Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause. Clin Investig Arterioscler 2018; 30: 21-27.

40 

Rubio-Guerra AFGuerrero-García CMeneses-Acero Iet al.. Epicardial fat thickness, but not intraabdominal fat, correlates with intima-media thickness in patients with metabolic syndrome. Obes Res Clin Pract 2019; 13: 602-603.

41 

Carranza-Lira SCuan-Martínez JRRosales-Ortíz S. Brachial artery responses in menopausal women using tibolone. Int J Gynaecol Obstet 2008; 101: 43-46.

42 

Carranza-Lira SCirigo-Hernández BSandoval-Barragán MPRamos-León JC. Comparison of brachial artery vascular responses among postmenopausal women receiving different doses of tibolone. Int J Gynecol Obstet 2013; 122: 75-77.

43 

Chung SParks JS. Dietary cholesterol effects on adipose tissue inflammation. Curr Opin Lipidol 2016; 27: 19-25.

44 

Biglia NCagnacci AGambacciani Met al.. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017; 20: 306-312.

45 

Bechlioulis ANaka KKKalantaridou SNet al.. Increased vascular inflammation in early menopausal women is associated with hot flush severity. J Clin Endocrinol Metab 2012; 97: 760-764.

46 

Izaola Ode Luis DSajoux Iet al.. Inflamación y obesidad (Lipoinflamación). Nutr Hosp 2015; 31: 2352-2358.

47 

Lesna IKCejkova SKralova Aet al.. Human adipose tissue accumulation is associated with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue. Nutr Diabetes 2017; 7: e264.

48 

Huang AJSawaya GFVittinghoff Eet al.. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women. Menopause 2018; 25: 1286-1290.

49 

Gordon JLRubinow DRThurston RCet al.. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause 2016; 23: 1189-1198.

1. Carranza-Lira Ş. Climaterio. In: Introducción a la endocrinología ginecológica. 1a ed. Trillas, Mexico 2011: 121-134.
2. Mankad R, Best PJM. Cardiovascular disease in older women: a challenge in diagnosis and treatment. Womens Health (Lond Engl) 2008; 4: 449-464.
3. Clark P. Epidemiología e impacto de la enfermedad cardiovascular en la mujer posmenopáusica. In: Temas selectos en climaterio, Carranza-Lira S (ed.). 1a ed. Alfil SA de CV, México 2016: 1-12.
4. Secretaría de Salud. Prontuario de la Salud 2015: 127. https://www.gob.mx/salud/documentos/prontuario-de-la-salud?state=published
5. Carranza-Lira Ş. Terapia hormonal de reemplazo: riesgos y beneficios cardiovasculares. In: Temas selectos en climaterio, Carranza-Lira S (ed.). 1a ed. Alfil SA de CV, México 2016: 91-100.
6. Santos RS, De Fatima LA, Frank AP, et al. The effects of 17 alpha-estradiol to inhibit inflammation in vitro. Biol Sex Differ 2017; 8: 1-13.
7. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. J Am Med Assoc 2007; 297: 1465-1477.
8. Viola J, Soehnlein O. Atherosclerosis – a matter of unresolved inflammation. Semin Immunol 2015; 27: 184-193.
9. Sites CK, Toth MJ, Cushman M, et al. Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. Fertil Steril 2002; 77: 128-135.
10. Azab B, Chainani V, Shah N, McGinn JT. Neutrophil-lymphocyte ratio as a predictor of major adverse cardiac events among diabetic population: A 4-year follow-up study. Angiology 2013; 64: 456-465.
11. DiGangi C. Neutrophil-lymphocyte ratio: Predicting cardiovascular and renal complications in patients with diabetes. J Am Assoc Nurse Pract 2016; 28: 410-414.
12. Li H, Lu X, Xiong R, Wang S. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators Inflamm 2017; 2017: 9327136.
13. Belen E, Sungur A, Sungur MA, Erdoğan G. increased neutrophil to lymphocyte ratio in patients with resistant hypertension. J Clin Hypertens (Greenwich) 2015; 17: 532-537.
14. Martínez-Urbistondo D, Beltrán A, Beloqui O, Huerta A. El índice neutrófilo/linfocito como marcador de disfunción sistémica endotelial en sujetos asintomáticos. Nefrología 2016; 36: 397-403.
15. Li H, Horke S, Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014; 237: 208-219.
16. Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circulation Research 2017; 120: 713-735.
17. Luckie DA, Cortés VF, Ibarra MS. Obesidad: trascendencia y repercusión médico-social. Revista de Especialidades Médico-Quirúrgicas 2009; 14: 191-201.
18. Eshtiaghi R, Esteghamati A, Nakhjavani M. Menopause is an independent predictor of metabolic syndrome in Iranian women. Maturitas 2010; 65: 262-266.
19. Farhangi MA, Keshavarz SA, Eshraghian M, et al. White blood cell count in women: Relation to inflammatory biomarkers, haematological profiles, visceral adiposity, and other cardiovascular risk factors. J Heal Popul Nutr 2013; 31: 58-64.
20. Chiba Y, Saitoh S, Tagaki S, et al. Relationship between viceral fat and cardiovascular disease risk factors: The Tanno and Sobetsu study. Hypertens Res 2007; 30: 229-236.
21. Zamboni M, Armellini F, Turcato E, et al. Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese women. J Intern Med 1994; 236: 521-527.
22. Anderson PJ, Chan JC, Chan YL, et al. Visceral fat and cardiovascular risk factors in Chinese NIDDM patients. Diabetes Care 1997; 20: 1854-1958.
23. Magnuson AM, Fouts JK, Regan DP, et al. Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node. Physiol Behav 2018; 190: 71-81.
24. Carranza-Lira S, Azpilcueta YMM, Ortiz SR. Relation between visceral fat and carotid intimal media thickness in Mexican postmenopausal women: A preliminary report. Prz Menopauzalny 2016; 15: 81-84.
25. Jarpa C, Pineda V, Manterola C. Grosor de la íntima-media carotídea como predictor de evento cardiovascular. Revisión sistemática de la literatura. Int J Morphol 2013; 31: 293-300.
26. Coll B, Feinstein SB. Carotid intima-media thickness measurements: techniques and clinical relevance. Curr Atheroscler Rep 2008; 10: 444-450.
27. Farouque HM, Meredith IT. The assessment of endothelial function in humans. Coron Artery Dis 2001; 12: 445-454.
28. Moens AL, Goovaerts I, Claeys MJ, Vrints CJ. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 2005; 127: 2254-2263.
29. Takase B, Uehata A, Akima T, et al. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 1998; 82: 1535-1539.
30. Carranza-Lira S, Muro AMF, Ortiz SR. Relation of skinfold thickness and visceral fat with the endothelial function in Mexican postmenopausal women. Prz Menopauzalny 2015; 14: 90-96.
31. López-Jiménez F, Sochor O. Epicardial fat, metabolic dysregulation, and cardiovascular risk: Putting things together. Rev Esp Cardiol 2014; 67: 425-427.
32. Fernández Muñoz MJ, Basurto Acevedo L, Córdova Pérez N, et al. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women. Rev Española Cardiol 2014; 67: 436-441.
33. Sahbaz A, Cicekler H, Aynioglu O, et al. Comparison of the predictive value of plateletcrit with various other blood parameters in gestational diabetes development. J Obstet Gynaecol (Lahore) 2016; 36: 589-593.
34. Carranza-Lira S, Bárcena-Jacobo TD, Sandoval-Barragán MP, Ramos-León JC. Visceral adiposity after tibolone use. Int J Gynecol Obstet 2011; 115: 191-193.
35. Almeida E dos P, Sabino Pinho CP, Leão APD, et al. Razón entre grasa visceral y subcutánea como predictor de alteraciones cardiometabólicas. Rev Chil Nutr 2018; 45: 28-36.
36. Iacobellis G, Assael F, Ribaudo MC, et al. Epicardial fat from echocardiography: A new method for visceral adipose tissue prediction. Obes Res 2003; 11: 304-310.
37. Lima-Martínez MM, Balladares N, Torres C, et al. Medición ecocardiográfica de la grasa epicárdica. Imagen Diagnostica 2011; 2: 23-26.
38. Lima-Martínez MM, Paoli M, Donis JH, et al. Punto de corte de espesor de tejido adiposo epicárdico para predecir síndrome metabólico en población venezolana. Endocrinol Nutr 2013; 60: 570-576.
39. Cabrera-Rego JO, Navarro-Despaigne D, Staroushik-Morel L, et al. Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause. Clin Investig Arterioscler 2018; 30: 21-27.
40. Rubio-Guerra AF, Guerrero-García C, Meneses-Acero I, et al. Epicardial fat thickness, but not intraabdominal fat, correlates with intima-media thickness in patients with metabolic syndrome. Obes Res Clin Pract 2019; 13: 602-603.
41. Carranza-Lira S, Cuan-Martínez JR, Rosales-Ortíz S. Brachial artery responses in menopausal women using tibolone. Int J Gynaecol Obstet 2008; 101: 43-46.
42. Carranza-Lira S, Cirigo-Hernández B, Sandoval-Barragán MP, Ramos-León JC. Comparison of brachial artery vascular responses among postmenopausal women receiving different doses of tibolone. Int J Gynecol Obstet 2013; 122: 75-77.
43. Chung S, Parks JS. Dietary cholesterol effects on adipose tissue inflammation. Curr Opin Lipidol 2016; 27: 19-25.
44. Biglia N, Cagnacci A, Gambacciani M, et al. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017; 20: 306-312.
45. Bechlioulis A, Naka KK, Kalantaridou SN, et al. Increased vascular inflammation in early menopausal women is associated with hot flush severity. J Clin Endocrinol Metab 2012; 97: 760-764.
46. Izaola O, de Luis D, Sajoux I, et al. Inflamación y obesidad (Lipoinflamación). Nutr Hosp 2015; 31: 2352-2358.
47. Lesna IK, Cejkova S, Kralova A, et al. Human adipose tissue accumulation is associated with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue. Nutr Diabetes 2017; 7: e264.
48. Huang AJ, Sawaya GF, Vittinghoff E, et al. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women. Menopause 2018; 25: 1286-1290.
49. Gordon JL, Rubinow DR, Thurston RC, et al. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause 2016; 23: 1189-1198.
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