The correlation between atherogenic indexes and erectile dysfunction

Abstract

Aside from the ordinary plasma lipid level measurements, the ratios based on individual plasma lipid levels such as atherogenic index of plasma (AIP), Castelli’s risk index 1/2 (CRI-1/2), and atherogenic coefficient (AC) are the novel parameters to evaluate the patients with a high risk of CVD. In this study, we aim to evaluate the relationship between AIP, AC, and CRI-1/2 with increased risk of ED. Between April 2018 and February 2019, 253 patients, who were diagnosed as a vasculogenic ED in our clinic, were enrolled in the study. While the first group (n = 134) consisted of patients with moderate and mild ED (IIEF-EF: 17–30), the second group (n = 119) consisted of patients with severe ED. In addition to the mean values of lipid parameters; CRI-1 (total cholesterol/HDL), CRI-2 (LDL/HDL) AIP (log10(triglycerides/HDL), and AC (non-HDL/HDL) were calculated. The mean age was 44.02 ± 10.41 (24–70), and the mean BMI was 27.80 ± 4.12 (18.52 ± 41.97). However, CRI-1 and AIP values were found to be higher in the severe ED group compared to the mild ED group (CRI-1: 4.50 ± 1.47, 4.88 ± 1.30; p = .039; AIP: 0.489 ± 0.315, 0.617 ± 0.283; p = .007). Our results demonstrated that CR-1 and AIP have a positive correlation with the severity of ED. Moreover, we can suggest that patients with higher CR-1 and AIP values are likely to have more severe ED in the future.

Keywords:

• Atherosclerosis
• atherogenic index
• Castelli’s risk index
• erectile dysfunction

Introduction

Erectile dysfunction (ED) is described as the incapability to get or keep an erection firm enough for satisfactory sexual intercourse [1]. Its prevalence is about 52% among the men between the ages of 40 and 70 years [2,3]. Although ED occurs due to multifactorial reasons, usually underlying pathology is the endothelial dysfunction [4]. Since the atheroma plaques form and endothelial dysfunction begins in capillaries first, the presence of ED is suggested as an early warning of cardiovascular diseases (CVDs) [5,6]. Furthermore, many studies proved that the ED and CVD have a common pathophysiological basis as vascular insufficiency [7,8]. In a preclinical study, Azadzoi et al. [9] reported that atherosclerotic rabbits had a higher chance of developing ED than non-atherosclerotic rabbits. Moreover, Montorsi et al. [10] reported that ED prevalence was higher in CVD sufferers than the healthy population (65% vs. 22%).

According to literature, the most accepted risk factor for CVD is dyslipidemia, which is a disorder of lipoprotein metabolism. Therefore, high levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs) have been recommended as useful tools to predict the risk of CVD [11]. Moreover, due to the close pathophysiological relation of CVD and ED, these biomarkers have also been used by clinicians to predict ED [12,13]. However, according to latest studies, the ratios based on individual plasma lipid levels such as atherogenic index of plasma (AIP), Castelli’s risk index 1/2 (CRI-1/2), and atherogenic coefficient (AC) are indicated as more reliable predictors of CVD related events than the conventional lipid measurements [14]. Due to their possible relevance, in this study, we aim to evaluate the relationship between increased values of AIP, AC, and CRI-1/2 with increased risk of ED.

Materials and methods

We designed a cross-sectional observational study. Between April 2018 and February 2019, 253 patients, who were diagnosed as a vasculogenic ED in our clinic, were enrolled in the study. The present study protocol was reviewed and approved by the Institutional Review Board of Okmeydani Training & Research Hospital (approval no. 892/2018). Informed consent was obtained by all subjects when they were enrolled.

We used the validated Turkish version of the International Index of Erectile Dysfunction (IIEF-EF) to separate the patients into the two groups [15]. We used IIEF-EF because it is a highly reliable and validated scoring system to evaluate the severity of ED [16]. While the first group (n = 134) consisted of patients with moderate and mild ED (IIEF-EF: 17–25), the second group (n = 119) consisted of patients with severe ED (IIEF-EF < 17). According to previous study about cut-off value of IIEF, no ED (EF score 26–30), mild (EF score 22–25), mild to moderate (EF score 17–21), moderate (EF score 11–16), and severe (EF score 6–10) [17]. The etiology of ED was determined by the medical history and physical examination and biochemical test results of the patients. We questioned the nocturnal erections and tumescence during masturbation so as to exclude psychogenic ED. Furthermore, patients with a rapid onset of ED were also considered as psychogenic ED and excluded from the study.

A health history questionnaire was filled out by all patients, and a detailed physical examination was performed. All of the patients were questioned for drug history, such as antidepressant, antipsychotic, and antiarrhythmic drug usage. Each patient’s drinking alcohol and smoking habits were recorded. Body mass index (BMI) of patients were calculated. All patients were consulted with the cardiology department in order to exclude the patients with CVD. The patients who had neurological diseases were also excluded. Furthermore, patients with a history of a penile surgery or any penile deformity were excluded from the study. Total testosterone, sex hormone-binding globulin (SHBG), and albumin levels were measured in order to exclude hypogonadism. In addition, fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), TGs, TC, luteinizing hormone (LH), and follicular stimulating hormone (FSH) levels were also measured. Moreover, the mean values of lipid parameters; CRI-1 (TC/HDL), CRI-2 (LDL/HDL) AIP (log10(TGs/HDL), and AC (non-HDL/HDL) were calculated.

Statistical analysis

SPSS 23.0 software was used for data analyses (SPSS, Version 23.0; IBM Corp, Armonk, NY). To determine the distribution, the Kolmogorov–Smirnov normality test was performed. Afterward, the Student t-test was used to compare the groups, and the results were reported as the mean and the standard deviation (±SD). The analysis of variance (ANOVA) was used to make statistical comparisons. Pearson’s and Spearman’s correlation was used for numerical and nominal data, respectively. The statistical significance was set at p < .05.

Results

The mean age was 44.02 ± 10.41 (24-70) years, and the mean BMI was 27.80 ± 4.12 kg/m² (18.52 ± 41.97). The mean IIEF-EF score was 16.99 ± 7.59 (0–30). The demographic data of patients are demonstrated in Table 1. No statistically significant difference was observed between groups regarding age, BMI, TC, testosterone, FSH, and LH levels. However, CRI-1 and AIP values were found to be higher in the severe ED group compared to the mild ED group (CRI-1: 4.50 ± 1.47, 4.88 ± 1.30; p = .039; AIP: 0.489 ± 0.315, 0.617 ± 0.283; p = .007). The comparison between groups is shown in Table 2. We also evaluate the correlation between the atherogenic indexes and the severity of ED (Table 3). Therefore, we did Spearman’s correlation analysis and found that all indexes and IIEF-EF scores have a negative correlation; however, only CRI-1 and AIP were found statistically significant (CRI-1: −0.327, p = .027, AIP: –0.433, p = .002).

Table 1. Demographic characteristics of patients.

n = 253	Mean + SD	Min–Max
Age	44.02 ± 10.41	24–70
BMI	27.80 ± 4.12	18.52 ± 41.97
Smoking status (no/yes)	140/113
Alcohol status (no/yes)	230/23
DM (no/yes)	214/39
HT (no/yes)	208/45
CAD (no/yes)	241/12
IIEF-EF score	16.99 ± 7.59	0–30
LDL	117.21 ± 34.20	29–300
HDL	44.31 ± 11.18	21–95
Triglycerides	152.81 ± 96.31	40–844
Total cholesterol	188.85 ± 34.52	111–284
FSH	6.75 ± 3.65	2.18–18.66
LH	5.38 ± 2.60	1.33–14.12
Total testosterone	4.10 ± 1.61	1.02–10.25

Table 2. Comparison between groups.

	Mild–moderate group (n = 134)	Severe group (n = 119)	p Value
Age	47.61 ± 10.71	49.32 ± 10.15	.201
BMI	27.69 ± 4.12	27.99 ± 4.11	.566
Smoking status (no/yes)	65	48	.509
Alcohol status (no/yes)	16	7	.147
DM (no/yes)	19	20	.091
HT (no/yes)	20	25	.101
CAD (no/yes)	6	6	.696
IIEF-EF score	22.41 ± 4.3	10.54 ± 5.23	<.001
LDL	114.78 ± 31.72	120.10 ± 36.94	.329
HDL	44.92 ± 12.37	43.57 ± 9.62	.442
Triglycerides	182.43 ± 87.32	190.79 ± 107.69	.062
Total cholesterol	198.34 ± 35.48	202.44 ± 41.23	.071
FSH	6.16 ± 2.92	6.91 ± 3.83	.535
LH	5.55 ± 2.77	5.33 ± 2.58	.811
Total testosterone	4.18 ± 1.65	3.99 ± 1.55	.437
Castelli's risk index-1	4.51 ± 1.49	5.11 ± 1.57	.013
Castelli's risk index-2	2.64 ± 1.12	2.78 ± 1.16	.258
Atherogenic coefficient	3.51 ± 1.49	4.11 ± 1.57	.131
Atherogenic index of plasma	0.49 ± 0.31	0.60 ± 0.24	.007

Table 3. Correlation between atherogenic indexes and erectile function scores.

	IIEF score
	r	p Value
Castelli's risk index-1	–0.327	.027
Castelli's risk index-2	–0.059	.456
Atherogenic coefficient	–0.172	.271
Atherogenic index of plasma	–0.433	.002

Discussion

In our study, we proved that higher values of CRI-1 and AIP are directly correlated with the severity of ED. Therefore, we suggest that CRI-1 and AIP can be useful tools to predict ED risk in patients with CVD.

According to epidemiological studies, arteriogenic form of vasculogenic ED is the most common form of ED [18]. Besides, the underlying pathology of the vasculogenic ED is atherosclerosis, like CVD. However, penile arteries are prone to be affected by atherosclerosis before the coronary arteries due to their small diameters [12,19]. Studies support this finding by proving that ED is seen in approximately 50% in patients with CAD [20]. Therefore, ED can be used to predict early cardiovascular events such as myocardial infarction, even before any systemic disease was developed. Moreover, from the first symptoms of ED to the development of CVD symptoms, there are two to three years, which is enough time to take action [21]. Due to the high importance of the subject, ED has been studied as a potential indicator of dyslipidemia and related pathologies by many studies [22]. Total oxidant/antioxidant capacity, reactive oxygen metabolites, hydroperoxides, and lipoprotein-associated phospholipase A2 levels have been already evaluated in ED patients [12,23–25]. However, atherogenic indexes and ED correlation were not evaluated before in the literature.

Previous studies indicated that some lipid biomarkers were more crucial than the others. For example, Sood et al. [26] reported that FBS, TG, and waist circumference were significantly affecting the erectile functions, whereas Sanjay et al. [27] suggested that HDL, TG, and FBS were the most crucial biomarkers for the erectile functions. However, in recent studies, atherogenic biomarker ratios such as CRI-1/2 have suggested more sensitive predictors of CVD than traditional lipid biomarkers [28]. In Framingham Study, Kannel [29] reported that the specific ratios of plasma lipid levels were significantly more powerful predictors of CVD than the plasma levels of HDL-C or LDL-C. Furthermore, the Helsinki Hearth Study indicated clearly that the CRI-2 values could predict CVD risks better than LDL-C or HDL-C levels [30]. In our study, we found that CRI-1 and IIEF-EF scores had a statistically significant negative correlation. The studies reported that the CRI-1 ratio is calculated by dividing TC by HDL-C [31]. Therefore, we can suggest that higher CRI-1 values indicate a high level of TC or low level of HDL-C or both. Moreover, a low score of IIEF-EF indicates severe ED. Thus, our result supports the usage of CRI-1 as a novel risk determination tool for ED.

Another lipid ratio, which is called AIP, was also suggested as a strong predictor of CVD [32]. Values above 0.24 have been shown to be associated with high cardiovascular risk [33]. Uslu et al. [34] reported that patients with higher AIP values had increased thickness of carotid intima-media. According to this study, AIP values can be suggested as a predictor of subclinical atherosclerosis. Furthermore, Ermis et al. [35] evaluated AIP values in ED patients. Values were found statistically significant different between mild and severe ED patients. Therefore, AIP can be suggested as a useful marker to determine the severity of ED alongside with severity of atherosclerosis.

According to our findings, there was no correlation between CR-2 and AC with the severity of ED. However, our results demonstrated that CR-1 and AIP have a positive correlation with the severity of ED. These results indicated that patients with higher CR-1 and AIP values are likely to have more severe ED in the future. Moreover, our results are supported by previous studies [15,16].

However, we have a limitation that needs to be addressed. We defined the severity of ED based on the IIEF-EF score instead of penile artery ultrasound or other objective methods. Penile Doppler ultrasound might be useful for a more objective result. However, due to difficulties of the practice in the procedure, it was not convenient in our clinic.

Conclusions

The present findings of this study suggest that atherogenic indexes may be a useful tool to predict the severity of ED in atherosclerotic patients. Especially, CRI-1 and AIP have high potential in urological practice. Nevertheless, we need more detailed prospective randomized studies to investigate the true nature of these indexes.

Notes on contributors

Conceptualization: MGC, LC. Data curation: HAA, EM. Formal analysis: MGC, AA. Investigation: MGC, RBD. Methodology: MGC, HAA. Project administration: RBD, FA. Resources: ATA, EM. Supervision: AA, FA. Writing – original draft: ATA, MGC. Writing – review and editing: MGC, LC.

Acknowledgements

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

The work was performed at the Urology Department of Okmeydani Training and Research Hospital Istanbul, Turkey.

Disclosure statement

All authors declare that he/she has no conflict of interest.