29 May 2014: Clinical Research
Carotid artery intima-media thickness and erectile dysfunction in patients with metabolic syndrome
Mustafa Unal D , Duygu Yazgan Aksoy B , Yusuf Aydın C , Mine Durusu Tanriover E , Dilek Berker F , Jale Karakaya C , Serdar Guler G
DOI: 10.12659/MSM.889771
Med Sci Monit 2014; 20:884-888
Abstract
BACKGROUND: Metabolic syndrome (MS) has become a pandemic in Turkey, as is the case globally. Increase in carotid artery intima-media thickness (CIMT) and erectile dysfunction (ED) may be evident before the clinical signs of cardiovascular disease appear. We aimed to investigate the prevalence of increased CIMT and ED as markers of atherosclerotic disease in patients with MS.
MATERIAL AND METHODS: Thirty-two patients with MS and 29 healthy controls were included. Anthropometric and biochemical parameters, along with total testosterone (TT), high sensitive C-reactive protein (hs-CRP), were recorded. Carotid artery intima-media thickness was measured. Erectile dysfunction was assessed with International Index of Erectile Function.
RESULTS: Patients with MS had higher BMI, fasting plasma glucose, post-prandial plasma glucose, insulin, HOMA-IR, total cholesterol, triglycerides, hs-CRP, and CIMT, whereas TT levels were lower (p<0.0001). The prevalence and severity of erectile dysfunction were higher in patients with MS (p<0.0001). Erectile dysfunction scores correlated inversely with CIMT. MS patients with ED were older and had higher CIMT compared to those without ED. Increase in age and HOMA and decrease in TT increased the risk of ED. When KIMT exceeding the 95th percentile of healthy controls was accepted as a risk factor for CVD, presence of ED was the only determinant for this increase.
CONCLUSIONS: Erectile dysfunction was more prevalent and severe in patients with MS and correlated with subclinical endothelial dysfunction. Total testosterone deficiency was prominent among MS patients. Presence of ED points to an increased risk of cardiovascular disease when MS is present.
Keywords: carotid intima-media thickness, Demography, Erectile Dysfunction - complications, Metabolic Syndrome X - complications
Background
Metabolic syndrome (MS) is characterized by insulin resistance (IR) associated with abdominal obesity, glucose intolerance and diabetes (DM), dyslipidemia, hypertension, and cardiovascular disease (CVD) [1]. Various criteria used the describe the syndrome: World Health Organization (WHO), National Cholesterol Education Programme (NCEP ATP III), and International Diabetes Federation (IDF) [2]. The prevalence is around 25% in the United States and this prevalence increases with age [3]. Metabolic syndrome increases the risk of DM by 5-fold and CVD by 2-fold [4]. Endothelial dysfunction and IR are the early pathogenetic events in MS and they are linked to atherosclerosis and CVD [5].
Erectile dysfunction (ED) is defined as inadequate or non-sustainable penile erection that is required for satisfactory sexual performance [6]. It is not only an alarm sign of CVD, but also has a negative impact on personal relationships, and causes anxiety and loss of self-esteem [7,8]. Neurogenic, hormonal, and psychogenic factors can contribute to ED, but vascular phenomena are thought be most important [9]. Erectile dysfunction is now accepted as an early sign of atherosclerosis and systemic diseases, contrary to the old belief that it is a secondary outcome [10–14]. Even people without evident atherosclerosis show impaired endothelial dysfunction if they have ED [15]. Hence, ED is a preliminary indicator of atherosclerosis and its future complications. Recent research demonstrated an increased prevalence of ED in MS [16–18].
Atherosclerosis is a systemic process that affects the whole arterial system. Carotid arteries can be easily visualized to evaluate the degree of atherosclerosis. Carotid arteria-media thickness (CIMT) has been used to assess the risk of CVD [19].
In this study, we aimed to investigate the prevalence of increased CIMT and ED as markers of atherosclerotic disease in patients with MS.
Material and Methods
STATISTICAL ANALYSIS:
Data were analyzed by SPSS 20.0 (SPSS Inc, Chicago, USA). Continuous variables are expressed as mean ± standard deviation; categorical variables are expressed as percentages. Two groups were compared with Student’s t test. Pearson correlation tests were used to test for the relation between continuous variables. Chi-square test with continuity correction was used to test for the difference between categorical variables. Statistical significance was accepted as a p value less than 0.05. Binary logistic regression was used to assess the determinants of ED.
Results
Baseline demographic and clinical characteristics of the study groups are summarized in Table 1. Systolic and diastolic BP, BMI, Wc, T-Chol, TG, insulin, plasma glucose levels, and hs-CRP were significantly higher in patients with MS. Total testosterone levels were lower in patients with MS when compared to those in the control group (4.8±1.2 ng/ml
Carotid intima-media thickness was higher in the MS group compared to controls (0.76±0.11 mm
Prevalence of ED was higher in patients with MS (65.6%, n=21) when compared to the healthy men in the control group (13.8%, n=4) (p<0.0001). All the cases in the control group were mild; whereas in MS group 6 had mild, 5 had mild-to-moderate, 4 had moderate, and 6 had severe ED. Scores of ED were lower in the MS group compared to controls (15.2±7.5
Mean age was older in MS patients who had ED (41.9±4.8
Increase in age and HOMA and decrease in TT increased the risk of ED (OR 1.594 [CI 95% 1.216–2.086 p=0.001]; OR 1.39 (CI 95% 1.058–1.827 p=0.018); OR 0.193 [CI 0.063–0.596 p=0.004], respectively).
When KIMT exceeding the 95th percentile of healthy controls was accepted as a risk factor for CVD, only presence of ED was a determinant for this increase (OR: 0.032 (95%CI: 0.003–0.353 p=0.005).
Discussion
We demonstrated that prevalence of ED was increased in patients with MS when compared to healthy subjects and this correlated with CIMT.
Carotid intima-media thickness and hs-CRP levels were also higher in patients with MS. We demonstrated that TT levels were lower in patients with MS, and CIMT correlated positively with age and LDL-C, and negatively with TT in the MS group. Increase in age and HOMA and decrease in TT increased the risk of ED and the presence of ED was a determinant for the increase in KIMT.
This study confirms the association between MS, ED, and CVD in a Turkish population. Our patients with MS had adverse metabolic profile compared to the control group. hs-CRP, a reliable marker of inflammation, was higher in the MS group, along with increased CIMT [26]. hs-CRP predicts MS and it is used both as a screening tool and to tailor the statin treatment in patients with CVD [27,28].
Our patients with MS had higher CIMT and CIMT correlated with hs-CRP in the control group, LDL-C in both groups, and TT in the MS group. We could not show any relation between hs-CRP and TT, but recent studies have shown that low TT was correlated with inflammatory markers [29].
Carotid intima-media thickness predicts the cardiovascular disease, but the CIMT-MS relationship is rather controversial. Metabolic syndrome
In our study group, patients with MS had higher frequency of severe ED. Low testosterone, HOMA-IR, and age were predictors of ED in our study group. A study from China confirmed the role of testosterone in ED [32]. Testosterone deficiency has been blamed for worse cardiometabolic profile [33]. Testosterone treatment is beneficial in some components of MS [34]. Increased fat mass (central adiposity), reduced insulin sensitivity, impaired glucose tolerance, and unfavorable lipid profile had been reported [35]. Testosterone improves glucose, lipid, and cholesterol metabolism at the molecular level thorough different mechanism [36].
Different components of MS may have different effects on the development of ED. Hypertension, elevated fasting blood glucose, and low HDL-C have been found to be correlated with ED [37]. Besides MS, ED may accompany other chronic diseases. Although presence of MS was associated with an increased prevalence of ED, we are unable to demonstrate specific effects of different components of MS on ED. Recently, HOMA-IR determination was reported as a useful screening tool for ED [38]. HOMA-IR was a predictor of MS in our study.
Conclusions
ED was more prevalent in patients with MS in this small study group. There was a positive linear relationship between the degree of ED and CIMT. Increased CIMT might be the common reflection of chronic atherosclerotic diseases and ED, and decreased levels of testosterone along with IR may be the missing link between ED and MS. Presence of ED should alert the physician to the high probability of an impending systemic cardiovascular disease and all patients with MS should be questioned regarding ED.
References
1. Lorenzo C, Williams K, Hunt KJ, The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes: Diabetes Care, 2007; 30; 8-13, pmid: 17192325
2. Ivezic-Lalic D, Bergman Markovic B, Kranjcevic K, Diversity of metabolic syndrome criteria in association with cardiovascular diseases – a family medicine-based investigation: Med Sci Monit, 2013; 19; 571-78, pmid: 23852333
3. Ford ES, Giles WH, Dietz WH, Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey: JAMA, 2002; 287; 356-59, pmid: 11790215
4. Grundy SM, Metabolic syndrome pandemic: Arterioscler Thromb Vasc Biol, 2008; 28; 629-36, pmid: 18174459
5. Wheatcroft SB, Williams IL, Shah AM, Pathophysiological implications of insulin resistance on vascular endothelial function: Diabet Med, 2003; 20; 255-68, pmid: 12675638
6. Pohjantahti-Maaroos H, Palomaki A, Hartikainen J, Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis: BMC Cardiovasc Disord, 2011; 11; 36, pmid: 21707993
7. Goldstein I, The mutually reinforcing triad of depressive symptoms, cardiovascular disease, and erectile dysfunction: Am J Cardiol, 2000; 86; 41F-45F, pmid: 10867090
8. Goldstein I, Screening for erectile dysfunction: rationale: Int J Impot Res, 2000; 12(Suppl 4); S147-51, pmid: 11035404
9. Virag R, Bouilly P, Frydman D, Is impotence an arterial disorder? A study of arterial risk factors in 440 impotent men: Lancet, 1985; 1; 181-84, pmid: 2857264
10. Solomon H, Man J, Wierzbicki AS, Erectile dysfunction: cardiovascular risk and the role of the cardiologist: Int J Clin Pract, 2003; 57; 96-99, pmid: 12661790
11. Bocchio M, Desideri G, Scarpelli P, Endothelial cell activation in men with erectile dysfunction without cardiovascular risk factors and overt vascular damage: J Urol, 2004; 171; 1601-4, pmid: 15017230
12. Sullivan ME, Thompson CS, Dashwood MR, Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease?: Cardiovasc Res, 1999; 43; 658-65, pmid: 10690337
13. Bocchio M, Scarpelli P, Necozione S, Intima-media thickening of common carotid arteries is a risk factor for severe erectile dysfunction in men with vascular risk factors but no clinical evidence of atherosclerosis: J Urol, 2005; 173; 526-29, pmid: 15643238
14. Yao F, Huang Y, Zhang Y, Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of coronary heart disease: Int J Androl, 2012; 35; 653-59, pmid: 22519624
15. Averbeck MA, Colares C, de Lira GH, Evaluation of endothelial function with brachial artery ultrasound in men with or without erectile dysfunction and classified as intermediate risk according to the Framingham Score: J Sex Med, 2012; 9; 849-56, pmid: 22239818
16. Corona G, Mannucci E, Petrone L, A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction: J Sex Med, 2007; 4; 789-96, pmid: 17498109
17. Corona G, Mannucci E, Schulman C, Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction: Eur Urol, 2006; 50; 595-604, pmid: 16564129 discussion 604
18. Zambon JP, Mendonca RR, Wroclawski ML, Cardiovascular and metabolic syndrome risk among men with and without erectile dysfunction: case-control study: Sao Paulo Med J, 2010; 128; 137-40, pmid: 20963365
19. Lin E, Hwang W, Imaging assessment of cardiovascular risk in asymptomatic adults: Am J Roentgenol, 2011; 197; W1046-51, pmid: 22109318
20. Ford ES, Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S: Diabetes Care, 2005; 28; 2745-49, pmid: 16249550
21. Sucakli MH, Ozkan F, Inci MF, Effects of smokeless tobacco (Maras powder) use on carotid intima media thickness: Med Sci Monit, 2013; 19; 859-64, pmid: 24129168
22. Saely CH, Rein P, Drexel H, The metabolic syndrome and risk of cardiovascular disease and diabetes: experiences with the new diagnostic criteria from the International Diabetes Federation: Horm Metab Res, 2007; 39; 642-50, pmid: 17846971
23. Rosen RC, Riley A, Wagner G, The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction: Urology, 1997; 49; 822-30, pmid: 9187685
24. Stein JH, Korcarz CE, Hurst RT, Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine: J Am Soc Echocardiogr, 2008; 21; 93-111, pmid: 18261694 quiz 189–90
25. Lim TK, Lim E, Dwivedi G, Normal value of carotid intima-media thickness – a surrogate marker of atherosclerosis: quantitative assessment by B-mode carotid ultrasound: J Am Soc Echocardiogr, 2008; 21; 112-16, pmid: 17764896
26. Yeh E, High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease: Clin Cardiol, 2005; 28; 408-12, pmid: 16250263
27. Oda E, High-sensitivity C-reactive protein and white blood cell count equally predict development of the metabolic syndrome in a Japanese health screening population: Acta Diabetologica, 2013; 50(4); 633-38, pmid: 23619894
28. Koenig W, High-sensitivity C-reactive protein and atherosclerotic disease: From improved risk prediction to risk-guided therapy: Int J Cardiol, 2013; 168(6); 5126-34, pmid: 23978367
29. Bobjer J, Katrinaki M, Tsatsanis C, Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study: PLoS One, 2013; 8; e61466, pmid: 23637840
30. Timóteo A, Carmo M, Ferreira R, Can metabolic syndrome presence predict carotid intima-media thickness?: J Clin Hypretens (Greenwich), 2012; 14; 507-13
31. Yao F, Liu L, Zhang Y, Erectile dysfunction may be the first clinical sign of insulin resistance and endothelial dysfunction in young men: Clin Res Cardiol, 2013; 102; 645-51, pmid: 23681359
32. Liao M, Huang X, Gao Y, Testosterone is associated with erectile dysfunction: a cross-sectional study in Chinese men: PLoS One, 2012; 7; e39234, pmid: 22737230
33. Traish AM, Guay A, Feeley R, The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction: J Androl, 2009; 30; 10-22, pmid: 18641413
34. Jones TH, Arver S, Behre HM, Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study): Diabetes Care, 2011; 34; 828-37, pmid: 21386088
35. Tirabassi G, Gioia A, Giovannini L, Testosterone and cardiovascular risk: Intern Emerg Med, 2013; 8(Suppl 1); S65-69, pmid: 23475207
36. Kelly DM, Jones TH, Testosterone: a metabolic hormone in health and disease: J Endocrinol, 2013; 217(3); R25-45, pmid: 23378050
37. Tan WS, Ng CJ, Khoo EM, The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men’s Health Study): Aging Male, 2011; 14; 231-36, pmid: 22115177
38. Yao F, Liu L, Zhang Y, Erectile dysfunction may be the first clinical sign of insulin resistance and endothelial dysfunction in young men: Clin Res Cardiol, 2013; 102; 645-51, pmid: 23681359
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