Original Article

Lipid Profile and Inflammation in Degenerative Valvular Disease


  • Mehmet Yamak
  • Fuat Sar
  • Özger Akarsu
  • Meltem Gürsu
  • Burcu Hacıoğu
  • Esra Ataoğlu
  • Kazım Korkmaz
  • Savaş Öztürk

Received Date: 04.09.2014 Accepted Date: 19.09.2014 Med Bull Haseki 2015;53(1):62-66


Degenerative valvular heart disease (DVHD) may cause serious cardiac problems and mortality. Determination of the factors related to DVHD may render possible the prevention and/or slowing down the progression of DVHD. In this study, we evaluated the relationship of DVHD with lipid profile, microalbuminuria and high sensitive C-reactive protein (hsCRP) levels.


50 patients (age=65.6±12.4 years) with DVHD were compared with the control group including 20 patients (age=57.3±13.9 years) with left ventricle hypertrophy, but no DVHD. Microalbuminuria, blood lipid parameters and hsCRP levels were measured besides routine biochemical tests. Clinical, laboratory and echocardiographic findings were compared between the groups.


Total cholesterol, HDL-cholesterol and LDL-cholesterol levels were significantly higher in DVHD group (215.26±48.59 mg/dL vs. 177.45±22.47 mg/dL, p=0.001; 45.04±11.03 mg/dL vs. 38.90±11.82 mg/dL, p=0.043 and 138.49±40.69 mg/dL vs. 114.26±16.07 mg/dL, p=0.001) compared with control group. hsCRP and microalbuminuria levels were relatively higher in DVHD group.


Hyperlipidaemia is related to DHVD development, and the progress of DHVD may be related to the inflammatory process. Elevated hsCRP levels may be an indicator of pathologies active in DVHD development. Routine echocardiographic analysis in hypertensive patients with high hsCRP and LDL-cholesterol levels might be useful for screening of DVHD.

Keywords: Atherosclerosis, heart valve disease, inflammation, lipid


Degenerative mitral valve disease involves myxomatous mitral disease, flail mitral valve, mitral valve prolapse (MVP) and Barlow syndrome (1). The pathological changes that cause degenerative aortic valve disease include annular dilatation, leaflet thickening, myxomatous degeneration, and calcification of the annulus and leaflets. These changes lead to a wide spectrum of clinical consequences ranging from mild aortic valve sclerosis to symptomatic aortic stenosis (2). Aortic valve sclerosis is characterized by thickening, increased echogenity and calcification of the valve leaflets. It may lead to symptomatic aortic stenosis that has a poor prognosis unless treated surgically (2). It is seen in 21-26% of individuals older than 65 years; and in 48% of the population aged more than 85 years (2,3). Aortic stenosis (AS) is classified etiologically as senile calcific, bicuspid, rheumatic and congenital. The most frequent reason is chronic inflammation and fibrosis of the valve similar to atherosclerosis of the arteries (4).

Lipoprotein disorder (low high density lipoprotein -HDL- levels, elevated levels of low density lipoprotein -LDL- and lipoprotein-a, and hypertriglyceridemia), smoking, male gender, hypertension, advanced age, diabetes mellitus (DM) may accelerate AS by endothelial dysfunction and fibrosis (5). The duration of hypercholesterolemia has been found to be correlated with the risk of AS in patients with familial hypercholesterolemia (6). Inflammation is an important cause of endothelial dysfunction and aortic sclerosis (7). Aortic sclerosis and endothelial dysfunction share similar risk factors and pathogenesis. Experimental and clinical studies revealed that inflammatory process adds to atherogenesis; and may cause atherosclerotic plaque rupture and erosion (8). C-reactive protein (CRP) is an acute phase protein produced by hepatocytes in response to cytokines like interleukin-6 and tumor necrosis factor-α (9). Inflammatory reaction begins in response to capture of atherogenic lipoproteins by the arterial wall; and causes increased CRP production through cytokine release.

The most extensively studied inflammatory marker acting on atherosclerosis is high sensitive CRP (hsCRP). The production of CRP increases in case of infection, tissue damage and any kind of inflammation (10). Recent studies revealed that hsCRP is a strong predictor of atherosclerosis and vascular deaths; and is superior to lipid levels and other inflammatory markers. This is thought to be due to proatherogenic nature of CRP (11). Besides atherosclerosis; systemic inflammation was shown to be active in patients with AS (12).

Microalbuminuria (MA) is defined as urinary albumin excretion in the range of 20-200 µg/min or 30-300 mg/day (13). Studies have shown that MA is not only a marker of diabetic complications, but also an independent risk factor for cardiovascular diseases (14). MA has been found to be stronger predictor for cardiovascular disease than other classical risk factors including hypercholesterolemia. MA was involved within cardiovascular risk factors in the seventh report of Joint National Committee (JNC-7) (15).

We aimed in this study to examine the relationship of the presence of degenerative valvular heart disease (DVHD) with atherogenesis, inflammation and endothelial dysfunction.


The study was started after obtaining approval from the local ethics committee. Patients with DVHD were chosen as the patient group among patients who had echocardiographic examination in the echocardiography laboratory of our hospital. This group was compared with the control group consisting of patients with left ventricular hypertrophy, but no DVHD. An informed consent form was signed by all patients.

Patients with DM, renal failure, acute ischemic heart disease, advanced heart failure (ejection fraction (EF) less than 40%) and acute infectious disease, obese patients with a body mass index (BMI) more than 30 kg/m2, those using antibiotics, steroid, statin or nonsteroid anti-inflammatory drugs, and patients with smoking history were excluded from the study.

Demographic data of the patients including age and gender were recorded as well as medical histories. Systolic and diastolic blood pressures were measured at optimal conditions. BMI was calculated by the formula of weight/(height)2. Blood samples were obtained for laboratory analysis after 8 hours of fasting for measurement of glucose, total, HDL and LDL cholesterol, triglyceride, HbA1c, creatinine and hsCRP levels, and erythrocyte sedimentation rate. Triglyceride and cholesterol levels were measured by enzymatic calorimetric methods using ABBOT Architect/Aeroset machine. hsCRP levels were measured by nephelometric method using Beckman Coulter IMMAGE Immunochemistry Systems machine. To determine microalbuminuria, 24-hour urine was analysed by turbidometric method using ABBOT Architect/Aeroset machine.

Echocardiographic examinations were performed by the same physician using General Electric Vivid 3 Pro machine.

Statistical analysis was conducted by using SPSS (Statistical Package for Social Sciences) version 14.0 for Windows. Numerical parameters were expressed as mean ± standard deviation (SD). Student t-test and Mann-Whitney U test were used for comparison of the two groups. Yates corrected chi-square test and Fischer’s exact test were used for 2x2 contingency tables of nonnumeric variables when necessary. Correlation analysis of numerical and nonnumeric parameters was performed by Pearson and Spearman’s rho correlation tests, respectively. A p value of less than 0.05 was considered statistically significant.


Fifty patients with DVHD and 20 patients with left ventricular hypertrophy were included in the study as the patient and the control groups. Male/female ratio was 22/28 and 13/7 in the patient and control groups, respectively. The demographic and clinical data of the patients are presented in Table 1. Groups were similar regarding gender, age, weight, height, BMI and blood pressures. The biochemical data of the groups are presented in Table 2. hsCRP and microalbuminuria levels were detected to be significantly higher in the patient group. The patient group had significantly higher levels of total cholesterol, HDL cholesterol and LDL cholesterol (Figure 1).

Aortic valve degeneration was detected in 6 patients (12%), mitral valve degeneration in one patient (2%); while 43 patients (88%) had both disorders. The mean EF in the patient and the control groups were 58.82±3.14% and 59.00±3.08%, respectively (p=0.828).

There was no significant correlation between hsCRP and microalbuminuria levels in the patient group (r=0.004, p=0.972). The results of the logistic regression analysis are presented in Table 3. The occurrence of DVHD was related with hsCRP levels.


The most common reason of acquired AS in developed countries is chronic inflammatory and fibrotic process involving the aortic valve. Elevated total cholesterol, LDL cholesterol, lipoprotein (a), triglyceride, low HDL cholesterol levels, presence of hypertension, DM, male gender, smoking, and advanced age have been found to be related with increased frequency of aortic sclerosis besides being the reasons of endothelial dysfunction and valve damage (3,16,17). The duration of exposure to high cholesterol levels has been reported to be related with AS in patients with familial hypercholesterolemia (6). Pohle et al. found higher progression rates of both coronary and aortic calcification in patients with elevated LDL cholesterol levels (18). In a study by Gerber et al., 23 patients among 246 cases were found to have AS of whom serum total cholesterol, LDL cholesterol and lipoprotein (a) levels were higher than the control subjects (19).

Our findings are consistent with these data. The patient group had significantly higher levels of total cholesterol, HDL cholesterol and LDL cholesterol compared with the control group (Figure 1). There was no difference between the patient and the control groups regarding triglyceride levels. But HDL/total cholesterol ratio was similar in the groups.

Many studies have shown that high CRP level is a good predictor of atherosclerosis (20). hsCRP has been found to be good indicator of endothelial dysfunction (21). Increased inflammatory activity plays important roles in the development of aortic sclerosis. Chandra et al. studied 425 patients, who were admitted to the emergency clinic with chest pain, and found that those with aortic sclerosis had higher CRP levels; and CRP level was correlated with the severity of sclerosis (22). Galante et al. found higher CRP levels in patients, who were operated due to severe degenerative AS without coronary lesions, compared to that in controls. Skowasch et al. reported a strong correlation between serum CRP levels and CRP levels in the valve tissue (23,24). Contrary to these studies, Gunduz et al. found no difference between total cholesterol and CRP levels in patients with mild, moderate and severe AS; similar to our findings (25). There was no correlation of the severity of AS with hypercholesterolemia and CRP levels; while lipid levels were correlated with coronary lesions. Similarly, Jeevanatham et al. reported no relationship between hsCRP levels and the severity of AS; although patients with aortic sclerosis and AS had higher hsCRP levels compared with the control group (26). We found higher hsCRP levels in the patient group compared with the control group in our study.

Degenerative aortic valvular disease is a dynamic process involving hemodynamic and inflammatory factors and also endothelial damage. Microalbuminuria has been shown by many studies to be an important marker of endothelial damage (27). It was also shown to be related with lipid profile and hsCRP levels (28,29). CRP may be a sign of vascular damage and distorted endothelial function which may cause microalbuminuria. Therefore, high plasma hsCRP levels are related with microalbuminuria and endothelial dysfunction.

Stuveling et al. reported that CRP attenuated the relationship between blood pressure and microalbuminuria, however, not the relationship between microalbuminuria and other cardiovascular risk factors (30).

We detected in the present study that microalbuminuria was significantly higher in patients with degenerative aortic valvular disease compared with the control group. But there was no correlation between CRP and microalbuminuria levels. With logistic regression analysis, hsCRP level was detected to be an indicator of DVHD while LDL cholesterol had an effect with borderline statistical significance while microalbuminuria had no effect.

In conclusion; hyperlipidaemia may be related with development of DVHD similar to the inflammatory process in atherosclerosis. Elevated hsCRP levels may be regarded as a general marker of factors acting on this degenerative and inflammatory process. It may be useful to screen hypertensive patients with elevated hsCRP and LDL cholesterol levels with echocardiographic examination for valvular disease.

1.    Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1-7.
2.    Otto CM, Lind BK, Kitzman DW, et al. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med 1999;341:142-7.
3.    Aronow WS, Schwarts KS, Koenigsberg M. Correlation of serum lipids, calcium and phosphorus, diabetes mellitus and history of systemic hypertension with presence or absence of calcified or thickened aortic cusps or root in elderly patients. Am J Cardiol 1987;59:998-9.
4.    Passik CS, Ackermann DM, Pluth JR, et al. Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. Mayo Clin Proc 1987;62:119-23.
5.    Podolec P, Kopec G, Rubic P, et al. [Calcific and degenerative aortic stenosis--pathogenesis and new possibilities of treatment]. Przegl Lek 2004;61:604-8.
6.    Rallidis L, Naoumova RP, Thompson GR, et al. Extent and severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia. Heart 1998;80:583-90.
7.    Mohler ER 3rd, Gannon F, Reynolds C, et al. Bone formation and inflammation in cardiac valves. Circulation 2001;103:1522-8.
8.    Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999;340:115-26.
9.    Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci 1982;389:39-48.
10.    Auer J, Berent R, Lassnig E, et al. C-reactive protein and coronary artery disease. Jpn Heart J 2002;43:607-19.
11.    Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813-8.
12.    Sánchez PL, Santos JL, Kaski JC, et al. Grupo AORTICA (Grupo de Estudio de la Estenosis Aórtica). Relation of circulating C-reactive protein to progression of aortic valve stenosis. Am J Cardiol 2006;97:90-3.
13.    Rodrigo T, Monica A, Donald G. Microalbuminuria: Is a valid predictor of cardiovascular risk? Cleve Clin J Med 2003;70:255-61.
14.    Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, et al. Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol 1999;19:1992-7.
15.    Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-72.
16.    Ghani M, Burwash IG, Chan KL. Cholesterol and triglyceride levels in congenital bicuspid aortic valve: risk factors for aortic stenosis. Circulation 1998;98:699.
17.    Mautner GC, Mautner SL, Cannon RO 3rd, et al. Clinical factors useful in predicting aortic valve structure in patients > 40 years of age with isolated valvular aortic stenosis. Am J Cardiol 1993;72:194-8.
18.    Pohle K, Mäffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001;104:1927-32.
19.    Gerber Y, Goldbourt U, Feinberg MS, et al. Are triglyceride-rich lipoproteins associated with aortic valve sclerosis? A preliminary report. Atherosclerosis 2003;170:301-5.
20.    Tracy RP. Inflammation in cardiovascular disease: cart, horse, or both? Circulation 1998;97:2000-2.
21.    Rifai N, Ridker PM. High-sensitive C-reactive protein: a novel and promising marker of coronary heart disease. Clin Chem 2001;47:403-11.
22.    Chandra HR, Goldstein JA, Choudhary N, et al. Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation. J Am Coll Cardiol 2004;43:169-75.
23.    Galante A, Pietroiusti A, Vellini M, et al. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol 2001;38:1078-82.
24.    Skowasch D, Schrempf S, Preusse CJ, et al. Tissue resident C reactive protein in degenerative aortic valves: correlation with serum C reactive protein concentrations and modification by statins. Heart 2006;92:495-8.
25.    Gunduz H, Akdemir R, Binak E, et al. Can serum lipid and CRP levels predict the “severity” of aortic valve stenosis? Acta Cardiol 2003;58:321-6.
26.    Jeevanantham V, Singh N, Izuora K, et al. Correlation of high sensitivity C-reactive protein and calcific aortic valve disease. Mayo Clin Proc 2007;82:171-4.
27.    Bakris GL. Clinical importance of microalbuminuria in diabetes and hypertension. Curr Hypertens Rep 2004;6:352-6.
28.    Campese VM, Bianchi S, Bigazzi R. Association between hyperlipidaemia and microalbuminuria in essential hypertension. Kidney Int Suppl 1999;71:10-3.
29.    Yan JT, Ye H, Wang DW. The relationship between microalbuminuria and plasma high sensitivite C reactive protein. Zhanghua Xin Xue Guan Bing Za Zhi 2005;33:534-5.
30.    Stuveling EM, Bakker SJ, Hillege HL, et al. PREVEND Study Group. C-reactive protein modifies the relationship between blood pressure and microalbuminuria. Hypertension 2004;43:791-6.