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Keywords:

  • atherosclerosis;
  • carotenoids;
  • elderly men;
  • intima–media thickness

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

Abstract.  Karppi J, Kurl S, Laukkanen JA, Rissanen TH, Kauhanen J (Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio; Lapland Central Hospital, Rovaniemi; Finland). Plasma carotenoids are related to intima – media thickness of the carotid artery wall in men from eastern Finland. J Intern Med 2011; 270: 478–485.

Background.  Several previous epidemiological studies have suggested that high plasma concentrations of carotenoids may slow the development of early atherosclerosis, but results have been inconclusive.

Methods.  We examined the effect of carotenoids on early atherosclerosis in a population-based study. The association between plasma carotenoid concentrations and intima–media thickness of the common carotid artery (CCA-IMT) was investigated in 1212 elderly men (aged 61–80 years) in Eastern Finland. They were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis, and plasma concentrations of carotenoids were measured by high-performance liquid chromatography.

Results.  Men in the lowest quartile of CCA-IMT had significantly higher concentrations of plasma β-cryptoxanthin, lycopene and α-carotene than men in the highest quartile (P for the differences: 0.043, 0.045 and 0.046, respectively), after adjustment for age, examination year, body mass index, smoking, alcohol intake, years of education, symptomatic coronary heart disease (CHD) or CHD history, diabetes, low-density lipoprotein cholesterol, medications and season. The concentrations of plasma β-cryptoxanthin, lycopene and α-carotene decreased linearly with increasing CCA-IMT.

Conclusions.  The results of this study suggest that high plasma concentrations of β-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

Increased intima–media thickness (IMT) of the common carotid artery (CCA) wall (CCA-IMT) represents an early phase of the atherosclerostic process. CCA-IMT is a reliable marker of atherosclerosis that correlates with coronary artery disease (CAD) [1]. Some, but not all, previous studies have shown that high blood concentrations of carotenoids are associated with a decreased risk of carotid atherosclerosis [2–10]. It has been shown that fruits and vegetables rich in carotenoids have beneficial effects, slowing the development of early atherosclerosis [11]. Although the health-related effects of α-carotene, β-carotene and lycopene have been studied quite extensively, little is known about the role of xanthophylls (lutein, zeaxanthin and β-cryptoxanthin) in the prevention of early atherosclerosis.

β-cryptoxanthin is an antioxidant carotenoid, which, unlike lutein and zeaxanthin, has provitamin A activity [12]. Antioxidative activity of xanthophylls has been shown in cell culture and animal models, and reduced oxidative modification of low-density lipoprotein cholesterol (LDL-c) may be one of the mechanisms by which these antioxidants reduce the risk of early atherosclerosis [13–15]. The results of several studies have suggested that serum/plasma concentrations of xanthophylls are inversely related to CCA-IMT. Specifically, the results of a study conducted both in vitro and in vivo suggest that lutein may protect against the progression of atherosclerosis in humans and animals [8]. A modest inverse association between circulating concentrations of β-cryptoxanthin, lutein and zeaxanthin and CCA-IMT is supported by the results of a case–control study [3]. High plasma concentrations of β-cryptoxanthin, lutein and zeaxanthin were also shown to be associated with reduced progression of CCA-IMT in the Los Angeles Atherosclerosis Study [9].

We previously showed that a low serum lycopene concentration was associated with a higher CCA-IMT in middle-aged men [7]. The aim of the present study was to test the hypothesis that CCA-IMT would be greater amongst elderly men with low plasma concentrations of carotenoids (particularly xanthophylls).

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

Study population

The Kuopio Ischaemic Heart Disease Risk Factor study is a population-based, cohort study that was designed to identify a wide range of biological, behavioural, socio-economic and psychosocial risk factors for cardiovascular disease, diabetes and other outcomes in a sample of middle-aged men in Kuopio, Finland, and the surrounding rural communities [16]. The study has been approved by the Research Ethics Committee of the Hospital District of Northern Savo, Kuopio, Finland. All study subjects provided written informed consent. A total of 2682 male participants (82.9% of those eligible), aged 42−60 years, were enrolled in the baseline study between 1984 and 1989. Re-examinations for those examined in the baseline study were conducted between 2005 and 2008. For re-examinations, 1804 men were called of which 1557 were eligible (72 was died, 150 had severe illness and 25 were migrated). Of the 1557 eligible men, 262 were refused, 53 had no contact and one had other reason not to participate. Of the remaining 1241 men aged 61−80 years, high-resolution ultrasound examinations of CCA-IMT and data on plasma carotenoid concentrations were available for 1212.

Ultrasonographic assessment of the intima–media thickness of the common carotid artery

Intima–media thickness of the common carotid artery was assessed by high-resolution B-mode ultrasonography of the right and left CCAs at the distal end, proximal to the carotid bulb. The ultrasound equipment (Esaote Technos MP/Genoa, Italy) included a high-resolution probe. Images were focused on the posterior wall of the right and left CCAs and were recorded on videotape for image analysis. The ultrasonographic examinations were carried out by well-trained ultrasound technicians.

Intima–media thickness measurements were taken through computerized analysis of the videotaped ultrasound images with prowin software (University of Southern California, Los Angeles, CA, USA). This software uses an edge-to-edge detection algorithm, specifically designed for use with ultrasound imaging, that allows automatic detection, tracking and recording of the intima–lumen and media–adventitia interfaces, estimated at ∼100 points, in both the right and left CCAs in a 1.0-cm section [17]. For the present study, four measurements of IMT were used. Mean IMT was computed as the mean of ∼100 IMT measurements in the right CCA and another 100 measurements in the left CCA [18].

To determine the precision of the ultrasonic protocol, a repeat scan was performed for 32 subjects (by another sonographer in 19 subjects and by the same sonographer in the remaining 13). The intrasonographer correlation coefficient was 0.96 for mean CCA-IMT. The intersonographer correlation coefficient for the same carotid segment was 0.97.

Blood sample collection

Subjects were instructed to fast for 12 h and refrain from consuming alcohol for 2 days before blood sampling. Fasting venous blood samples were collected into vacuum tubes (Terumo, Leuven, Belgium) without tourniquet, after the subject had rested in the supine position for 5 min. For the measurement of carotenoid levels, blood was collected in lithium heparin tubes, and plasma was separated immediately after centrifugation in dark tubes and stored at −70 °C until analysis.

Laboratory analyses

Concentrations of plasma α-tocopherol, retinol, lycopene, α-carotene, β-carotene, lutein, zeaxanthin and β-cryptoxanthin were analysed with reversed-phase high-performance liquid chromatography [19]. Plasma samples were mixed with ethanol-butylated hydroxytoluene (BHT) solution containing α-tocopherol acetate, β-apo-8′-carotenal and ultrapure water as internal standards. Hexane–BHT solution was added to the samples, which were then mixed. After extraction, water was added to the samples. The samples were centrifuged and frozen to separate the hexane phase. The hexane layer was evaporated to dryness under a gentle stream of nitrogen at room temperature. After reconstitution, the sample was injected into a pair of Synergy Hydro-RP 80A 4 μm (150 × 4.6 mm) columns (Phenomenex, Torrance, CA, USA) using a Shimadzu system (Kyoto, Japan) and a Beckman 168 diode-array detector (Beckman Coulter, Fullerton, CA, USA). Values below the limit of detection of the method were taken as 0.00 in the statistical analysis.

Concentrations of serum total cholesterol, LDL-c and triglycerides were analysed using enzymatic methods (Thermo Fisher Scientific, Vantaa, Finland). The level of serum high-density lipoprotein cholesterol (HDL-c) was measured from the supernatant after magnesium chloride dextran sulphate precipitation also using an enzymatic method (Thermo Fisher Scientific).

Other measurements

Resting blood pressure was measured in the morning by a trained nurse with a random-zero mercury sphygmomanometer (Hawksley, Lancing, UK). After the subjects had rested for 5 min, three measurements were taken at 2-min intervals whilst the subjects were sitting. The mean of all three measurements was used to calculate the systolic (SBP) and diastolic blood pressure. Body mass index (BMI) was computed as the ratio of weight (kilograms) to the square of height (metres). Education, family history of diabetes, medication and smoking were recorded using a self-administered questionnaire that was checked by the interviewer. Education was coded into three categories based on years of education (<6, 7–11 and ≥12 years). Symptomatic coronary heart disease (CHD) or CHD history was also recorded using a self-administered questionnaire and checked by the interviewer. Family history of CHD was defined as positive if a parent or sibling had a history of the condition. Diabetes mellitus was defined as a fasting blood glucose level ≥6.7 mmol L−1 or a clinical diagnosis of diabetes with dietary, oral antidiabetic or insulin treatment. A subject was defined as a smoker if he/she had ever smoked regularly and had smoked cigarettes, cigars or a pipe within the past month. The number of tobacco packs of cigarettes currently smoked daily and the duration of regular smoking in years were recorded. Examination month was categorized as autumn = 1 (months from August to October, when the intake of berries and vegetables is the highest in Finland) and other months = 0.

Statistical analyses

spss software (version 14.0; SPSS, Inc., Chicago, IL, USA) was used for statistical analyses. Cigarette smoking, symptomatic CHD or CHD history, diabetes, the use of medications such as statins, β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor II antagonists and history of hypertension were reported as percentages. Other subject characteristics were reported as means ± SD. Subjects were grouped into quartiles of CCA-IMT: <0.88 mm, 0.88–0.99 mm, 1.0–1.11 mm and >1.11 mm. The statistical significance of the difference in levels of fat-soluble vitamins and carotenoids between subjects with different demographic characteristics was studied using one-way analysis of variance (anova). The correlations between CCA-IMT and cardiovascular disease risk factors were estimated by Spearman’s correlation coefficients. The associations between plasma concentrations of fat-soluble vitamins, carotenoids and ultrasonographically assessed CCA-IMT were tested for statistical significance using a covariance analysis. Two different sets of covariates were used: model 1 included age and examination year; model 2 included age, examination year, BMI, smoking, alcohol intake, years of education, symptomatic CHD or CHD history, diabetes, LDL-c, use of medications (statins, β-blockers, ACE inhibitors or angiotensin receptor II antagonist), hypertension plus antihypertensive medication and season. Tests were two-tailed, and P-values <0.05 were considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

Demographic characteristics and established cardiovascular disease risk factors are shown in Table 1. All 1212 participants were grouped into CCA-IMT quartiles: <0.88 mm, n = 302; 0.88–0.99 mm, n = 304; 1.10–1.11 mm, n = 303; >1.11 mm, n = 303. Mean age of the participants was 71.6 ± 5.4 years. Compared with participants with CCA-IMT of <0.88 mm, those in the higher quartiles were older, had higher SBP, more frequently had symptomatic CHD or CHD history, were less well educated, consumed less alcohol and had lower concentrations of plasma β-cryptoxanthin, zeaxanthin and lycopene and serum HDL-c. Other characteristics did not differ on the basis of quartile of CCA-IMT.

Table 1. Demographic characteristics of the study population, aged 61−80 years (n = 1212 men)
 Quartile of carotid intima−media thickness (mm)P for heterogeneitya
<0.880.88−0.991.0–1.11>1.11
(= 302)(= 304)(= 303)(= 303)
  1. CHD, coronary heart disease; ACE, angiotensin-converting enzyme inhibitor; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

  2. aanova. Continuous variables are presented as means (SD), and dichotomous variables are presented as percentages.

Demographic characteristics
 Age (years)69.0 (6.0)71.4 (5.5)72.5 (5.1)73.5 (3.9)<0.001
 BMI (kg m−2)27.0 (4.1)27.0 (4.1)27.0 (3.8)27.1 (3.5)0.953
 Current smokers1010970.619
 Cigarette smoking (pack-years)2.4 (10.3)2.3 (10.3)2.2 (9.4)2.8 (10.5)0.911
 Alcohol (g week−1)74.1 (134.6)61.1 (91.8)53.1 (108.0)47.4 (88.2)0.015
 Years of education10.0 (3.7)9.4 (3.6)9.0 (3.2)8.4 (3.3)<0.001
 Symptomatic CHD or CHD history273431390.019
 Diabetes384239380.833
Blood pressure parameters
 Systolic blood pressure (mmHg)133 (16)133 (17)136 (18)136 (18)0.010
 Any β-blocker403938450.410
 ACE inhibitor or angiotensin receptor II antagonist383532360.520
 Hypertension + antihypertensive medication666463690.337
Plasma carotenoids and fat-soluble vitamins (μmol L−1)
 β-cryptoxanthin0.12 (0.12)0.10 (0.09)0.10 (0.10)0.09 (0.08)0.003
 Lutein0.25 (0.08)0.24 (0.10)0.23 (0.08)0.24 (0.10)0.227
 Zeaxanthin0.040 (0.017)0.040 (0.022)0.037 (0.019)0.036 (0.016)0.012
 Lycopene0.11 (0.08)0.09 (0.07)0.08 (0.06)0.08 (0.06)<0.001
 α-carotene0.13 (0.11)0.12 (0.11)0.11 (0.09)0.11 (0.09)0.072
 β-carotene0.47 (0.34)0.45 (0.33)0.45 (0.32)0.43 (0.30)0.498
 α-tocopherol33.7 (8.1)32.4 (7.9)33.0 (7.5)33.0 (7.5)0.246
 Retinol2.20 (0.53)2.17 (0.53)2.12 (0.52)2.15 (0.54)0.299
Serum lipids and lipoproteins (mmol L−1)
 Total cholesterol4.84 (0.96)4.67 (0.94)4.76 (1.01)4.69 (0.93)0.115
 LDL cholesterol2.91 (0.83)2.82 (0.78)2.93 (0.87)2.86 (0.79)0.368
 HDL cholesterol1.19 (0.32)1.12 (0.27)1.10 (0.30)1.11 (0.28)<0.001
 Triglycerides1.22 (0.65)1.20 (0.60)1.17 (0.51)1.21 (0.54)0.791
 Statin medication363635350.988

There was a high correlation between several carotenoids: α-carotene with β-carotene (r = 0.77), lutein with zeaxanthin (r = 0.65) and lycopene with lutein, zeaxanthin, β-cryptoxanthin, α-carotene and β-carotene (r = 0.18−0.31). Plasma β-cryptoxanthin concentration was negatively correlated with mean CCA-IMT (Spearman’s correlation coefficient: = −0.090, = 0.002). The strongest correlations were observed between mean CCA-IMT and age (= 0.292, < 0.001) and years of education (= −0.198, < 0.001). Furthermore, significant inverse correlations were observed between mean CCA-IMT and alcohol consumption, serum HDL-c and plasma lycopene, lutein, zeaxanthin and α-carotene (Table 2). There were positive correlations between mean CCA-IMT and age, SBP and symptomatic CHD or CHD history. Age and smoking were inversely associated with the concentration of most of the carotenoids (data not shown). Plasma concentrations of lycopene (< 0.001) and zeaxanthin (= 0.003) were lower in older men (>75 years). Smokers had significantly lower concentrations of carotenoids than nonsmokers (β-cryptoxanthin: 0.070 vs. 0.11 μmol L−1; lutein: 0.20 vs. 0.25 μmol L−1; zeaxanthin: 0.039 vs. 0.032 μmol L−1; α-carotene: 0.090 vs. 0.12 μmol L−1; and β-carotene: 0.33 vs. 0.46 μmol L−1).

Table 2. Spearman’s correlation coefficients and statistical significance for the association between mean intima–media thickness of the common carotid artery and cardiovascular disease risk factors in elderly men in eastern Finland (n = 1212)
 rP
  1. BMI, body mass index; CHD, coronary heart disease; ACE, angiotensin-converting enzyme inhibitor; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

Age (years)0.292<0.001
Systolic blood pressure (mmHg)0.0880.002
BMI (kg m−2)0.0240.411
Cigarettes packs day−1 × years of smoking0.0250.377
Years of education−0.198<0.001
Alcohol (g week−1)−0.0980.001
Symptomatic CHD or CHD history0.0690.016
Diabetes0.0190.509
Statin−0.0140.637
β-blocker0.0290.318
ACE inhibitor or angiotensin receptor II antagonist−0.0240.407
Hypertension + antihypertensive medication0.0190.514
Serum cholesterol (mmol L−1)−0.0520.069
Serum LDL cholesterol (mmol L−1)−0.0210.473
Serum HDL cholesterol (mmol L−1)−0.104<0.001
Serum triglycerides (mmol L−1)0.0270.342
Plasma β-cryptoxanthin (μmol L−1)−0.0900.002
Plasma lycopene (μmol L−1)−0.138<0.001
Plasma lutein (μmol L−1)−0.0600.037
Plasma zeaxanthin (μmol L−1)−0.107<0.001
Plasma α-carotene (μmol L−1)−0.0770.008
Plasma β-carotene (μmol L−1)−0.0500.085
Plasma α-tocopherol (μmol L−1)−0.0120.679
Plasma retinol (μmol L−1)−0.0470.104

In a covariance analysis, after adjustment for age and examination year, we observed that men in the highest quartile of CCA-IMT (>1.11 mm) had significantly lower concentrations of plasma β-cryptoxanthin, lycopene, α-carotene and β-carotene, and the concentrations were linearly dependent on of CCA-IMT. After additional adjustment for other covariates, men in the highest quartile of CCA-IMT had significantly lower concentrations of plasma β-cryptoxanthin, lycopene and α-carotene (P-values for the differences were 0.043, 0.045 and 0.046, respectively) than men in the lower three quartiles. The decline in the concentrations of β-cryptoxanthin, lycopene and α-carotene was linearly dependent on CCA-IMT. The P-values for the linear trend for β-cryptoxanthin, lycopene and α-carotene in model 1 were 0.006, 0.008 and 0.003, respectively; in model 2, the corresponding P-values were 0.014, 0.038 and 0.007. Plasma concentrations of lutein, zeaxanthin and β-carotene were not related to CCA-IMT (Table 3).

Table 3. Adjusted plasma carotenoid and fat-soluble vitamin concentrations by quartile of common carotid artery intima–media thickness (n = 1212 men)
 Quartile of CCA-IMT (mm)P for linear trenda
<0.880.88–0.991.0–1.11>1.11
(= 302)(= 304)(= 303)(= 303)
  1. BMI, body mass index; CHD, coronary heart disease; ACE, angiotensin-converting enzyme inhibitor; LDL-c, low-density lipoprotein cholesterol; CCA-IMT, intima–media thickness of the common carotid artery wall.

  2. aAdjusted P-value from covariance analysis. bAdjusted for age, examination year, BMI, current smokers, alcohol intake, years of education, symptomatic CHD or CHD history, diabetes, LDL-c, medications (statins, β-blockers, ACE inhibitors or angiotensin receptor II antagonists), hypertension + antihypertensive medication and season.

Model 1: adjusted for age and examination year (μmol L−1)
 β-cryptoxanthin0.12 (0.11–0.13)0.10 (0.09–1.11)0.10 (0.09–0.11)0.096 (0.09–0.11)0.006
 Lutein0.25 (0.23–0.26)0.24 (0.23–0.25)0.24 (0.23–0.25)0.24 (0.23–0.25)0.141
 Zeaxanthin0.039 (0.037–0.041)0.039 (0.037–0.042)0.037 (0.035–0.039)0.037 (0.035–0.039)0.141
 Lycopene0.10 (0.093–0.109)0.09 (0.08–0.102)0.083 (0.076–0.091)0.086 (0.078–0.094)0.008
 α-carotene0.13 (0.12–0.115)0.12 (0.11–0.13)0.11 (0.10–0.12)0.11 (0.10–0.12)0.003
 β-carotene0.48 (0.44–0.52)0.45 (0.42–0.49)0.44 (0.41–0.48)0.43 (0.39–0.46)0.041
 Retinol2.20 (2.13–2.26)2.17 (2.11–2.23)2.12 (2.06–2.18)2.15 (2.09–2.21)0.161
 α-tocopherol33.3 (32.4–34.2)32.4 (31.5–33.2)33.2 (32.3–34.0)33.3 (32.4–34.2)0.708
Model 2: multivariate adjustedb (μmol L−1)
 β-cryptoxanthin0.12 (0.11–0.13)0.10 (0.09–1.11)0.10 (0.09–0.11)0.098 (0.087–0.11)0.014
 Lutein0.25 (0.24–0.26)0.25 (0.24–0.26)0.23 (0.22–0.24)0.24 (0.23–0.25)0.180
 Zeaxanthin0.039 (0.037–0.041)0.040 (0.038–0.042)0.037 (0.035–0.039)0.037 (0.035–0.039)0.078
 Lycopene0.099 (0.091–0.107)0.090 (0.082–0.097)0.083 (0.075–0.091)0.089 (0.081–0.096)0.038
 α-carotene0.13 (0.12–0.14)0.12 (0.11–0.13)0.11 (0.10–0.12)0.11 (0.099–0.12)0.007
 β-carotene0.48 (0.44–0.51)0.45 (0.42–0.49)0.44 (0.40–0.47)0.43 (0.40–0.47)0.083
 Retinol2.20 (2.14–2.26)2.18 (2.12–2.24)2.12 (2.06–2.18)2.14 (2.08–2.20)0.090
 α-tocopherol33.3 (32.6–34.1)32.6 (31.9–33.4)32.9 (32.1–33.6)33.3 (32.5–34.0)0.925

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

The primary finding of our population-based prospective study is that low plasma concentrations of β-cryptoxanthin, lycopene and α-carotene are associated with carotid atherosclerosis. In our study, elevated CCA-IMT was significantly associated with low concentrations of β-cryptoxanthin, lycopene and α-carotene amongst elderly men.

Previous epidemiological studies have suggested that high blood concentrations of carotenoids are associated with decreased risk of carotid atherosclerosis, although the results have been inconclusive. There has been an increase in the number of reports of the importance of oxygenated carotenoids in the prevention of the risk of early atherosclerosis [3]. It was shown in a cross-sectional study that cases with increased CCA-IMT had statistically lower concentrations of lutein, zeaxanthin and β-cryptoxanthin, compared with controls, whereas levels of carotenoids were not related to the extent of atherosclerosis [3]. Epidemiological studies of atherosclerotic progression [8, 9] have shown that the increase in CCA-IMT was significantly associated with plasma levels of lutein, zeaxanthin, β-cryptoxanthin and α-carotene, but not with β-carotene. In a previous study, atherosclerosis risk decreased with increasing plasma α-carotene and β-carotene concentrations [2]. Elderly men with higher plasma concentrations of β-carotene were shown to have thinner artery walls and small or no plaques in their carotid arteries [4]. Patients with carotid artery disease had lower plasma concentrations of lutein, zeaxanthin and β-cryptoxanthin compared with healthy controls [20]. Our results with β-cryptoxanthin, lycopene and α-carotene are in agreement with the findings of previous studies. By contrast, plasma concentrations of lutein, zeaxanthin and β-carotene were not related to CCA-IMT in our study.

Oxidative modification of LDL-c is thought to play an important role in the initiation of atherosclerosis. Several studies have shown that foods rich in carotenoids may reduce the risk of atherosclerosis by protecting LDL-c from oxidative modification [21]. Antioxidant activities of the carotenoids are based on the electron-rich conjugated system of the polyene chain and are responsible for quenching singlet oxygen and scavenging free radicals to terminate adverse chain reactions [22]. The results of a previous study have shown that lycopene scavenges radical cations more extensively than β-carotene, i.e. reduces more radicals during an equivalent period [23]. Lycopene is also the most efficient quencher of singlet oxygen [24].

Smoking is a well-known risk factor of atherosclerosis. In the present study, smokers and older men had lower concentrations of plasma carotenoids (i.e. β-cryptoxanthin and α-carotene) than nonsmokers and younger men. This may partly be explained by differences in dietary habits, as well as smoking or ageing. We adjusted for age and smoking to eliminate the effect of these factors. Smokers had lower β-cryptoxanthin concentrations and lower cholesterol-adjusted β-cryptoxanthin concentrations as well as increased LDL oxidizability compared with nonsmokers [25].

Our study population consisted of elderly men, and most of them used medications (e.g. statins, antihypertensive drugs, therapeutic agents for angina pectoris and heart disease); therefore, we included medications in covariance analysis as confounding factors. Possibly because of the use of statins, the concentration of LDL-c did not differ between CCA-IMT groups. By contrast, HDL-c concentrations were highest in subjects with the thinnest CCA-IMT.

The mean CCA-IMT in our subjects was somewhat higher than that reported in most other studies [9, 26–28]. This is consistent with the high incidence of clinical CAD in eastern Finland. In our study, the mean plasma β-cryptoxanthin, lycopene and α-carotene concentrations were much lower than values reported in most other population-based studies from European countries; these studies have demonstrated two to fourfold higher concentrations than in the present study [29]. The most likely explanation for this is the low dietary intake of β-cryptoxanthin, lycopene and α-carotene in Finland [30–33] in comparison with other European countries [34, 35]. Low concentrations of β-cryptoxanthin, lycopene and α-carotene may explain the strength of the relationship between the level of these carotenoids and CCA-IMT. One explanation for the weak effect of carotenoids on CCA-IMT found in some studies may be the lack of low circulating concentrations of carotenoids, despite high tissue concentrations.

It is generally considered that a combination of different antioxidants, as found in fruits and vegetables, rather than a single compound, is most likely to have the greatest health benefits. The combination of phenolic compounds and carotenoids was shown to have synergistic effects by preventing human LDL-c oxidation more effectively than carotenoids alone [36]. A synergistic effect of antioxidants may have affected the results in the present study. It is possible that the plasma concentrations of β-cryptoxanthin, lycopene and α-carotene are representative of other beneficial dietary factors. However, the diet of elderly subjects is often incomplete, and this may to some extent have influenced the results.

The strengths of this study include its population-based design, wide variety of biochemical, behavioural, health and socio-economic covariates and the correlations with CCA-IMT measurements. The limitations include the lack of nutrient intake data and the cross-sectional nature of our study. As the different measurements were not assessed concurrently, a temporal relationship cannot be inferred [10]. Further studies are needed to investigate the temporal relationship between carotenoid levels and CCA-IMT. Other factors, such as inflammation markers, might also be associated with atherosclerosis and affect the blood concentration of carotenoids [9].

In conclusion, the results of the present study show that high plasma concentrations of β-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland. Further follow-up studies are needed to examine the progression of early atherosclerosis.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

This study was supported by the Yrjö Janhnsson Foundation, the Aleksanteri Mikkonen Foundation and the Aarne and Aili Turunen Foundation (J. Karppi). The authors thank the staff of the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland for helping with data collection.

Conflict of interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References

None of the authors has any conflicts of interest to declare.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Conflict of interest
  9. References
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