Metabolic Syndrome and Subclinical Carotid Atherosclerosis Among Chinese Elderly People Living in a Rural Community

Abstract

Background:

The relationship between the metabolic syndrome and subclinical atherosclerosis among elderly people remains controversial. We seek to investigate the associations of metabolic syndrome and its components with subclinical carotid atherosclerosis in older people living in rural China.

Methods:

This cross-sectional study included 911 participants (age ≥60 years, 59.4% women) of the community-based Confucius Hometown Aging Project in Shandong, China, who were free of clinical cardiovascular disease. In 2010–2011, data were collected through interviews, clinical examinations, and laboratory tests. Carotid intima media thickness (cIMT) and carotid artery plaque were assessed using ultrasonography. Metabolic syndrome was defined by four sets of criteria. Data were analyzed with multiple general linear and logistic regression models.

Results:

Carotid plaque was detected in 514 (56.4%) persons. Depending on the defining criteria, prevalence of metabolic syndrome ranged from 30.6% to 56.9%. Hypertension, elevated blood pressure (≥130/85 mmHg), diabetes/prediabetes, and high fasting plasma glucose (≥5.6 mmol/L) were significantly associated with an increased likelihood of carotid plaque, whereas an increased cIMT was associated with elevated blood pressure and hypertension (P<0.05). Obesity, high triglycerides, and dyslipidemia were not associated with carotid artery plaque or cIMT. The significant association of metabolic syndrome with an increased likelihood of carotid plaque disappeared when elevated blood pressure and high plasma glucose were added to the models. Metabolic syndrome was not associated with cIMT.

Conclusions:

Metabolic syndrome is associated with subclinical carotid plaque among Chinese elderly people, driven primarily by elevated blood pressure and hyperglycemia. Older adults with metabolic syndrome, especially those with high blood pressure and hyperglycemia, may benefit from evaluation for subclinical atherosclerosis.

Introduction

Metabolic syndrome is a constellation of multiple interrelated cardiometabolic risk factors, such as high blood pressure, hyperglycemia, central adiposity, and dyslipidemia. Epidemiological studies have shown that metabolic syndrome is increasingly common in Asian populations, including Chinese people.^1,2 It has been well established that metabolic syndrome confers an increased risk for cardiovascular diseases (CVDs) in young and middle-aged people,^3,4 although a weaker association among older people has been suggested.⁵ Measures of subclinical atherosclerosis, such as increased carotid intima media thickness (cIMT) and carotid artery plaque, are predictive of cardiovascular events,^6,7 suggesting subclinical atherosclerosis may represent an early phase of the continuum of the atherosclerotic process leading to clinical CVDs. Thus, establishing the association between metabolic syndrome and markers of subclinical atherosclerosis among elderly people may help to improve risk stratification for cardiovascular events and thus to identify subgroups at an increased risk of clinical CVDs for early preventive and therapeutic intervention.

Population-based studies have rather consistently revealed an association between metabolic syndrome and measures of subclinical atherosclerosis (e.g., carotid plaque and increased cIMT) among young and middle-aged people.^8

–11 By contrast, extant studies that explore the relationship between metabolic syndrome and atherosclerotic disorders among older adults have yielded mixed results; some studies have suggested a positive association of metabolic syndrome with clinical CVDs and subclinical atherosclerosis,^12
–14 whereas others have found no or only a weak association.^5,15,16 Previously, we have reported that metabolic syndrome, as a highly prevalent condition among Chinese older people living in a rural area, is associated with major CVDs (e.g., heart disease and stroke), especially with regard to cardiovascular multimorbidity.¹⁷ It is plausible to hypothesize that metabolic syndrome is associated with subclinical atherosclerosis among elderly people without clinical CVDs. In the current study, we seek to explore this hypothesis by investigating the association of metabolic syndrome with markers of carotid atherosclerosis and the role of metabolic syndrome components in their association among Chinese elderly people who were free of clinical CVDs.

Methods

Study participants

This is a population-based cross-sectional study. The study participants were from the Confucius Hometown Aging Project (CHAP), as previously reported.^17,18 The CHAP was conducted by the Jining First People's Hospital and Jining Medical University in Shandong Province, China, in collaboration with the Aging Research Center at Karolinska Institutet in Stockholm, Sweden. The overall aim of the CHAP was to investigate the role of vascular risk factors and atherosclerotic mechanisms in aging and health. Eligible participants for CHAP included all residents who were aged ≥60 years and were living in the Xing Long Zhuang community in June, 2010, a rural area located approximately 20 km from Qufu (Hometown of Confucius) in Shandong, China. From June, 2010, to July, 2011, data were collected through interviews, clinical examinations, and laboratory tests. All assessments were carried out by nurses, physicians, and laboratory technicians from the Xing Long Zhuang Coal Mine Hospital, which provides routine medical and health care services to residents of the local community. Before the assessments, research staff for the CHAP was trained by senior researchers and specialists from the Aging Research Center at Karolinska Institutet.

Of all eligible subjects (n=1743), 205 either refused to participate or had missing demographic information, and 1538 subjects (88.2%) were examined at baseline. Because we intended to examine the association of metabolic syndrome with subclinical carotid atherosclerosis, we further excluded 627 people who were identified at the baseline to have clinical stroke, coronary heart disease, or heart failure, leaving 911 persons for the current analysis.

The CHAP protocols were reviewed and approved by the Ethics Committee at the Jining First People's Hospital of Jining Medical University in Shandong, China. Written informed consent was obtained from participants, or from informants, in the case of cognitively impaired persons. Research within the CHAP had been conducted according to the ethical principles expressed in the Declaration of Helsinki.

Data collection

Data collection was conducted following a questionnaire that was developed from the World Health Organization STEPwise approach to Surveillance and the Study on Global Ageing and Adult Health.^19,20 We collected data on demographics, lifestyle factors (e.g., smoking, alcohol consumption, and leisure activities), cardiometabolic risk factors (e.g., blood pressure, obesity, and serum lipids), medical history (e.g., diabetes, hypertension, heart disease, and stroke), and use of medications (e.g., antihypertensive, hypolipidemic, and hypoglycemic agents) in the 2 weeks prior to the survey.

We measured weight and height with participants wearing light clothes and no shoes. Body mass index (BMI) was calculated as weight (in kilograms) divided by height (in meters) squared. Waist circumference was measured at a point midway between the lowest rib and the iliac crest in a horizontal plane using nonelastic tape. After at least a 5-min rest, arterial blood pressure (Korotkoff phase I for systolic and phase V for diastolic pressure) was measured in a sitting position on the right arm using a mercury sphygmomanometer with the cuff maintained at the heart level. We used a color Doppler ultrasonographic system (Vivid 7 ultrasound system and a 7- to 10-MHz transducer) to assess internal cIMT and carotid artery plaque following a standard protocol.²¹ Briefly, the subject was in the supine position and the head turned 45° from the side being scanned, a region 1–1.5 cm to the carotid bifurcation was identified and scanned in the internal carotid artery. When an optimal longitudinal image was obtained, it was frozen. The cIMT was measured as the distance between the lumen–intima interface and the media–adventitia interface in the areas devoid of plaque for both sides of internal carotid arteries. The cIMT was recorded to the nearest 0.1 mm. The average of three measurements at one visit was recorded, and the mean of left and right cIMT was used in the analysis. Presence of carotid plaque was defined as focal encroachment of internal carotid artery walls in either side. All participants were examined by one clinical sonographer alone blinded to participants' clinical and laboratory information.

After overnight fasting, peripheral blood sample was taken at the research hospital. Fasting plasma glucose (FPG), triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C) were measured using the enzymology methods on an automatic Biochemical Analyzer (Olympus AU400, Olympus Optical Co., Ltd., Tokyo, Japan) at the hospital laboratory that was certified and licensed by the local technical authority.

Definitions of metabolic syndrome

Metabolic syndrome was defined according to four sets of criteria, i.e., the Third Report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III),²² the International Diabetes Federation (IDF),²³ the IDF/American Heart Association (AHA),²⁴ and the Chinese Diabetes Society (CDS) of Chinese Medical Association,²⁵ as briefly summarized in Table 1.

Table 1.

Four Sets of Defining Criteria for the Metabolic Syndrome

Traits of metabolic syndrome	NCEP ATP III criteria (at least three traits)	IDF criteria (abdominal obesity plus any two of the other traits)	IDF/AHA criteria (at least three traits)	CDS criteria (at least three traits) ^a
Body mass index	—	—	—	≥25 kg/m²
Waist circumference	Men ≥102 cm; Women ≥88 cm	Chinese men ≥90 cm; Chinese women ≥80 cm	Chinese men ≥85 cm; Chinese women ≥80 cm	—
Blood pressure	≥130/85 mmHg or use of antihypertensive drugs	≥130/85 mmHg or use of antihypertensive drugs	≥130/85 mmHg or use of antihypertensive drugs	≥140/90 mmHg or use of antihypertensive drugs
Fasting plasma glucose	≥6.1 mmol/L or use of hypoglycemic drugs	≥5.6 mmol/L or use of hypoglycemic drugs	≥5.6 mmol/L or use of hypoglycemic drugs	≥6.1 mmol/L or use of hypoglycemic drugs
Triglycerides	(1.7 mmol/L or use of hypolipidemic drugs	(1.7 mmol/L or use of hypolipidemic drugs	(1.7 mmol/L or use of hypolipidemic drugs	(1.7 mmol/L or use of hypolipidemic drugs
High density lipoprotein cholesterol	Men <1.04 mmol/L, women <1.29 mmol/L, or use of hypolipidemic drugs	Men <1.04 mmol/L, women <1.29 mmol/L, or use of hypolipidemic drugs	Men <1.04 mmol/L, women <1.29 mmol/L, or use of hypolipidemic drugs	Men <0.9 mmol/L, women <1.0 mmol/L, or use of hypolipidemic drugs

High triglycerides and low high-density lipoprotein cholesterol were combined to consider as one trait (dyslipidemia) in the CDS criteria.

NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III; IDF, International Diabetes Federation; AHA, American Heart Association; CDS, Chinese Diabetes Society.

Statistical analysis

The statistical differences in characteristics of the study participants by sex were tested using the t-test for continuous variables with normal distribution, and the chi-squared test for categorical variables. Log transformation was performed for TGs before performing a t-test due to skewed distribution. We employed general linear regression model to estimate the β-coefficient and 95% confidence interval (CI) of cIMT associated with metabolic syndrome and its individual traits, and a logistic regression model to estimate the odds ratio (OR) and 95% CI of carotid plaque related to metabolic syndrome and its traits.

We reported the results mainly from two models: Model 1 was controlled for age, sex, and education, and model 2 was additionally controlled for smoking, alcohol consumption, and physical inactivity. When examining the association between metabolic syndrome and measures of carotid atherosclerosis (carotid plaque and cIMT), we also reported the results from model 3 in which the potential role of elevated blood pressure and high FPG in the association of metabolic syndrome with markers of carotid atherosclerosis was evaluated. The statistical interaction was tested by simultaneously including the independent variables and their cross-product term in the same model. Statistical significance was set at P≤0.05. IBM SPSS Statistics 20 for Windows (IBM SPSS Inc., Chicago, IL) was used for all analyses.

Results

Table 2 shows characteristics of study participants by sex. The mean age of all participants was 68.1 [standard deviation (SD) 4.9] years. Men were more likely than women to receive more years of education, smoke, drink alcohol, participate in physical activity, and have higher mean cIMT (P<0.001), whereas women had a higher mean level of BMI, systolic pressure, TGs, and HDL-C, and a higher prevalence of metabolic syndrome defined by all four sets of criteria than men (P<0.05). Of the 911 participants, carotid artery plaque was detected in 514 persons (56.4%), and men had a higher prevalence of carotid plaque than women (64.1% vs. 51.2%, P<0.001). There was no significant sex difference in mean age, waist circumference, diastolic pressure, and FPG, and in the distributions of use of antihypertensive drugs, antidiabetic agents, and hypolipidemic drugs (P>0.05) (Table 2)

Table 2.

Characteristics of Study Participants by Sex

Characteristics	Total (n=911)	Men (n=370)	Women (n=541)	P value ^a
Age (years), mean (SD)	68.1 (4.9)	68.2 (5.2)	68.0 (4.8)	0.515
Education (years), mean (SD)	4.0 (3.4)	5.6 (3.4)	2.8 (3.0)	<0.001
Ever smoking, n (%)	258 (28.4)	215 (58.1)	43 (8.0)	<0.001
Alcohol consumption, n (%)	180 (19.9)	158 (42.8)	22 (4.1)	<0.001
Physical inactivity, n (%)	753 (82.7)	267 (72.2)	486 (89.8)	<0.001
Body mass index (kg/m²), mean (SD)	26.1 (3.9)	25.8 (3.9)	26.3 (4.0)	0.045
Waist circumference (cm), mean (SD)	92.2 (8.6)	91.9 (9.2)	92.3 (8.2)	0.550
Systolic pressure (mmHg), mean (SD)	147.6 (23.4)	143.9 (22.4)	150.1 (23.7)	<0.001
Diastolic pressure (mmHg), mean (SD)	87.0 (12.4)	87.9 (11.9)	86.4 (12.7)	0.077
Triglycerides (mmol/L), median (IQR)	1.3 (0.9–1.8)	1.1 (0.8–1.6)	1.4 (1.0–1.9)	<0.001
HDL-C (mmol/L), mean (SD)	1.40 (0.32)	1.36 (0.35)	1.43 (0.30)	0.002
FPG (mmol/L), mean (SD)	5.6 (1.5)	5.5 (1.4)	5.7 (1.6)	0.100
Use of antihypertensive agents, n (%)	347 (38.1)	145 (39.2)	202 (37.4)	0.587
Use of antidiabetic agents, n (%)	128 (14.1)	49 (13.3)	79 (14.6)	0.576
Use of hypolipidemic drugs, n (%)	106 (11.7)	41 (11.1)	65 (12.1)	0.630
Metabolic syndrome, n (%)
NCEP ATP III criteria (2001)	381 (42.4)	89 (24.3)	292 (54.9)	<0.001
IDF criteria (2005)	486 (54.0)	155 (42.2)	331 (62.1)	<0.001
IDF/AHA criteria (2009)	513 (56.9)	179 (48.6)	334 (62.7)	<0.001
CDS criteria (2004)	274 (30.6)	94 (26.0)	180 (33.7)	0.014
cIMT (mm), mean (SD)	1.2 (0.4)	1.2 (0.4)	1.1 (0.3)	<0.001
Presence of carotid plaque, n (%)	514 (56.4)	237 (64.1)	277 (51.2)	<0.001

P value is for test of difference between men and women.

SD, standard deviation; IQR, interquartile range; HDL-C, high-density lipoprotein cholesterol; FPG, fasting plasma glucose; NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III; IDF, International Diabetes Federation; AHA, American Heart Association; CDS, Chinese Diabetes Society; cIMT, carotid intima media thickness.

After controlling for age, sex, and education, cIMT was significantly associated with elevated blood pressure (≥130/85 mmHg) and hypertension (≥140/90 mmHg), while presence of carotid plaque was associated with elevated blood pressure, hypertension, high FPG (≥5.6 mmol/L), and diabetes/prediabetes (Table 3, model 1). Further controlling for smoking, alcohol consumption, and physical inactivity did not substantially affect the results (Table 3, model 2). There was no significant association of abdominal obesity, overweight/obesity, high TGs, low HDL-C, and dyslipidemia with either cIMT or carotid artery plaque.

Table 3.

Association of Carotid Plaque and Carotid Intima Media Thickness with Individual Components of Metabolic Syndrome

		Presence of carotid artery plaque			Carotid intima-media thickness (mm)
			Odds ratio (95% confidence interval)		β (95% confidence interval)
Traits of metabolic syndrome	No. of subjects	No. of cases	Model 1 ^c	Model 2 ^c	Model 1 ^c	Model 2 ^c
Abdominal obesity^a
No	76	47	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	826	461	0.92 (0.55–1.52)	0.88 (0.53–1.48)	−0.08 (–0.17–0.01)	−0.08 (–0.17–0.01)
Overweight/obesity^b
No	372	210	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	525	292	1.05 (0.80–1.39)	1.02 (0.77–1.35)	0.02 (–0.03–0.07)	0.02 (–0.03–0.06)
Elevated blood pressure^a
No	148	67	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	762	446	1.73 (1.20–2.50)	1.71 (1.18–2.47)	0.11 (0.05–0.17)	0.11 (0.05–0.18)
Hypertension^b
No	259	119	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	651	394	1.79 (1.33–2.42)	1.77 (1.31–2.40)	0.12 (0.06–0.17)	0.12 (0.07–0.17)
High FPG^a
No	594	313	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	313	200	1.62 (1.21–2.17)	1.67 (1.24–2.23)	0.04 (–0.01–0.09)	0.05 (0.00–0.10)
Diabetes/prediabetes^b
No	690	372	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	217	141	1.68 (1.22–2.33)	1.73 (1.24–2.40)	0.02 (–0.04–0.08)	0.03 (–0.03–0.08)
High triglycerides^a
No	584	327	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	325	186	1.15 (0.87–1.52)	1.11 (0.83–1.47)	0.00 (–0.05–0.05)	−0.01 (–0.05–0.05)
Low HDL-C^a
No	581	333	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	328	180	1.01 (0.76–1.34)	0.97 (0.73–1.29)	−0.02 (–0.07–0.03)	−0.02 (–0.07–0.03)
Dyslipidemia^b
No	572	319	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	337	194	1.18 (0.89–1.57)	1.14 (0.86–1.52)	0.00 (–0.05–0.05)	0.00 (–0.05–0.05)

Metabolic syndrome components were defined according to the International Diabetes Federation/American Heart Association criteria.

Metabolic syndrome components were defined according to the Chinese Diabetes Society criteria.

Model 1 was controlled for age, sex, and education, and model 2 was further controlled for ever smoking, alcohol consumption, and physical inactivity.

FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol.

The overall prevalence of metabolic syndrome was 30.6% (95% CI 27.6%–33.6%) defined by the CDS criteria, 42.4% (39.1%–45.6%) by the NCEP ATP III criteria, 54.0% (50.7%–57.3%) by the IDF criteria, and 56.9% (53.7%–60.2%) by the IDF/AHA criteria. After controlling for age, sex, and education, metabolic syndrome was significantly associated with an over 40% increased OR of having carotid plaque (Table 4, model 1). Further controlling for smoking, alcohol consumption, and physical inactivity only slightly attenuated the association between metabolic syndrome and carotid plaque (Table 4, model 2). Finally, when elevated blood pressure and high FPG were added to model 2, the association between metabolic syndrome and carotid plaque largely disappeared (Table 4, model 3). The ORs of having carotid artery plaque associated with metabolic syndrome were generally comparable across the four sets of defining criteria for metabolic syndrome. There was no significant association between metabolic syndrome and cIMT (Table 4, models 1–3). There was no statistical interaction between metabolic syndrome and sex on either cIMT or presence of carotid plaque (data not shown).

Table 4.

Association of Carotid Plaque and Carotid Intima Media Thickness with Metabolic Syndrome

		Presence of carotid artery plaque				Carotid intima-media thickness (mm)
			Odds ratio (95% confidence interval)			β-coefficient (95% confidence interval)
Metabolic syndrome by four definitions	No. of subjects	No. of cases	Model 1 ^a	Model 2 ^a	Model 3 ^a	Model 1 ^a	Model 2 ^a	Model 3 ^a
NCEP ATP III criteria
No	518	285	1.00 (reference)	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	381	222	1.43 (1.07–1.91)	1.40 (1.05–1.88)	1.11 (0.80–1.53)	0.00 (–0.05–0.05)	0.00 (–0.05–0.05)	−0.05 (–0.10–0.01)
IDF criteria
No	414	220	1.00 (reference)	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	486	287	1.42 (1.08–1.88)	1.39 (1.05–1.84)	1.04 (0.75–1.46)	0.04 (–0.01–0.08)	0.03 (–0.02–0.08)	−0.01 (–0.07–0.04)
IDF/AHA criteria
No	388	201	1.00 (reference)	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	513	307	1.51 (1.15–1.99)	1.47 (1.11–1.95)	1.10 (0.79–1.55)	0.03 (–0.02–0.08)	0.03 (–0.02–0.07)	−0.03 (–0.09–0.03)
CDS criteria
No	622	336	1.00 (reference)	1.00 (reference)	1.00 (reference)	0.00 (reference)	0.00 (reference)	0.00 (reference)
Yes	274	167	1.43 (1.06–1.92)	1.38 (1.02–1.87)	1.05 (0.75–1.48)	0.03 (–0.02–0.08)	0.03 (–0.02–0.08)	−0.01 (–0.07–0.05)

Model 1 was controlled for age, sex, and education; model 2 was further controlled for ever smoking, alcohol consumption, and physical inactivity; and model 3 included all variables in model 2 plus elevated blood pressure (≥130/85 mmHg) and high fasting plasma glucose (≥5.6 mmol/L).

NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III; IDF, International Diabetes Federation; AHA, American Heart Association; CDS, Chinese Diabetes Society.

Discussion

This population-based study suggests that subclinical carotid atherosclerosis, defined as presence of carotid plaque in people without clinical CVDs, affects ∼56% of older people living in a rural area of China. Furthermore, of the individual traits of metabolic syndrome, elevated blood pressure (≥130/85 mmHg), hypertension, high FPG (≥5.6 mmol/L), and diabetes/prediabetes, but not others (e.g., obesity and dyslipidemia), are associated with an increased likelihood of having carotid plaque or increased cIMT. Finally, metabolic syndrome is associated with ∼40% increased likelihood of having carotid plaque independent of the defining criteria, driven primarily by elevated blood pressure and hyperglycemia, whereas metabolic syndrome is not associated with cIMT. Because subclinical atherosclerosis is a strong predictor of clinical CVDs, this study suggests that assessment of carotid atherosclerosis among elderly people without apparent CVDs may help to stratify risk of future cardiovascular events.

Previously, population-based studies have linked metabolic syndrome to an increased risk of clinical atherosclerotic diseases (e.g., coronary heart disease and stroke) mostly among young and middle-aged people,^3,4 although the association of CVDs with certain metabolic syndrome components (e.g., high blood pressure and high blood glucose) may be stronger than that of CVDs with metabolic syndrome as a cluster.^3,9 Indeed, the Atherosclerosis Risk in Communities study of middle-aged people suggested that, of the components of metabolic syndrome, elevated blood pressure and high blood glucose are the strongest risk traits for clinical stroke and coronary heart disease.^3,4 Similarly, the population-based Tromsø study from Norway found that metabolic syndrome, especially hypertension and impaired glucose tolerance, also were associated with markers of subclinical atherosclerosis (e.g., increased cIMT and carotid artery plaque) and progression of carotid atherosclerosis mainly in young and middle-aged people (<50 years) but not in older ages.¹⁵ It is plausible that the association between metabolic syndrome and subclinical atherosclerosis varies by age because previous research has shown that metabolic syndrome components differ between young and older adults.²⁶ Our study supports an association of metabolic syndrome with subclinical carotid atherosclerosis as measured with carotid plaque among older people, and further reveals that the association is driven primarily by elevated blood pressure and hyperglycemia. Notably, metabolic syndrome, as defined by all four sets of criteria, is rather consistently associated with an increased likelihood of having carotid plaque, which is in line with the findings from previous studies.^27,28

The Baltimore Longitudinal Study on Aging has shown that clustering of metabolic syndrome components is associated with increased cIMT and carotid artery stiffness, suggesting that traits of metabolic syndrome may interact to synergistically impact vascular thickness and stiffness.²⁹ However, other studies have suggested that metabolic syndrome as a cluster might not be superior to its individual components in addressing the risk of subclinical carotid atherosclerosis and clinical CVDs. For instance, two community-based studies of middle-aged people in China and Spain reported that, while metabolic syndrome as an entity was associated with subclinical carotid atherosclerosis, certain components of metabolic syndrome appeared to be more strongly associated with subclinical atherosclerosis than metabolic syndrome as a syndrome.^30,31 Consistent with these findings, our study suggests that, among older people without apparent CVDs, individual metabolic syndrome components, such as elevated blood pressure and hyperglycemia, could largely account for the association of metabolic syndrome with subclinical carotid plaque. These studies imply that, among the metabolic syndrome components, elevated blood pressure and high blood glucose should be the major targets for intervention against occurrence and progression of atherosclerosis.

Increased cIMT and carotid artery plaque are makers for carotid atherosclerosis that may reflect different stages and features of carotid artery atherosclerosis. Increased cIMT represents diffuse hypertensive hypertrophic response of smooth muscle cells of arteries, which indicates the early or initial stage of carotid atherosclerosis, whereas carotid plaque reflects the advanced stages of the atherosclerotic process.^15,32 The finding of an association of metabolic syndrome with carotid plaque but not with increased cIMT is consistent with the previous report.¹² However, our finding did differ from the study of Hong Kong Chinese, which showed an independent association of metabolic syndrome with increased cIMT, but no correlation between metabolic syndrome and carotid plaque.¹⁰ Different characteristics of study participants across studies may partly explain the inconsistent results. For instance, our study sample consisted of older adults without apparent CVDs, whereas the sample of Hong Kong study was much younger than ours and included all community dwellers of adults with and without clinical CVDs.

Several potential mechanisms may explain the association between metabolic syndrome and subclinical atherosclerosis in older people. First, as people age, specific clusters of metabolic syndrome traits (e.g., any combination of impaired glucose tolerance, elevated blood pressure, and high TGs) may accelerate the age-associated arterial changes.³³ The finding that the association of metabolic syndrome with subclinical atherosclerosis is driven by elevated blood pressure and plasma glucose supports the view that thickness, composition, and architecture of arterial wall and intima are determined by stresses imposed by elevated blood pressure and blood glucose.^34,35 Furthermore, the larger and more elastic arteries (e.g., carotid artery) in people with hypertension had lower arterial compliance and distensibility compared with normotensive people.³⁶ Finally, hyperglycemia could contribute to initiation and progression of atherosclerosis through multiple molecular mechanisms, such as glycosylated proteins, proinflammation, and oxidative stress.³⁵

This study included older people living in a rural community of China, to whom insufficient attention has been paid so far. In addition, a broad range of cardiometabolic risk factors were assessed and thus, we were able to define metabolic syndrome following multiple international and Chinese criteria. However, our study also has limitations. First, it is impossible to determine causality between metabolic syndrome and subclinical atherosclerosis due to the cross-sectional design. Moreover, the cross-sectional association is subject to bias owing to selective survival, which may generally lead to an underestimation of their true association, especially when metabolic syndrome and atherosclerosis are differentially associated with the survival. The CHAP cohort is currently being followed, and the follow-up data could overcome these limitations.

In conclusion, metabolic syndrome and subclinical carotid atherosclerotic plaque, as highly prevalent conditions among Chinese older people, are associated; the association is driven primarily by elevated blood pressure and hyperglycemia. These results suggest that older adults with metabolic syndrome, especially those with elevated blood pressure and hyperglycemia, even without apparent CVDs, may benefit from evaluation for subclinical atherosclerosis. This may provide an opportunity for early preventive and therapeutic intervention against the progression of atherosclerosis through appropriate management of high blood pressure and hyperglycemia.

Footnotes

Acknowledgments

We thank all study participants for their invaluable contribution to the Confucius Hometown Aging Project (CHAP) and the CHAP Study Group for their collaboration in data collection and management.

The CHAP was supported in part by grants from the Department of Science and Technology (2008GG00221), Department of Health (2009-067), and Natural Science Foundation (ZR2010HL031) of Shandong Province, China, and by the Young Scholar Grant for Strategic Research in Epidemiology at Karolinska Institutet. Dr. Qiu was supported by the Swedish Research Council and Karolinska Institutet, Stockholm, Sweden.

Author Disclosure Statement

No competing financial interests exist.

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