1. NON-INVASIVE VASCULAR IMAGING TECHNIQUES
IN CARDIOVASCULAR RISK ASSESSMENT
Rui Hu, et al.
Jinshan Hospital,
Fudan University, Shanghai, China

2. Introduction
Non-invasive imaging techniques to detect atherosclerosis have emerged as useful tools for assessing the risk of cardiovascular diseases .
Series studies present the results of two cross-sectional studies, the applications of vascular ultrasound and ophthalmoscope in assessing structure or function in macrovasculature and microvasculature.
ophthalmoscope [ɔf'θælməskəup]

3. Ultrasound examination
METHODS - Study 1
Subjects
279 pts enrolled before angigraphy
148(53%) had CAD   
10 MHz
The presence of CAD was defined as angiographic evidence of significant stenosis of any coronary artery >=50%.
Ultrasound examination
Vivid 5 Ultrasound Systems
with a 10MHz Linear Array Transducer
(GE Medical, Wisconsin, USA).
Flow mediated dilatation
Intima-Medial Thickness
All patients underwent vascular ultrasound examination before coronary angiogram.
The vascular ultrasound examinations were performed with a high resolution ultrasound system using a 10 MHz linear array transducer (Vivid 5 system, GE Medical, Wisconsin, USA).
mmIMT
FMD=100%×(D1-D0)/D0
Reprinted with permission from Sinha et al., 2002
Diameters and Blood Flow of the Brachial Artery
at Baseline and during Hyperaemia
Mean of Maximum Intima-Medial Thickness
from 12 Segments in the Carotid Arteries

4. Table 1. Clinical Characteristics of Women and Men
RESULTS
Table 1. Clinical Characteristics of Women and Men
Women
Men
P value
n=116
n=163
Age, years
63±11
61±12
0.09
Body mass index, kg/m2
26±4.0
26±3.7
0.80
Coronary artery disease, n (%)
49(42)
99(61)
0.002
Smoker, n (%)
12(10)
93(58)
<0.001
Diabetes, n (%)
40(35)
31(19)
0.005
Hypertension, n (%)
69(60)
78(48)
Hypercholesterolemia, n (%)
62(53)
88(54)
1.00
During a median follow up of 16 months, 36 patients (12.8%) experienced spontaneous cardiovascular events (cardiovascular death, acute myocardial infarction, unstable angina pectoris and congestive heart failure). The age and the impaired brachial FMD rather than the increased carotid mmIMT independently predicted the occurrence of spontaneous cardiovascular events. In patients without significant CAD, women were more likely than men to develop cardiovascular events. Therefore, endothelial function test of the brachial artery to measure FMD could be a useful tool to identify patients at risk of cardiovascular events for intensive risk factor modification and vigilant follow up, especially in women without significant CAD.
FMD, %
3.91±3.54
4.06±3.44
0.73
NMD, %
13±6.71
12±5.26
0.21
mmIMT, mm
1.05±0.32
1.13±0.40
0.051

5. Outcomes in follow-up
During a median follow up of 16 months, 36 patients (12.8%) experienced spontaneous cardiovascular events
cardiovascular death
acute myocardial infarction
unstable angina pectoris
and congestive heart failure
Events
Women
Men
P value
Non-CAD
11.9%
1.6%
0.033*
CAD
17.2%
20.4%
0.66
All pts
15.5%
11%
0.28
mmIMT<1.0mm
FMD>3.5%
Despite a significant lower prevalence of significant CAD, women had a similar incidence of spontaneous cardiovascular events as men. Furthermore, in those patients without significant CAD, women were more likely to develop cardiovascular events than men. In both men and women, impaired FMD predicted the occurrence of spontaneous cardiovascular events. Nevertheless, age but not the extent of CAD was also shown to be associated with increased risk of spontaneous cardiovascular events in women
Therewerenodifferencesintheincidenceofcardio-0.8p=0.004vasculareventsbetweenmenandwomen(11%versus15.5%,p = 0.28).InpatientswithoutCAD,femalepatients0.7
Event free survivalweremorelikelytodevelopcardiovasculareventsthanmalepatients(11.9%versus1.6%,oddsratio[OR] = 8.54,0.6p = 0.033).Femalepatientsaccountedfor8(88.9%)events
inthosepatientswithoutCAD.Incontrast,therewasnoNumber at risk Mosigni?cantdifferenceincardiovasculareventsbetweenmenNMD>12% andwomeninthosepatientswithCAD(20.4%versus17.2%,NMD12% OR = 1.24,p = 0.66).
As shown in the Women’s Ischemia Syndrome Evaluation (WISE) study [15], coronary endothelial dysfunction predicted cardiovascular events independent of cardiovascular risk factors and the severity of CAD during long-term follow-up.
P=0.098
P=0.0006
FMD<3.5%
mmIMT>1.0mm

6. Univariate Multivariate Variable HR (95% CI) P value Age, years
Table 2. Predictors of Spontaneous Cardiovascular Events by Cox Regression Model
Univariate
Multivariate
Variable
HR (95% CI)
P value
Age, years
1.06 ( )
0.001
1.05( )
0.029
Women
1.40 ( )
0.31 -
Body mass index (kg/m2)
1.01( )
0.75
Current smoker
0.70 ( )
0.27
Hypertension
0.90 ( )
Diabetes
1.23 ( )
0.57
Dyslipideamia
0.65 ( )
0.20
Extent of CAD
1.40( )
0.02
1.19( )
0.29
mmIMT mm
1.96( )
0.057
0.71( )
0.49
FMD, %
0.82( )
<0.001
0.85( )
0.012
NMD, %
0.92( )
0.99( )
0.88
FMD/NMD ratio
0.38( )
0.088
FMD>3.5%
FMD>3.5%
Nevertheless, age but not the extent of CAD was also shown to be associated with increased risk of spontaneous cardiovascular events in women. In both men and women, impaired FMD predicted the occurrence of spontaneous cardiovascular events. Nevertheless, age but not the extent of CAD was During a median follow up of 16 months, 36 patients (12.8%) experienced spontaneous cardiovascular events (cardiovascular death, acute myocardial infarction, unstable angina pectoris and congestive heart failure). The age and the impaired brachial FMD rather than the increased carotid mmIMT independently predicted the occurrence of spontaneous cardiovascular events. In patients without significant CAD, women were more likely than men to develop cardiovascular events. Therefore, endothelial function test of the brachial artery to measure FMD could be a useful tool to identify patients at risk of cardiovascular events for intensive risk factor modification and vigilant follow up, especially in women without significant CAD.
All patients were follow-up regularly in our clinic every 3-4 months, and no patient lost to follow-up. Details of subsequent spontaneous cardiovascular events including cardiovascular death, acute myocardial infarction, ischemic stroke and hospitalization for unstable angina and heart failure were recorded. Cardiovascular death was defined as death due to a myocardial or cerebral infarction or documented sudden cardiac death.
Myocardial infarction was diagnosed by the presence of at least two out of three of the following criteria: the presence of typical chest pain, a creatine kinase increment of >2 times the upper limit of normal, and new ST-segment elevation (>0.1mV) in at least 2 contiguous leads. Unstable angina pectoris was defined as hospitalization because of angina pectoris that occurred at rest and that was associated with ECG changes. Ischemic stroke was defined as clinical and radiological evidence of stroke without intracranial hemorrhage. Acute heart failure was defined as hospitalization because of the presence of signs and symptoms of congestive heart failure as modified Framingham criteria [13].
P=0.098
P=0.0006
P=0.0006
FMD<3.5%
mmIMT>1.0mm

7. Women Men Variable HR (95% CI) P value Age, years 1.09 (1.03-1.17)
Table 3 .
Gender-specific Significant Predictors of Spontaneous Cardiovascular Events
by Univariable Cox Regression Model
Women
Men
Variable
HR (95% CI)
P value
Age, years
1.09 ( )
0.005
1.04 ( )
0.066
Extent of CAD
1.26( )
0.19
1.90( )
0.033
mm IMT, mm
1.79( )
0.33
2.32( )
FMD, %
0.85( )
0.023
0.78( )
0.009
NMD, %
0.93( )
0.082
0.91( )
0.057
In both men and women, impaired FMD predicted the occurrence of spontaneous cardiovascular events. Nevertheless, age but not the extent of CAD was also shown to be associated with increased risk of spontaneous cardiovascular events in women.
In both men and women, impaired FMD predicted the occurrence of spontaneous cardiovascular events. Nevertheless, age but not the extent of CAD was also shown to be associated with increased risk of spontaneous cardiovascular events in women.

8. Overall arteriolar retinopathy 37.4%
Study 2
Recent studies suggested that arteriolar retinopathy reflected systemic microvascular disease and was associated with increased risk of cardiovascular events.
In the second cross-sectional study, the relationship between cardiovascular risk factors and arteriolar retinopathy as assessed by ophthalmoscope was investigated in 243 apparently healthy Chinese subjects during routine health checks.
Subjects
243 subjects were rolled in annual health examination;
Male/Female: 159 / 84;
Mean age ±7.9 yrs ( yrs)
Prevalence
Overall arteriolar retinopathy %
Grade 2 retinopathy %
Risk factor profiles
Male %
Smokers %
Hyperhomocysteinaemia %
Hypertension %
Overweight %
Diabetes %

9. METHODS - Study 2 Subject
243 subjects were rolled in annual health examination;
Male/Female: 159 / 84;
Mean age ±7.9 yrs ( yrs)
Prevalence
Overall arteriolar retinopathy %
Grade 2 retinopathy %
Risk factor profiles
Male %
Smokers %
Hyperhomocysteinaemia %
Hypertension %
Overweight %
Diabetes %
Smoking habits status: nonsmokers, smokers;
-Cigarette consumption= pack per day × years
-Heavy smokers: cigarette consumption ≧20 pack*yrs
-Light smokers : < 20 pack*yrs
Diagnostic criteria :
-Grade 1: Narrowing of the arteriolar lumen;
-Grade 2: Sclerosis of the adventitia and /or thickening of the arteriolar wall, visible as arteriovenous nipping
Smoking habits status: nonsmokers, smokers;
-Cigarette consumption= pack per day × years
-Heavy smokers: cigarette consumption ≧20 pack*yrs
-Light smokers : < 20 pack*yrs
Overweight : BMI ≥ 25 kg/m2
Fasting plasma tHcy level was measured by high performance
liquid chromatography (HPLC) method;
Hyperhomocysteinemia was defined as fasting plasma tHcy level ≥15.9μmol/L
The presence of arteriolar retinopathy was examined with ophthalmoscopy, and two ophthalmologists were blinded to the study
Grade 1 retinopathy
Grade 1 retinopathy
Grade 1 retinopathy
Grade 1 retinopathy
Grade 2 retinopathy

10. RESULTS
TABLE 1. Characteristics of study subjects with grade 1, grade 2
arteriolar retinopathy and without arteriolar retinopathy
Arteriolar
retinopathy Normal Grade Grade 2
n= n= n=39
Age (Yrs) ± ± 5.8*** ± 4.5 ***
BMI (Kg/m2) ± ± 2.5 * ± 2.7***
tHcy(μmol/L) ± ± ± 1.92 ***
Hypertension% *** ***
Smoker% ***

11. Interactions of plasma tHcy levels with smoking and other risk factors
Table 2 Multiple Linear Regression Model of Fasting tHcy Level
N=243, R2=22.1%
B SE(B) P
Male gender
Cigarette consumption <0.001
(Pack*yrs)
Hypertension
(Constant)
1 nonsmoker
2 light smoker
3 heavy smoker
a Dependent Variable: Hcy
b Independent variables entered: smoking consumption, male gender, and hypertension
c Excluded parameters: age, body mass index, diabetes mellitus

12. Table 3: Comparison of characteristics
of smokers and nonsmokers in male
Variables
NONSMOKER
SMOKER
N=43
N=114
Age yrs
44.9±8.7
44.1±7.6
BMI kg/m2
24.2±2.80
24.3±2.92
tHcy μmol/L
12.4±1.45
15.6 ±1.56*
SBP mmHg
118.6 ±12.2
124.0±16.6
DBP mmHg
81.9±9.51
84.0±11.1
Triglycerides mmol/L
2.44±2.51
2.18±1.24
Cholesterol mmol/L
4.60±0.87
4.59±0.70
Blood glucose mmol/L
4.99±0.74
5.05±0.78
Hyperhomocysteinaemia
14%
40.4%***
Hypertension
39.5%
40.5%
Grade 2 arteriolar retinopathy
Overall arteriolar retinopathy
9.3%
42%
26.3**
45%

13. TABLE 4. Logistic regression analysis for
predicting arteriolar retinopathy
Variables All retinopathy Grade Ⅱretinopathy
OR ( 95% CI ) OR ( 95% CI )
Age (per 10 year ) ( )*** ( )**
Male gender ( ) ( )
Overweight ( ) ( )*
Hypertension ( ) *** ( )***
Cigarette Smoking ( ) ( )*
Hyperhomocysteinaema ( ) ( )
In this study, aging, hypertension, smoking and being overweight were identified as important risk factors for the presence of arteriolar retinopathy. Smoking was also associated with an increase of homocysteine in subjects with grade II retinopathy. However, smoking rather than hyperhomocysteinemia was found to be an independent predictor for the progression of arteriolar retinopathy.
In this study, aging, hypertension, smoking and being overweight were identified as important risk factors for the presence of arteriolar retinopathy.

14. Conclusion
In conclusion, structural or functional measurement in macrovasculature and microvasculature with various non-invasive techniques could provide valuable information for the assessment of patients with cardiovascular diseases or risk factors.
In addtion, aging is an important risk factor of cardiovascular disease in both study.

15. Aging : A Global Challenge
Unprecedented
Pervasive
Enduring
Increasing burden of cardiovascular diseases globally.
Vascular disease also have become the leading causes of death among Chinese adults.
Implications in the prevention and treatment of cardiovascular disease
Coping strategy remains largely unknown
Population ageing is unprecedented, without parallel in human history—and the twenty-first century will witness even more rapid ageing than did the century just past.
Population ageing is pervasive, a global phenomenon affecting every man, woman and child—but countries are at very different stages of the process, and the pace of change differs greatly.  Countries that started the process later will have less time to adjust.
Population ageing is enduring:  we will not return to the young populations that our ancestors knew.  Population ageing has profound implications for many facets of human life.
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Yusuf S, Reddy S, Ôunpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001; 104: