Performance of SCORE2 and SCORE2-OP risk algorithms in a Cypriot cohort.

BACKGROUND: SCORE2 and SCORE2-OP algorithms and associated online calculators provide a new and easy method of estimating the 10-year cardiovascular risk in apparently healthy Europeans. The aim of the study was to determine the performance of these algorithms in terms of discrimination and calibration in the cohort of the Cyprus Epidemiological Study on Atherosclerosis (CESA), not only for the 10-year risk for myocardial infarction (MI), stroke and cardiovascular death, but also for all types of atherosclerotic cardiovascular events (ASCVE). METHODS: SCORE2 and SCORE2-OP for low-risk regions were calculated in a non-diabetic subset of CESA consisting of 908 people (mean age±SD: 57.8±10.5; range 40-89; 58.8% female) using baseline risk factors. Mean follow-up was 13.2±3.7 years (range 1-17) with 89 primary endpoints (MI, stroke and cardiovascular death) and 136 secondary endpoints (primary endpoints, angina, cardiac failure, coronary revascularization, transient ischemic attack, claudication and critical limb ischemia). RESULTS: The C-statistic for the prediction of the primary endpoint for all ages was 0.76 (95% CI 0.70 to 0.81) and the observed 10-year event rate was similar to the predicted one. However, the observed 10-year rate for secondary events was similar to the estimated one only when the algorithm for high-risk regions was used. CONCLUSIONS: SCORE2 and SCORE2-OP moderate risk algorithms perform well in the Cypriot population for predicting the 10-year risk for MI, stroke and fatal cardiovascular disease. However, an estimate of the 10-year risk for all ASCVD events is best calculated from the high-risk algorithm.

Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events.

BACKGROUND: Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown. OBJECTIVES: Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction. METHODS: We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE. RESULTS: Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively. CONCLUSIONS: NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort.

Measurement of blood flow in the deep veins of the lower limb using the geko™ neuromuscular electro-stimulation device.

BACKGROUND: A previous study using electrical stimulation of the common peroneal nerve (geko™) to activate the venous muscle pump measured blood flow in both the femoral and popliteal veins. Increased blood flow by as much as 60% was demonstrated in the femoral vein. Such an increase is assumed to be as a result of an increase in venous flow from the deep calf veins; however this has yet to be confirmed. The aim of this study was to conduct direct measurements in these deep calf veins to confirm this assumption in healthy individuals. METHODS: This was a single centre open-label intra-subject healthy volunteer comparison of blood flow in the peroneal, posterior tibial and gastrocnemial veins with and without the geko™ device. The device was applied to 18 volunteers. Peak venous velocity (PV) and ejected volume per individual stimulus (VS) and volume flow (VF) was determined using ultrasound. RESULTS: Peak velocity (PV) increased 216% in the peroneal vein, by 112% in the posterior tibial vein and by 137% in the gastrocnemial vein (P<0.001). Ejected volume per stimulus increased by 113% in the peroneal vein, by 38% in the posterior tibial vein and by 50% in the gastrocnemial vein (P<0.003). Associated volume flows during the muscle contraction were increased by 36%, 25% and 17%, respectively (P=0.05) CONCLUSIONS: This is the first time that neuromuscular electro-stimulation has been shown to be an effective method of increasing flow in the axial deep veins of the calf. Significant increases in velocity and volume flow in response to the electrical stimulus were seen in all three veins studied. Enhancements of both blood velocity and volume flow are key factors in the prevention of venous stasis and ultimately deep vein thrombosis (DVT). Further studies are justified to determine the efficacy of the device in the prevention of DVT.

Association of genotypes at the matrix metalloproteinase (MMP) loci with carotid IMT and presence of carotid and femoral atherosclerotic plaques.

We aimed to test the association between matrix metalloproteinase (MMP) genetic polymorphisms and (a) intima-media thickness in the common carotid (IMTcc) and (b) the presence of plaques in the carotid and femoral bifurcations. Carotid and femoral bifurcations were scanned with ultrasound in 762 Cypriot community dwellers (46% men) over the age of 40 years. IMTcc and the presence of plaques were recorded. The MMP1 1G/2G, MMP3 5A/6A, MMP7 -181A>G, MMP9 R279Q, and MMP12 -82A>G polymorphisms were determined with the TaqMan method. In men, the presence of plaques in any bifurcation was associated with the MMP9 279Q allele (OR adjusted=4.50; 95% CI=2.0 to 10.1; p<0.001) and the MMP7 -181A allele was associated with the presence of femoral plaques (OR adjusted=2.61; 95% CI=1.36 to 4.99; p=0.004). In women, the presence of femoral plaques was associated with the MMP12 -82G allele (OR adjusted=1.9; 95% CI=1.14 to 3.16; p=0.014). Our results suggest that the effect of common MMP genotypes on plaque presence may be site- and sex-dependent.

Association between presence of the metabolic syndrome and its components with carotid intima-media thickness and carotid and femoral plaque area: a population study.

BACKGROUND: We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations. METHODS: Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models. RESULTS: MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, pfor trend = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, pfor trend = 0.003) and a 14% higher SPAfem in the adjusted model. CONCLUSIONS: We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis -and by inference future cardiovascular events- associated with having less than 3 risk factors.

Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms.

OBJECTIVES: The aim was to determine the diagnostic value of a juxtaluminal black (hypoechoic) area without a visible echogenic cap (JBA) in ultrasonic images of internal carotid artery plaques. METHODS: Ultrasonic images of plaques from 324 patients with asymptomatic (n = 139) and symptomatic (n = 185) internal carotid 50% to 99% stenosis in relation to the bulb (European Carotid Surgery Trial) referred for duplex scanning were studied. The JBA in mm(2) and the gray-scale median (GSM) were obtained after image normalization. Cut-off points for GSM and JBA (combined highest sensitivity with highest specificity) were determined from receiver operator characteristic (ROC) curves. RESULTS: JBA >or= 8 mm(2) was associated with a high prevalence of symptomatic plaques in all grades of stenosis. In a multiple logistic regression model, increasing stenosis (mild, moderate, severe), GSM or= 8 mm(2) were independent predictors of the presence of hemispheric symptoms. This model could identify a high-risk group of 188 plaques that contained 142 (77%) of the 185 symptomatic plaques (odds ratio [OR], 6.7; 95% confidence interval [CI], 4.08-10.91), (P < .001), (sensitivity: 77%; specificity 66%; positive predictive value 75%; negative predictive value 68%). CONCLUSIONS: The results of this study indicate the diagnostic value and for the first time suggest a cut-off point of 8 mm(2) for JBA. This cut-off point needs to be validated in other groups and then applied to prospective studies of asymptomatic patients.

Carotid and femoral arterial wall changes and the prevalence of clinical cardiovascular disease.

The Cyprus Study is a prospective cohort study of cardiovascular disease (CVD). Its aim is to determine the relationship of intima-media thickness (IMT) of the common carotid (IMTcc), maximum thickness of IMT in the carotid bifurcation (IMTmax), number of carotid and femoral bifurcations with plaque and total plaque thickness (TPT) (sum of the maximum plaque measurements taken from the four bifurcations scanned) with the prevalence of clinical CVD. A total of 767 individuals (46% male) over the age of 40 years were recruited from a mountain village and a town outside the capital Nicosia. In addition to clinical examination, carotid and common femoral bifurcations were scanned with ultrasound. After controlling for conventional risk factors, there was little evidence of an association of IMTcc with CVD prevalence. However, IMTmax and TPT were associated with 2.9-fold (1.22 to 7.07) and 6.87-fold (2.42 to 19.43) increased odds of CVD prevalence, respectively. In conclusion, the TPT and number of bifurcations with plaque are more strongly associated with the prevalence of CVD. These findings warrant investigation in prospective studies to document associations with incident CVD events.

Serum total homocysteine, folate, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype and subclinical atherosclerosis.

OBJECTIVE: To determine the relationship of serum total homocysteine (tHcy), serum folate and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype with ultrasonic arterial wall measurements associated with subclinical atherosclerosis. STUDY DESIGN: Cross-sectional analysis of 767 participants in an ongoing prospective study. Intima-media thickness (IMT) of the common carotid (IMTcc), IMT of the internal carotid including plaque when present (IMT(max)) and the sum of the thickest plaques present in both carotid and both common femoral bifurcations (total plaque thickness (TPT)) were measured using ultrasound. RESULTS: People in the upper homocysteine quartile were more likely to have clinical cardiovascular disease (CVD) than those in the lowest three quartiles. They were also more likely to have plaques. The MTHFR 677C-->T genotype was not associated with any of the measures of subclinical atherosclerosis in either men or women but was the most important determinant of total homocysteine levels in men under 60 years of age. CONCLUSIONS: Increased homocysteine levels but not MTHFR 677C-->T genotype, are associated with subclinical atherosclerosis and the presence of plaques. Our results indicate that measurements of blood levels of homocysteine and folate in people at intermediate risk for atherosclerotic CVD before symptoms occur, might improve risk stratification and facilitate the decision to provide folate/B vitamin intervention in primary prevention.