Medical therapy for patients with subclinical and clinical carotid atherosclerosis

The management of carotid artery disease includes both modifications in life style as well treatment of vascular risk factors. However, strict risk factor modification, including improved antihypertensive therapy, lipid management, smoking cessation, and antiplatelet therapy, promise for reducing the vascular event rate in patients with carotid atherosclerosis. The best medical management for stroke prevention was highlighted in clinical practice guidelines issued jointly in 2006 by the American Heart Association and the American Stroke Association, and co-sponsored by the Council on Cardiovascular Radiology and Intervention and the American Academy of Neurology. Lowering blood pressure to a target below 120/80 mm Hg by life style interventions and antihypertensive treatment. Glucose control to near-normoglycemic levels (target hemoglobin A1C ≤7%) is recommended among diabetics to reduce micro-vascular complications and, with lesser certainty, macrovascular complications. The primary objective of this review is to summarize the current evidence and standards for the advanced diagnostic and management strategies used in asymptomatic and symptomatic patients with carotid atherosclerosis.     

Accelerated subclinical coronary atherosclerosis in patients with familial hypercholesterolemia

Objectives

We determined the extent, severity, distribution and type of coronary plaques in cardiac asymptomatic patients with familial hypercholesterolemia (FH) using computed tomography (CT).

Background

FH patients have accelerated progression of coronary artery disease (CAD) with earlier major adverse cardiac events. Non-invasive CT coronary angiography (CTCA) allows assessing the coronary plaque burden in asymptomatic patients with FH.

Materials and methods

A total of 140 asymptomatic statin treated FH patients (90 men; mean age 52 ± 8 years) underwent CT calcium scoring (Agatston) and CTCA using a Dual Source CT scanner with a clinical follow-up of 29 ± 8 months. The extent, severity (obstructive or non-obstructive plaque based on >50% or <50% lumen diameter reduction), distribution and type (calcified, non-calcified, or mixed) of coronary plaque were evaluated.

Results

The calcium score was 0 in 28 (21%) of the patients. In 16% of the patients there was no CT-evidence of any CAD while 24% had obstructive disease. In total 775 plaques were detected with CT coronary angiography, of which 11% were obstructive. Fifty four percent of all plaques were calcified, 25% non-calcified and 21% mixed. The CAD extent was related to gender, treated HDL-cholesterol and treated LDL-cholesterol levels. There was a low incidence of cardiac events and no cardiac death occurred during follow-up.

Conclusion

Development of CAD is accelerated in intensively treated male and female FH patients. The extent of CAD is related to gender and cholesterol levels and ranges from absence of plaque in one out of 6 patients to extensive CAD with plaque causing >50% lumen obstruction in almost a quarter of patients with FH.     

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.     

Evaluation of subclinical atherosclerosis in Egyptian psoriatic patients

BackgroundPsoriasis (Ps) is a common, relapsing, immune-mediated, inflammatory skin disorder of unknown etiology. Ps is not single organ disease confined to the skin but it is systematic inflammatory condition analogous to other inflammatory immune disorders which are known to have increased risk of heart disease. On other hand, inflammation plays also an important role in the pathogenesis of atherosclerosis. So, there is striking similarity between molecular and inflammatory pathway in Ps and atherosclerosis.Aim of the workWas to assess the presence of subclinical atherosclerosis in patients with Ps by using carotid ultrasonography.Patients and Methods60 patients with Ps were enrolled in this study after exclusion of traditional cardiovascular risk factors and cardiovascular diseases (CVD). In addition, 20 age and gender matched healthy persons served as controls. Patients were classified according to Ps area and severity index (PASI) score into group I (20 mild patients), group II (20 moderate) and group III (20 severe). The average common carotid artery (CCA) intima media thickness (IMT), internal diameter (ID) and arterial wall mass index (AWMI) were measured using high resolution B- mode ultrasound.ResultsPsoriatic patients showed statistically significant increase in CCA-IMT (P value 0.001), AWMI (P value 0.010) and significant decrease in ID (P value 0.001), as compared to controls.ConclusionPsoriasis patients could be suggested as a group with an increased atherosclerotic risk especially in older ages with longer duration of Ps. The carotid IMT, ID and AWMI can identify patients with subclinical atherosclerosis who need special follow up to reduce cardiovascular morbidity and mortality.     

Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification

This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S(3) gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol > or =130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.     

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus

OBJECTIVE: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.     

Potential role of high sensitivity cardiac troponin T in subclinical coronary atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo determine the role of high sensitivity cardiac troponin T (HS cTnT) in subclinical coronary atherosclerosis in SLE patients at an apparent low risk for CVD according to traditional risk factors.Patients and methodsThe presence of subclinical coronary atherosclerosis was assessed by non-contract coronary computerized tomography and calcium score was measured using Agatston score in 30 SLE patients asymptomatic for CVD and 30 age and sex matched apparently healthy controls. SLE disease activity index (SLEDAI) was assessed. Serum HScTnT concentration was measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean age of the patients was 33 ± 5.7 years, disease duration of 33.7 ± 22 months and mean SLEDAI 8.1 ± 5.02. The mean HS cTnT level was 12.8 ± 11.3 ng/L (1–36 ng/L). Their Framingham score was 4.8 ± 3.1 (1–12). Framingham score was low in both SLE patients (range 1–12%) and controls (1–9%) (p = 0.12). 11 (36.7%) patients, but none of the controls, had coronary artery calcification (CAC). Serum HScTnT concentration was detectable (>3 ng/L) in 16 (53.3%) patients and 2 (6.7%) control (p < 0.001). Interestingly, it was detectable in all patients with CAC, but in only 26.3% of patients without (p < 0.001). HScTnT significantly correlated with Agatston (r = 0.63, p = 0.04), with erythrocyte sedimentation rate (r = ?0.65, p = 0.03), and with C-reactive protein (r = 0.76, p = 0.03) in SLE patients with CAC.ConclusionSerum HScTnT level is high and associated with CAC in SLE patients who are at an apparently low risk for CVD according to the Framingham risk score. HS cTnT may be a useful biomarker for SLE-associated subclinical atherosclerosis.     

Factors associated with accelerated subclinical atherosclerosis in patients with spondyloarthritis without overt cardiovascular disease

Data on the progression of atherosclerosis in spondyloarthritis (SpA) are scarce, despite a high burden of cardiovascular diseases (CVD). The aim of this study was to identify the predictors of an accelerated subclinical atherosclerosis in patients with SpA. Study participants were 66 patients free of CVD classified according to ASAS criteria. The patients were evaluated at baseline and after 13.5 ± 3.6 months. Ultrasound measurements of carotid intima-media thickness (cIMT) and distensibility coefficient (cDC) were used to assess the extent of subclinical atherosclerosis. cIMT progression rate was calculated dividing the cIMT change by the time between the scans. Accelerated atherosclerosis was defined as the top cIMT progression rate quartile. At baseline, the mean Framingham Risk Score was 14 ± 11%. At follow-up, cIMT increased in 39 patients (59%; mean difference 0.01 ± 0.10; p = 0.334). Mean cIMT progression rate was 0.01 mm/year (95% CI ? 0.02 to 0.03). cDC was unchanged at follow-up. Patients with accelerated atherosclerosis (n = 16) had significantly higher serum creatinine and lower glomerular filtration rate (eGFR) at baseline. In multiple logistic regression, only eGFR and the presence of syndesmophytes were associated with an accelerated atherosclerosis, independent of traditional cardiovascular risk factors. In patients with SpA without overt CV disease, a decrease in renal function and radiographic damage are conditions associated with the development of subclinical accelerated atherosclerosis. Longitudinal assessment of cIMT could be useful to better evaluate the individual CV risk of these patients improving their prognostic stratification.     

Association between depression and subclinical carotid atherosclerosis in patients with Type 1 diabetes

Aims Recent studies have suggested an association between depression and subclinical atherosclerosis as measured by presence of carotid atherosclerotic plaque and increased intima‐media thickening in non‐clinical populations. Given the high prevalence of depression in patients with Type 1 diabetes and the diabetes‐related risk factors for atherosclerosis, we hypothesized that this relation might also be of special relevance in Type 1 diabetic patients. Methods Intima‐media thickness (IMT) and the presence of plaques in the carotid arteries were quantitatively assessed by high‐resolution ultrasound in 175 adults (89 men, 86 women) with an established diagnosis of Type 1 diabetes. Having been treated for depression or current Beck Depression Inventory scores > 10 were considered to indicate depression. Results In men, the risk of plaque was higher in depressed subjects relative to non‐depressed participants after adjustment for age, smoking status, systolic blood pressure, dyslipidaemia and body mass index [odds ratio (OR) 5.19; 95% confidence interval (CI) 1.29, 20.81]. Depressed women did not have an increased risk of plaque compared with non‐depressed women (OR 0.97; 95% 95% CI 0.22, 4.34). We did not observe an association between depression and IMT, in men or in women. Conclusions In line with previous research, our findings suggest a link between depression and subclinical atherosclerosis in Type 1 diabetic men, but not in women.     

The predictive role of C-reactive protein in patients with hypertension and subclinical atherosclerosis

Background: Recent guidelines published by the joint European Society of Hypertension/European Society of Cardiology have suggested the inclusion of C-reactive protein (CRP) in the standard assessment of cardiovascular risk in hypertensive patients, but few data are available on the role of CRP in patients with carotid lesions.
Methods: We studied 472 patients, 236 with and 236 without hypertension, sex- and age-matched, with and without early stages of atherosclerosis (e.g. those with an asymptomatic intima–media thickness of >0.9 mm), the influence of all the other traditional cardiovascular risk factors (e.g. older age, male sex, obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidaemia) and of high-sensitivity CRP levels on cerebrovascular and cardiovascular events in a 5-year follow up.
Results: At the end of follow up, patients with hypertension had more events than those without (25% vs 17%, P < 0.05). Proportional hazard analysis revealed in the group of patients without hypertension the presence of baseline carotid lesions ( P = 0.02) as predictor of events. In patients with hypertension, the presence of baseline carotid lesions ( P = 0.04) and elevated CRP levels ( P = 0.02) predicted clinical events. Patients with hypertension also showed a significant relationship between clinical events and quintiles of CRP levels ( P < 0.01).
Conclusion: Beyond the utility of high-sensitivity CRP levels in the prediction of early and late stages of atherosclerosis and subsequently on its association with clinical events, the therapeutic implications of these results remain to be evaluated by further studies.     

Measurement of subclinical carotid atherosclerosis may help in predicting risk for stroke in patients with diabetes

Diabetes is one of the most important risk factor for stroke and cardiovascular disease (CVD), especially in young patients. The control of classical vascular risk factors failed in terms of prevention of stroke in patients with diabetes. In addiction, in these patients the glycemic control showed a benefit on microvascular disease but lacked an established benefit in macrovascular disease. Therefore, implementations of effective stroke prevention strategies appear necessary in patients with diabetes. Ultrasound surrogate or intermediate markers of carotid atherosclerosis include carotid intima-media thickness (cIMT), carotid plaque (CP), and carotid stiffness (STIFF) have been demonstrated to increase in patients with diabetes and to be able to predict risk for stroke. In this editorial we discuss the opportunity to prevent the onset of vascular disease in their “preclinical or subclinical” stage in patients with higher risk for stroke such as diabetic patients.     

Alcohol intake is not associated with subclinical coronary atherosclerosis

Background

The inverse relation between alcohol intake and clinical coronary artery disease (CAD) is well established, although the mechanisms remain speculative. We studied the relation between alcohol intake and subclinical CAD to assess the possible role of alcohol in atherogenesis.

Methods

We conducted a prospective study of 731 consecutive, consenting, active-duty US Army personnel (39 to 45 years of age) without known CAD who were undergoing a routine physical examination. Each participant was surveyed with the validated Block dietary questionnaire, which included detailed information on alcohol intake as wine, beer, or liquor. Subclinical CAD was determined by means of electron beam computed tomography to quantify coronary artery calcification (CAC).

Results

The mean age was 42 (±2); 83% were male, 71% were white, and 82% were college graduates. The prevalence of CAC was 18.6% (mean CAC score = 12 ± 69). Twenty-two percent drank alcohol daily, with an average of 2.4 drinks per day. Systolic blood pressure was correlated with number of drinks per day (r = 0.10, P = .025). Among drinkers, HDL was weakly correlated with daily alcohol consumption (r = 0.10, P = .025). There was no relation between the CAC score and the alcohol intake as measured by drinks per day (OR, 1.02; 95% CI, 0.64 to 1.63; 1.13, 0.59 to 2.15; 1.26, 0.69 to 2.59, for less than 1, 1 to 2, and more than 2 drinks per day, respectively). Stratified analyses based on type of alcohol and multivariate analyses indicated no independent relation between any type or quantity of alcohol intake and the presence or extent of coronary calcification.

Conclusions

Alcohol intake does not appear to be inversely related to subclinical CAC, implying that previous observations of a protective effect of alcohol on clinical CAD may involve factors related to plaque stability rather than atherogenesis.