Cardiovascular diseases have been identified as "public health enemy no. 1" by the World Health Organization.
Cardiovascular diseases kill more people than any other single disease.
The search for reliable preventive methods should be pursued.

Vulnerable or unstable plaque screening and risk prediction.

Weekly overview on new findings and reviews.

Do coronary high-intensity plaques by non-contrast T1-weighted imaging (T1WI) represent a novel predictive factor?
How to identify by non-invasive imaging patients with a high risk of coronary events? Noguchi et al. showed already in 2011 that
the presence of high-intensity plaques (HIP) in the carotid artery is associated with an increased risk of coronary events. In a follow-up study by Noguchi et al., this technique was used in 568 patients with suspected or known coronary artery disease (CAD) who underwent non-contrast T1WI to determine the plaque to myocardium signal intensity ratio (PMR). A regression analysis identified the presence of PMR≥1.4 plaques as the significant independent predictor of coronary events (hazard ratio 3.96; p<0.001) compared with the presence of CAD (HR, 3.56; p<0.001) and other traditional risk factors. Noguchi et al. concluded that  HIPs which can be identified in a non-invasive, quantitative manner are significantly associated with coronary events, and may thus represent a novel predictive factor.

J Am Coll Cardiol. 2013 Dec 14. pii: S0735-1097(13)06479-6. doi: 10.1016/j.jacc.2013.11.034. [Epub ahead of print]
High-Intensity Signals in Coronary Plaques on Non-contrast T1-Weighted Magnetic Resonance Imaging as a Novel Determinant of Coronary Events.
Noguchi T(1), Kawasaki T(2), Tanaka A(3), Yasuda S(4), Goto Y(4), Ishihara M(4), Nishimura K(5), Miyamoto Y(5), Node K(3), Koga N(2).
(1)Department of Cardiovascular Medicine and. Electronic (2)Cardiovascular Center, Shin-Koga Hospital, Kurume, Japan.
(3)Department of Cardiovascular Medicine, Saga University, Saga, Japan. (4)Department of Cardiovascular Medicine and. (5)Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Suita, Japan.

OBJECTIVES: We wished to determine whether coronary high-intensity plaques (HIPs) visualized by non-contrast T1-weighted imaging (T1WI) can predict future coronary
events.  BACKGROUND: Coronary HIPs are associated with characteristics of vulnerable plaques including positive remodeling, lower Hounsfield units, and
ultrasound attenuation. However, it remains unclear whether the presence of HIPs is associated with an increased risk of coronary events.
METHODS: We prospectively examined the signal intensity of coronary plaques in 568 patients with suspected or known coronary artery disease (CAD) who underwent
non-contrast T1WI to determine the plaque to myocardium signal intensity ratio (PMR). RESULTS: During the follow-up period (median, 55 months), coronary events were
observed in 55 patients. Receiver operating characteristic curve analysis identified a PMR of 1.4 as the optimal cutoff for predicting prognosis. Multivariate Cox regression analysis identified the presence of PMR≥1.4 plaques as the significant independent predictor of coronary events (hazard ratio [HR], 3.96; 95% confidence interval [CI], 1.92 to 8.17; p<0.001) compared with the presence of CAD (HR, 3.56; 95%CI, 1.76 to 7.20; p<0.001) and other traditional risk factors. Among the 4 groups based on the PMR cutoff and presence of CAD, coronary event-free survival was lowest in the PMR≥1.4+CAD group and highest in the PMR<1.4+no CAD group. Importantly, the PMR≥1.4+no CAD group had an intermediate rate of coronary events, similar to the PMR<1.4+CAD group. Conclusions: HIPs identified in a non-invasive, quantitative manner are
significantly associated with coronary events, and may thus represent a novel predictive factor.

Should erectile dysfunction (ED) be a routine question in any risk calculator

Organic erectile dysfunction (ED) is common in men with established coronary artery disease (CAD). An important contributor is endothelial dysfunction which affects various vascular beds and is involved also in the development of coronary atherosclerosisEndothelial dysfunction is characterized by a reduction in endogenous nitric oxide (NO) activity which can be attributed to an elevation in asymmetric dimethylarginine levels. Erectile function positively correlated with coronary endothelial function which was independent of age, body mass index, smoking status, high-density lipoprotein, C-reactive protein and insulin resistance index. In a prospective study, Jackson showed that in men with organic erectile dysfunction the multi-detector cardiac computed tomography (MDCT) was normal in only 5 out of 65 men. CT calcium was present in 53 men. However, the exercise ECG was borderline abnormal in only 3 men. Jackson concluded that erectile dysfunction may predict CAD in the absence of cardiac symptoms. Furthermore, MDCT detects subclinical plaque which may be vulnerable to rupture and which is not flow limiting enough to influence the exercise ECG. The window of 2-5 years between erectile dysfunction and a CAD event offers an opportunity for aggressive risk factor reduction. Erectile dysfunction should be a routine question in any risk calculator. 

Int J Clin Pract. 2013 Aug 25. doi: 10.1111/ijcp.12275. [Epub ahead of print]
Erectile dysfunction and asymptomatic coronary artery disease: frequently detected by computed tomography coronary angiography but not by exercise
Jackson G.
London Bridge Hospital, London, UK; Guy's and St Thomas' Hospitals NHS Trust, London, UK.

Cardiac computed tomography angiography
(CCTA) in coronary artery disease (CAD): useful for long-term prognosis?

Computed tomography (CT scanning of the heart, CT coronary angiogram) or cardiac computed tomography angiography (CCTA) is used to examine occlusion in coronary arteries. Although not routinely used in clinical practice, it provides important prognostic information. CCTA permits visualization of the vessel wall which has a crucial role in the development of the acute coronary syndrome. It was concluded that this tool may improve risk stratification in patients. Hadamitzky et al. provided in their study long-term follow-up (5.6 years) data on prognosis: The severity of coronary artery disease (CAD) and the total plaque score were the best predictors of death and non-fatal myocardial infarction. The annual event rate ranged from 0.24% for patients with no CAD to 1.1% for patients with obstructive CAD and 1.5% for patients with CAD and extensive plaque load. Hadamitzky et al. concluded that CCTA imaging may be a valuable tool in the assessment of long-term prognosis in patients with suspected CAD.

Eur Heart J. 2013 Sep 24. [Epub ahead of print]
Prognostic value of coronary computed tomography angiography during 5 years of follow-up in patients with suspected coronary artery disease.
Hadamitzky M, Täubert S, Deseive S, Byrne RA, Martinoff S, Schömig A, Hausleiter J.
Institut für Radiologie und Nuklearmedizin, Deutsches Herzzentrum München, Technische Universität München, Lazarettstrasse 36, 80636 Munich, Germany.

Magnetic resonance detected plaque hemorrhage in carotid plaques: association with inflammatory features?

Magnetic resonance imaging (MRI) can detect hemorrhage in carotid plaques which is associated with a higher risk of cerebrovascular events. Is plaque hemorrhage also associated with infiltration of inflammatory cells? Altaf et al. provide evidence that indeed links exist between hemorrhage and inflammatory infiltration: The MRI positive plaques were associated with histologic evidence of plaque hemorrhage, high lipid proportion, and low fibrous content. They also had higher levels of macrophage and lymphoid cells compared with MRI negative plaques. MRI positive plaques were also more likely to be graded as unstable based on morphology and cellular composition. It was concluded by Altaf et al. that the relationship between inflammation and instability of plaques may explain the increased risk associated with MRI positive plaques.

Ann Vasc Surg. 2013 Jul;27(5):655-61. doi: 10.1016/j.avsg.2012.10.011. Epub 2013 Mar 26.
Magnetic resonance detected carotid plaque hemorrhage is associated with inflammatory features in symptomatic carotid plaques.
Altaf N, Akwei S, Auer DP, MacSweeney ST, Lowe J.
Department of Vascular and Endovascular Surgery, Queens Medical Centre, Nottingham, UK.

MRI imaging of carotid plaques: can future cerebral ischemia be predicted?

Methods are needed that can identify vulnerable plaques. In case of carotid artery stenosis, vulnerable plaques are expected to be associated with an increased risk of cerebral events. Esposito-Bauer et al. show that MRI plaque imaging has indeed the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. Event-free survival was higher among patients with the MRI-defined stable lesion types. It was concluded that MRI could improve selection criteria for invasive therapy in the future. 

PLoS One. 2013 Jul 24;8(7):e67927. doi: 10.1371/journal.pone.0067927. Print 2013.
MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.
Esposito-Bauer L, Saam T, Ghodrati I, Pelisek J, Heider P, Bauer M, Wolf P, Bockelbrink A, Feurer R, Sepp D, Winkler C, Zepper P, Boeckh-Behrens T,
Riemenschneider M, Hemmer B, Poppert H.
Department of Neurology, Technische Universität München, Munich, Germany; Department of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes,
Homburg, Germany.

High C-reactive protein: are increased adverse cardiovascular events just a consequence of ongoing coronary narrowing?
C-reactive protein (CRP) is used as a marker of systemic inflammation that can increase up to 50 thousand fold in acute infection. It remains, however, unclear to what extent CRP is involved in ongoing atherosclerosis. The study of Patel et al. provides evidence that coronary narrowing is not monitored by CRP in postmenopausal women. However, adverse cardiovascular events are increased among patients with higher CRP levels.

Clin Cardiol. 2013 Jun 10. doi: 10.1002/clc.22155. [Epub ahead of print]
Discordant Association of C-Reactive Protein With Clinical Events and Coronary Luminal Narrowing in Postmenopausal Women: Data From the Women's Angiographic
Vitamin and Estrogen (WAVE) Study.
Patel D, Jhamnani S, Ahmad S, Silverman A, Lindsay J.

Department of Internal Medicine, Washington Hospital Center, Washington, DC; Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth
University Hospital, Richmond, Virginia.

Is a stable plaque turned into a vulnerable plaque by cardiac dilatation?
Although great progress has been made in the prevention of myocardial infarction, mechanisms predisposing to plaque rupture remain greatly unresolved. In case that mechanisms hve been identified, they are often inadequately treated. As discussed previously, increased pulse pressure which raises shear stress increases the vulnerability of a plaque. It is in this context an important observation by Burgmaier et al. that left ventricular dilation which is known to be associated with an increase in overall wall stress (for an overview, see heartimaging) is associated with decreased fibrous cap thickness of coronary lesions. Enddiastolic volume predicted plaque vulnerability and it was concluded that this parameter may be a useful adjunct to the risk-stratification of patients with type 2 diabetes. It can be inferred that an increase in wall stress underlies the relationship between
chamber dilation and plaque vulnerability. A raised wall stress of the myocardial wall is expected to be transmitted to plaques leading to plaque cap thinning. One of the conclusions is that factors promoting chamber dilatation should be identified and treated more rigorously. For a potential target, see HUFA deficiency found in dilative heart failure requiring replacement of HUFAs.

Cardiovasc Diabetol. 2013 Jul 11;12(1):102. [Epub ahead of print]
Plaque vulnerability of coronary artery lesions is related to left ventricular dilatation as determined by optical coherence tomography and cardiac magnetic
resonance imaging in patients with type 2 diabetes.
Burgmaier M, Frick M, Liberman A, Battermann S, Hellmich M, Lehmacher W, Jaskolka A, Marx N, Reith S.

Coronary calcium: a marker of atherosclerosis and of plaque vulnerability?

Calcification of coronary plaques is thought to contribute to their instability. The study of Servadei et al. indicates that coronary artery calcium can define the risk of acute coronary events but surprisingly does not identify the vulnerable plaque. Clearly more research is needed to unravel adverse molecular mechanisms associated with coronary calcium:

Atherosclerosis. 2013;229:124-9.
Coronary calcification identifies the vulnerable patient rather than the vulnerable Plaque.
Mauriello A, Servadei F, Zoccai GB, Giacobbi E, Anemona L, Bonanno E, Casella S.
Anatomic Pathology, University of Rome Tor Vergata, Italy.

The vulnerable plaque: another reason why high pulse pressure is detrimental?
Plaques are exposed to shear stress of the flowing blood which can be crucial for the rupture of a vulnerable plaque. One might, therefore, expect, that increased pulse pressure, i.e. high systolic and low diastolic blood pressure due to adverse vascular remodeling that involves also large arteries contributes to plaque rupture. In the study of Selwaness et al. it is indeed shown that pulse pressure is the strongest determinant of intraplaque hemorrhage which is associated with ischemic stroke. The combination of systolic hypertension and smoking was associated with 2.5 times increased risk of intraplaque hemorrhage:

Hypertension. 2013;61:76-81.
Blood pressure parameters and carotid intraplaque hemorrhage as measured by magnetic resonance imaging: The Rotterdam Study.
Selwaness M, van den Bouwhuijsen QJ, Verwoert GC, Dehghan A, Mattace-Raso FU, Vernooij M, Franco OH, Hofman A, van der Lugt A, Wentzel JJ, Witteman JC.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Prediction of inflamed plaques by FDG-PET?

How to predict a high risk of ischemic stroke? How to identify vulnerable plaques? It might not be surprising that techniques that use information from the altered metabolism of inflamed plaque provide such information. In the study by Saito et al. it is shown that fluorodeoxyglucose (FDG) positron emission tomography (PET) can indeed predict the lipid-rich and inflamed plaque:

Cerebrovasc Dis. 2013;35:370-7.
Validity of Dual MRI and F-FDG PET Imaging in Predicting Vulnerable and Inflamed Carotid Plaque.
Saito H, Kuroda S, Hirata K, Magota K, Shiga T, Tamaki N, Yoshida D, Terae S, Nakayama N, Houkin K.
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Plaque volume as risk predictor?

It remains a great challenge to rate cardiovascular risk during progression of atherosclerosis. While various methods have emerged for monitoring subclinical atherosclerosis ranging from measurement of intima-media thickness to arterial stiffness and flow-mediated vasodilatation, the transition from stable to vulnerable plaque remains greatly unexplored. In the prospective study of Wannarong et al. it is shown that total plaque volume is superior in predicting cardiovascular events compared with intima-media thickness and total plaque area:

Stroke. 2013 Jun 4. [Epub ahead of print]
Progression of Carotid Plaque Volume Predicts Cardiovascular Events.
Wannarong T, Parraga G, Buchanan D, Fenster A, House AA, Hackam DG, Spence JD.
From the Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute (T.W., D.G.H., J.D.S.), Imaging Research Group, Robarts Research Institute (G.P., D.B., A.F., J.D.S.), Department of Medicine (A.A.H., D.G.H.), and Department of Epidemiology and Biostatistics (D.G.H.), Western University, London, Canada; and Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (T.W.).

21.12.2013 (HR)