Rachel Nicoll

Coronary and carotid atherosclerosis: Similarities and differences

Although a relationship is commonly accepted between coronary and carotid arterial disease, suggesting that atherosclerosis is a systemic condition, the extent of this association and correspondence has not been fully elucidated. This review discusses recent research in this field and highlights areas for future study. The prevalence of severe carotid stenosis increases with prevalence of coronary stenosis, with the latter being found in a significant number of stroke patients, while those with carotid stenosis may be at higher risk of myocardial infarction than stroke. There also appear to be common risk factors (age, diabetes, hypertension, smoking and dyslipidemia), although the effects in both vascular systems may not be identical. Furthermore, while the degree of stenosis in the coronary artery has little ability to predict acute coronary syndrome, which is caused by local thrombosis from a ruptured or eroded plaque, severe carotid stenosis causing hypoperfusion is highly predictive of stroke, although this effect may be time-limited. This apparent difference in event mechanism in the two arteries is interesting as is the difference in the rate of development of collaterals. Overall, the evidence shows that a clear relationship exists between disease in the coronary and carotid arteries, since conventional risk factors and the extent of stenosis and/or previous events emanating from one artery have a strong bearing on the prevalence of events in the other artery. Nevertheless, the exact correspondence between the two arteries is unclear, with sometimes contradictory study results. More research is needed to identify the full extent of risk factors for severe stenosis and cardio- or cerebral vascular events, among which, inflammatory biomarkers such as hs-CRP and prior vascular events are likely to play a key role.

Coronary and carotid atherosclerosis: How useful is the imaging?

The recent advancement of imaging modalities has made possible visualization of atherosclerosis disease in all phases of its development. Markers of subclinical atherosclerosis or even the most advanced plaque features are acquired by invasive (IVUS, OCT) and non-invasive imaging modalities (US, MRI, CTA). Determining plaques prone to rupture (vulnerable plaques) might help to identify patients at risk for myocardial infarction or stroke. The most accepted features of plaque vulnerability include: thin cap fibroatheroma, large lipid core, intimal spotty calcification, positive remodeling and intraplaque neovascularizations. Today, research is focusing on finding imaging techniques that are less invasive, less radiation and can detect most of the vulnerable plaque features. While, carotid atherosclerosis can be visualized using noninvasive imaging, such as US, MRI and CT, imaging plaque feature in coronary arteries needs invasive imaging modalities. However, atherosclerosis is a systemic disease with plaque development simultaneously in different arteries and data acquisition in carotid arteries can add useful information for prediction of coronary events.

Aggressive and diffuse coronary calcification in South Asian angina patients compared to Caucasians with similar risk factors

BACKGROUND Ethnic differences in prevalence and severity of coronary artery disease are well established and are usually attributed to risk factors variation. This study investigates the differences in coronary artery narrowing and coronary calcification between two age- and gender-matched cohorts of South Asian and Caucasian symptomatic angina patients. METHODS We identified 101 symptomatic angina patients of South Asian origin who had undergone CT angiography and calcium scoring, and compared them with 101 age and gender matched Caucasian patients. RESULTS South Asians had a greater mean number of arterial segments with both obstructive and non-obstructive plaque than Caucasians (p=0.006 and p=0.0003, respectively) and higher prevalence of triple-vessel disease (p=0.0004). Similarly, South Asians had a higher mean CAC score (p<0.0001) and the percentage of South Asians with CAC>0 and in all categories of CAC score 100-1000 were also higher, as was the number of arterial segments with calcified and non-calcified plaque. These results were more marked in patients aged >50 but in those ≤ 50, Caucasians showed a higher mean number of diseased segments (p=0.019), with non-obstructive plaque (p=0.02), possibly suggesting that Caucasians are likely to have more diffuse atherosclerosis at an earlier age. CAC prevalence and severity in this age-group were not significantly different between South Asians and Caucasians. CONCLUSION Despite similar conventional risk factors for CAD, symptomatic South Asians seem to have more aggressive and diffuse arterial calcification compared to Caucasians. These differences are more profound above the age of 50, suggesting potential genetic or other risk factors yet to be determined.

The human heart: Application of the golden ratio and angle

The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality.

A Review of the Effect of Diet on Cardiovascular Calcification

Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study ☆

AIMS In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. METHODS AND RESULTS We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.5% of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B=1.07) followed by diabetes mellitus (B=0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B=1.25), followed by male gender (B=0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC=0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC=0.81). CONCLUSION In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.

The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis

BACKGROUND Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS). METHODS AND RESULTS A meta-analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and ≥ 24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the ≥ 24 months statins group, none of the above parameters was different from controls. CONCLUSIONS Despite the consistent beneficial effect of statins on LDL-cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes.

Coronary artery calcification correlates with the presence and severity of valve calcification

AIM To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. METHODS This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. RESULTS AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. CONCLUSION The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification.

Extensive coronary calcification: a clinically unrecognised condition.

Atheroma calcification is a common feature of advanced atherosclerosis, however with the advent of CT scanning it has become possible to detect extensive coronary calcification in the absence of flow-limiting lesions. While this phenomenon is known in renal disease, it also exists in some patients with exertional angina. Vascular pathology suggests biomineralisation associated with development of osteoblast-like cells in the arterial wall. While some conventional risk factors are shared with atheroma formation, others such as ethnicity and medications appear more specific to extensive calcification and may mirror those for osteoporosis. Similarly an atherogenic diet can predispose to both conditions while some elements promote or inhibit coronary calcification but not atheroma formation. The immune and endocrine systems contribute to both conditions but not necessarily in the same way, with vitamins D and K more related to calcification than atheroma formation. Finally, statins significantly lower low density lipoprotein (LDL) cholesterol and reduce atheroma formation but are largely powerless against extensive calcification. Although investigations into the exact cause of extensive coronary calcification are in their infancy, early results suggest that it is sufficiently different in nature from atheroma formation to be considered as a separate condition. Further research would yield a greater understanding, which would aid management and the development of specific biomarkers to reduce the cost and radiation risk of CT scanning.

The acid-ash hypothesis revisited : a reassessment of the impact of dietary acidity on bone

The acid–ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid–ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.