Showing papers by "J. David Spence published in 2021"

Deep Learning-Based Measurement of Total Plaque Area in B-Mode Ultrasound Images

Abstract: Measurement of total-plaque-area (TPA) is important for determining long term risk for stroke and monitoring carotid plaque progression. Since delineation of carotid plaques is required, a deep learning method can provide automatic plaque segmentations and TPA measurements; however, it requires large datasets and manual annotations for training with unknown performance on new datasets. A UNet++ ensemble algorithm was proposed to segment plaques from 2D carotid ultrasound images, trained on three small datasets (n = 33, 33, 34 subjects) and tested on 44 subjects from the SPARC dataset (n = 144, London, Canada). The ensemble was also trained on the entire SPARC dataset and tested with a different dataset (n = 497, Zhongnan Hospital, China). Algorithm and manual segmentations were compared using Dice-similarity-coefficient (DSC), and TPAs were compared using the difference ( $\Delta$ TPA), Pearson correlation coefficient ( r ) and Bland-Altman analyses. Segmentation variability was determined using the intra-class correlation coefficient (ICC) and coefficient-of-variation (CoV). For 44 SPARC subjects, algorithm DSC was 83.3–85.7%, and algorithm TPAs were strongly correlated ( r = 0.985–0.988; p $^2$ using the three training datasets. Algorithm ICC for TPAs (ICC = 0.996) was similar to intra- and inter-observer manual results (ICC = 0.977, 0.995). Algorithm CoV = 6.98% for plaque areas was smaller than the inter-observer manual CoV (7.54%). For the Zhongnan dataset, DSC was 88.6% algorithm and manual TPAs were strongly correlated ( r = 0.972, p $\Delta$ TPA = −0.44 $\pm$ 4.05 mm $^2$ and ICC = 0.985. The proposed algorithm trained on small datasets and segmented a different dataset without retraining with accuracy and precision that may be useful clinically and for research.

Five-Year Outcomes of PFO Closure or Antiplatelet Therapy for Cryptogenic Stroke.

Abstract: Extended 5-Year Follow-up of the PFO Closure Trial In the initial report of the Gore REDUCE trial of patent foramen ovale closure, with a median follow-up of 3.2 years, 18 patients had stroke recur...

Deep Learning-Based Carotid Plaque Segmentation from B-Mode Ultrasound Images.

Abstract: Carotid ultrasound measurement of total plaque area (TPA) provides a method for quantifying carotid plaque burden and monitoring changes in carotid atherosclerosis in response to medical treatment. Plaque boundary segmentation is required to generate the TPA measurement; however, training of observers and manual delineation are time consuming. Thus, our objective was to develop an automated plaque segmentation method to generate TPA from longitudinal carotid ultrasound images. In this study, a deep learning-based method, modified U-Net, was used to train the segmentation model and generate TPA measurement. A total of 510 plaques from 144 patients were used in our study, where the Monte Carlo cross-validation was used by randomly splitting the data set into 2/3 and 1/3 for training and testing. Two observers were trained to manually delineate the 510 plaques separately, which were used as the ground-truth references. Two U-Net models (M1 and M2) were trained using the two different ground-truth data sets from the two observers to evaluate the accuracy, variability and sensitivity on the ground-truth data sets used for training our method. The results of the algorithm segmentations of the two models yielded strong agreement with the two manual segmentations with the Pearson correlation coefficient r = 0.989 (p

Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease.

Abstract: There are clearly sex differences in cardiovascular disease. On average, women experience cardiovascular events at an older age, and at any age, women, on average, have less atherosclerotic plaque than men. The role of the human intestinal microbiome in health and disease has garnered significant interest in recent years, and there have been indications of sex differences in the intestinal microbiome. The purpose of this narrative review was to evaluate evidence of sex differences in the interaction between the intestinal microbiome and risk factors for cardiovascular disease. Several studies have demonstrated changes in microbiota composition and metabolic profile as a function of diet, sex hormones, and host metabolism, among other factors. This dysbiosis has consequently been associated with several disease states, including atherosclerosis and cardiovascular disease. In this respect, there is a growing appreciation for the microbiota and its secreted metabolites, including trimethylamine N-oxide (TMAO), derived from intestinal bacterial metabolic pathways involving dietary choline and l-carnitine, as novel risk factors for atherosclerosis and cardiovascular outcomes. Although traditional risk factors for vascular disease have been studied broadly over the years, there exists little research to evaluate interactions of cardiovascular risk factors with a potentially sexually dimorphic intestinal microbiome. This review evaluates the role of sex differences in the composition of the intestinal microbiome, including effects of sex hormones on the microbiome, and the effects of these sex differences on cardiovascular risk factors. Diabetes and obesity exhibit sexual dimorphism, while the data concerning hypertension and dyslipidemia remain inconclusive based on the available literature. In addition, an increased proportion of gram-negative species capable of driving metabolic endotoxemia and a low-grade inflammatory response, as well as decreased numbers of butyrate-producing species, have been observed in relation to traditional vascular risk factors. In this context, circulating SCFAs and TMAO are recognized as key metabolites of the intestinal microbiome that can be readily measured in the blood for the evaluation of metabolic profile. Novel strategies focused on resolving intestinal dysbiosis as a means to slow progression of atherosclerosis and reduce the risk of cardiovascular disease should be evaluated through a lens of sex differences.

Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Clue to Metabolic Syndrome, Insulin Resistance, and Severe Atherosclerosis.

Abstract: High serum levels of triglycerides (Tg) and low levels of high-density lipoprotein cholesterol (HDL-C) are characteristic of the Metabolic Syndrome (MetS). We assessed the ratio of Tg to HDL-C as a way to identify MetS and insulin resistance. We also evaluated its association with severity of carotid atherosclerosis. Data were analyzed from three cohorts totaling 13,908 participants. MetS was defined according to the International Diabetes Federation criteria. Optimal cut-off for Tg/HDL-C ratio was obtained using Youden's index in receiver-operating characteristic (ROC) curve analyses. The risk of MetS and IR in those with a Tg/HDL-C ratio above the optimum cutoff was evaluated by logistic regression analysis. A Tg/HDL-C ratio above the optimal cutoff level significantly increased the odds ratio for MetS in the three cohorts (OR 6.00, 4.04, and 3.50, least in the healthy population), identified insulin resistance defined by the homeostatic model of insulin resistance (HOMA-IR) (p < 0.0001), and was strongly associated with atherosclerosis severity (p = 0.0001). Tg/HDL-C ratio identifies persons with MetS, insulin resistance, and severe atherosclerosis. It should be used more widely to identify patients at high risk. This is clinically important because insulin resistance is treatable.

Secular trends of ischaemic heart disease, stroke, and dementia in high-income countries from 1990 to 2017: the Global Burden of Disease Study 2017.

Abstract: Background We assessed secular trends in the burden of ischaemic heart disease (IHD), stroke, and dementia in the Organization for Economic Co-operation and Development (OECD) countries. Methods Using the Global Burden of Disease (GBD) Study 2017, we compared sex-specific and age-standardized rates of disability-adjusted life years (DALY); mortality, incidence, and prevalence of IHD and stroke; and dementia per 100,000 people, in the world, OECD countries, and Canada. Results From 1990 to 2017, the crude incidence number of IHD, stroke, and dementia increased 52%, 76%, and 113%, respectively. Likewise, the prevalence of IHD (75%), stroke (95%), and dementia (119%) increased worldwide. In addition during the study period, the crude global number of deaths of IHD increased 52%, stroke by 41%, and dementia by 146% (9, 6, and 3 million deaths in 2017, respectively). Despite an increase in the crude number of these diseases, the global age-standardized incidence rate of IHD, stroke, and dementia decreased by -27%, - 11%, and - 5%, respectively. Moreover, there was a decline in their age-standardized DALY rates (- 1.17%, - 1.32%, and - 0.23% per year, respectively) and death rates (- 1.29%, - 1.46%, and - 0.17% per year, respectively), with sharper downward trends in Canada and OECD countries. Almost all trends flattened during the last decade. Conclusions From 1990 to 2017, the age-standardized burden of IHD, stroke, and dementia decreased, more prominently in OECD countries than the world. However, their rising crude numbers mainly due to population growth and ageing require urgent identification of reversible risk and protective factors.

Stroke Prevention: Little-Known and Neglected Aspects.

Abstract: Combining available therapies has the potential to reduce the risk of stroke by 80% or more. A comprehensive review of all aspects of stroke prevention would be very lengthy; in this narrative review, we focus on some aspects of stroke prevention that are little-known and/or neglected. These include the following: (1) implementation of a Mediterranean diet; (2) B vitamins to lower homocysteine; (3) coordinated approaches to smoking cessation; (4) intensive lipid-lowering therapy; (5) lipid lowering in the elderly; (6) physiologically individualized therapy for hypertension based on renin/aldosterone phenotyping; (7) avoiding excessive blood pressure reduction in patients with stiff arteries; (8) treatment of insulin resistance with pioglitazone in stroke patients with prediabetes and diabetes; (9) impaired activation of clopidogrel in patients with variants of CYP2C19; (10) aspirin pseudoresistance due to enteric coating; (11) rationale for anticoagulation in patients with embolic stroke of unknown source; (12) pharmacologic properties of direct-acting oral anticoagulants that should be considered when choosing among them; (13) the identification of which patients with asymptomatic carotid stenosis are at a high enough risk to benefit from carotid endarterectomy or stenting; and (14) the importance of age in choosing between endarterectomy and stenting. Stroke prevention could be improved by better recognition of these issues and by implementation of the principles derived from them.

Reducing the Risk of Stroke in Patients with Impaired Renal Function: Nutritional Issues

Abstract: Patients with renal failure have extremely high cardiovascular risk; in dialysis patients the risk of stroke is increased approximately 10-fold over that in the general population. Reasons include not only a high prevalence of traditional risk factors such as diabetes, hypertension and dyslipidemia, but also the accumulation of toxic substances that are eliminated by the kidneys, so have very high levels in patients with renal failure. These include plasma total homocysteine, asymmetric dimethylarginine, thiocyanate, and toxic products of the intestinal microbiome (Gut-Derived Uremic Toxins; GDUT), which include trimethylamine N- oxide (TMAO), produced from phosphatidylcholine (largely from egg yolk) and carnitine (largely from red meat). Other GDUT are produced from amino acids, largely from meat consumption. Deficiency of vitamin B12 is very common, raises plasma tHcy, and is easily treated. However, cyanocobalamin is toxic in patients with renal failure. To reduce the risk of stroke in renal failure it is important to limit the intake of meat, avoid egg yolk, and use methylcobalamin instead of cyanocobalamin, in addition to folic acid.

Risk from low blood pressure in frail older adults: diastolic pressure and pulse pressure are important

Abstract: Blood pressure measurement with a cuff in patients with stiff arteries can be misleading, with false elevation of the diastolic pressure. Coronary flow, and most of the cerebral blood flow occur during diastole. There is a marked diastolic J curve in patients with diastolic pressure 60 mmHg. Aiming for a systolic target of 120 mmHg is not safe in some frail older patients.

Egg consumption associated with all-cause mortality in rural China: a 14-year follow-up study.

Abstract: BACKGROUND Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality. METHODS To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003-05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests. RESULTS After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants' BMI and lipid profile had no significantly difference between three egg consumption groups. BMI was 21.6±2.7 of the whole population, especially BMI>24 was only 17.3%. A bivariate association of egg consumption >6/week with increased all-cause mortality was observed compared with ≤6/week (RR: 1.35, 95% CI: 1.05, 1.73, P = 0.018). A significant interaction was observed for BMI ≥ 21.2 kg/m2 vs. BMI 6 eggs/week increased risk of all-cause mortality, even among lean participants, especially who with BMI ≥ 21.2 kg/m2. Eggs are an easily accessible and constitute an affordable food source in underdeveloped regions. Consuming <6 eggs/week may be the most suitable intake mode.

Three-dimensional ultrasound assessment of effects of therapies on carotid atherosclerosis using vessel wall thickness maps.

Abstract: We present a new method for assessing the effects of therapies on atherosclerosis, by measuring the weighted average of carotid vessel-wall-plus-plaque thickness change ( Δ V W T ¯ W e i g h t e d ) in 120 patients randomized to pomegranate juice/extract versus placebo. Three-dimensional ultrasound images were acquired at baseline and one year after. Three-dimensional VWT maps were reconstructed and then projected onto a carotid template to obtain two-dimensional VWT maps. Anatomic correspondence on the two-dimensional VWT maps was optimized to reduce misalignment for the same subject and across subjects. A weight was computed at each point on the two-dimensional VWT map to highlight anatomic locations likely to exhibit plaque progression/regression, resulting in Δ V W T ¯ W e i g h t e d for each subject. The weighted average of VWT-Change measured from the two-dimensional VWT maps with correspondence alignment ( Δ V W T ¯ W e i g h t e d , M D L ) detected a significant difference between the pomegranate and placebo groups (P = 0.008). This method improves the cost-effectiveness of proof-of-concept studies involving new therapies for atherosclerosis.

Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials.

Abstract: Background Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them. Methods Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials. Ordered categorical versions of vascular event outcomes (such as stroke and myocardial infarction) were analysed using 15 statistical techniques and their results then ranked, with the result with the smallest p-value given the smallest rank. Friedman and Duncan's multiple range tests were performed to assess differences between tests by comparing the average ranks for each statistical test. Results Data from 35 trials (254,223 participants) were shared with the collaboration. 13 trials had more than two treatment arms, resulting in 59 comparisons. Analysis approaches (Mann Whitney U, ordinal logistic regression, multiple regression, bootstrapping) that used ordinal outcome data had a smaller average rank and therefore appeared to be more efficient statistically than those that analysed the original binary outcomes. Conclusions Ordinal vascular outcome measures appear to be more efficient statistically than binary outcomes and provide information on the severity of event. We suggest a potential role for using ordinal outcomes in vascular prevention trials.

Measurement of carotid plaque burden: A tool for predicting and preventing dementia?

Abstract: Introduction Carotid plaque burden is a strong predictor of stroke risk, and preventing stroke reduces the risk of dementia. Treating carotid plaque burden markedly reduces the risk of stroke. Methods Among patients age 65–80 years attending a stroke prevention clinic, we identified those with a carotid plaque burden in the top 20% of Total Plaque Area (High TPA) and the bottom 20% (Low TPA) and performed cognitive tests: The Montreal Cognitive Assessment test (MoCA), the WAIS-III Digit Symbol-Coding Test (DSST) and Trail-Making Test (TMT) part A and B. Results There were 31 patients recruited; 11 Low TPA (5 men) and 20 High TPA (17 men), p = 0.04. TPA was 35 ± 25 mm2 in the Low TPA vs.392 ± 169 mm2 in the High TPA group (0.0001). Patients with a high plaque burden had significantly worse performance on all the cognitive tests, all p Discussion A high carotid plaque burden identifies patients at risk of cognitive impairment. Because carotid plaque burden is treatable, and treating it markedly reduces the risk of stroke, we suggest that measurement of plaque burden is a useful tool for both prediction of cognitive impairment, and prevention of dementia.