The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial.

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Left bundle branch area pacing in heart failure: A systematic review and meta-analysis with meta-regression.

INTRODUCTION: Left bundle branch area pacing is an alternative to biventricular pacing. In this study, we aim to summarize the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). OBJECTIVES: The study summarizes the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). BACKGROUND: Cardiac resynchronization therapy (CRT) reduced mortality and hospitalizations in heart failure (HF) patients with a left ventricular ejection fraction (LVEF) ≤ 35% and concomitant LBBB. Recently LBBAP has been studied as a more physiological alternative to achieve CRT. METHOD: A search of PubMed, EMBASE, and Cochrane databases were performed to identify studies examining the role of LBBAP for CRT in heart failure. Comprehensive meta-analysis version 4 was used for meta-regression to examine variables that contribute to data heterogeneity. RESULT: Eighteen studies, 17 observational and one randomized controlled trial (RCT) were examined. A total of 3906 HF patients who underwent CRT (2036 LBBAP vs. 1870 biventricular pacing [BVP]) were included. LBBAP was performed successfully in 90.4% of patients. Compared to baseline, LBBAP was associated with a reduction in QRS duration (MD: -47.23 ms 95% confidence interval [CI]: -53.45, -41.01), an increase in LVEF (MD: 15.22%, 95% CI: 13.5, 16.94), and a reduction in NYHA class (MD: -1.23, 95% CI: -1.41, -1.05). Compared to BVP, LBBAP was associated with a significant reduction in QRS duration (MD: -20.69 ms, 95% CI: -25.49, -15.88) and improvement in LVEF (MD: 4.78%, 95% CI: 3.30, 6.10). Furthermore, LBBAP was associated with a significant reduction in HF hospitalization (odds ratio [OR]: 0.44, 95% CI: 0.34, 0.56) and all-cause mortality (OR: 0.67, 95% CI: 0.52, 0.86) compared to BVP. CONCLUSION: LBBAP was associated with improved ventricular electrical synchrony compared to BVP, as well as better echocardiographic and clinical outcomes.

Interventricular Septal Involvement Is Associated with More Impaired Ventricular Function and Mechanics in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: The interventricular septum has an important role in bi-ventricular performance. We hypothesized that septal involvement in apical hypertrophic cardiomyopathy (ApHCM-Mixed) adversely impacts ventricular structure and function when compared with isolated apical hypertrophy (ApHCM-Pure). METHODS: A total of 72 patients (ApHCM-Mixed = 36, ApHCM-Pure = 36) with serial 2D and speckle-tracking echocardiographic analyses were identified. Ventricular function and mechanics were characterized by left (LV) and right (RV) ventricular global longitudinal strain (GLS), RV free wall strain, and LV myocardial work indices, and clinical events were adjudicated. RESULTS: Clinical characteristics were similar between groups (mean age, 66 ± 15 years; 49% female; LV ejection fraction, 68 ± 11%). The ApHCM-Mixed group had larger LV mass indexes (141 ± 39 vs. 111 ± 30 g/m2, p < 0.001), worse LV (-9.6 ± 3.1 vs. -14.4 ± 3.4%, p < 0.001) and RV GLS (-14.3 ± 6.7 vs. -19.2 ± 5.2%, p = 0.001), impaired RV free wall strain (-18.5 ± 7.4 vs. -22.4 ± 6.3%, p = 0.02), and lower LV myocardial work indices including global work index (938 ± 306 vs. 1272 ± 339 mmHg%, p < 0.001), when compared with the ApHCM-Pure group. At a mean follow-up of 3.9 years, these differences all persisted. Five deaths were observed, all occurring in the ApHCM-Mixed group (14% vs. 0, p = 0.05), and with four being cardiac-related. This subgroup had a mean LV ejection fraction of 63%, LV GLS of -8.7%, an LV global work index of 875 mmHg%, and RV free wall strain of -15.9%, indicating significant subclinical bi-ventricular dysfunction. CONCLUSIONS: ApHCM-Mixed represents a distinct morphology in hypertrophic cardiomyopathy associated with more impaired ventricular function and mechanics when compared with ApHCM-Pure.

Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease.

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (r=0.135; P=0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively; P<0.001) and a 2.89-fold increased risk of cardiac events (95% CI, 1.1-8.0; P=0.034). Baseline non-high-density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (r=0.35; P=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio. Conclusions Triglyceride reduction, systolic blood pressure <125 mm Hg, and non-high-density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624727.

Emerging Therapies for Recurrent Pericarditis: Interleukin-1 inhibitors.

Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis, a non-negligible group of patients will fail to achieve complete remission despite treatment and will be challenged by side effects from the chronic use of medications like corticosteroids. The cause of RP remains unknown in the majority of cases, mainly due to a gap in knowledge of its complex pathophysiology. Over the past 2 decades, the interleukin-1 (IL-1) pathway has been uncovered as a key element in the inflammatory cascade, allowing the development of pharmacological targets known as IL-1 inhibitors. This group of medications has emerged as a treatment option for patients with RP colchicine-resistance and steroid dependents. Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. Although further studies are needed to refine therapeutic protocols and taper of concomitant therapies, IL-1 inhibitors, continue to consolidate as part of the pharmacological armamentarium to manage this complex condition with potential use as monotherapy. The aim of this review is to highlight the role of IL-1 pathway in RP and discuss the efficacy, safety, and clinical applicability of IL-1 inhibitors in the treatment of RP based on current evidence.

Multimodality imaging in the diagnosis and management of prosthetic valve endocarditis: A contemporary narrative review.

Infective endocarditis is one of the leading life-threatening infections around the world. With the exponential growth in the field of transcatheter interventions and advances in specialized surgical techniques, the number of prosthetic valves and cardiac implantable devices has significantly increased. This has led to a steep rise in the number of cases of prosthetic valve endocarditis (PVE) comprising up to 30% of all cases. Clinical guidelines rely on the use of the modified Duke criteria; however, the diagnostic sensitivity of the modified Duke criteria is reduced in the context of PVE. This is in part attributed to prosthesis related artifact which greatly affects the ability of echocardiography to detect early infective changes related to PVE in certain cases. There has been increasing recognition of the roles of complementary imaging modalities and updates in international society recommendations. Prompt diagnosis and treatment can prevent the devastating consequences of this condition. Imaging modalities such as cardiac computed tomography and 18-fluorodeoxyglucose positron emission tomography/computed tomography are diagnostic tools that provide a complementary role to echocardiography in aiding diagnosis, pre-operative planning, and treatment decision-making process in these challenging cases. Understanding the strengths and limitations of these adjuvant imaging modalities is crucial for the implementation of appropriate imaging modalities in clinical practice.

Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4.

Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.

The Role of Rilonacept in Recurrent Pericarditis.

Recurrent pericarditis is associated with significant morbidity and adverse impact on quality of life. Contemporary studies have emphasized the key role of autoinflammatory pathways in its pathophysiology, mainly through the activation of inflammasomes and the production of interleukin (IL)-1α and IL-1ß. The IL-1 pathway has emerged as a promising target for the treatment of these patients. A novel IL-1 inhibitor, rilonacept, functions as an IL-1 trap binding to the circulating IL-1α and IL-1ß mitigating their inflammatory response. Recently, the RHAPSODY phase III clinical trial evaluated the use of rilonacept in patients with recurrent pericarditis, who were refractory to colchicine, or steroid-dependent. Rilonacept significantly reduced symptoms, inflammatory markers and recurrent episodes, and increased successful withdrawal of steroids. The safety profile of the medication is favourable and well tolerated by patients, with local injection site reaction being the most common side effect described. These results have shifted the paradigm of the understanding of the disease and promise to become part of the armamentarium of medications for the standard of care of these patients, with potential use as monotherapy. The changing landscape of therapeutics and pathophysiology warrants increased recognition and understanding from the international cardiology community about this novel drug and its implication in managing these complex patients.The objective of this review is to describe the bio-action of rilonacept in the treatment of recurrent pericarditis.

Transthoracic versus intra-operative transesophageal echocardiography in right heart assessment.

METHODS: Fifty-four patients who had combined mitral and tricuspid valve surgery were included. Right heart measurements were performed in the TTE apical 4-chamber (A4C) and RV inflow views, and TEE mid-esophageal 4-chamber (ME4C) and transgastric RV inflow views at end-diastole. Spearman correlation coefficients (r) were applied to test for associations between the imaging modalities. RESULTS: The mean age was 65 years and 39% were male. All patients had ≥ moderate tricuspid regurgitation (TR), and a secondary/functional etiology was present in 89%. The median TAd and RV basal (RVd) diameters in the TTE-A4C view measured 37 mm [interquartile range (IQR), 34-44] and 43 mm (IQR, 40-51), respectively. The TTE-A4C TAd strongly correlated with the TEE-ME4C measurement (r=0.72), with an overestimation of 1 mm (IQR, -2 to 4) by TEE (P<0.01). For RVd, the TTE-A4C measurement correlated moderately with the TEE-ME4C view (r=0.61), underestimating the RVd by -1 mm (IQR, -4 to 3.3) (P<0.01). No correlation was observed between TAPSE measured by TTE and TEE (r=0.22, P=0.13). CONCLUSIONS: Intra-operative TEE may reliably quantitate TA and RV size and geometry. The current findings are best interpreted as hypothesis-generating for future validative studies.

An omega-3 fatty acid plasma index ≥4% prevents progression of coronary artery plaque in patients with coronary artery disease on statin treatment.

BACKGROUND AND AIMS: Higher blood levels of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with fewer cardiovascular events and lower mortality in prospective studies. Our aim was to determine a target level of EPA and DHA to prevent progression of coronary artery plaque. METHODS: 218 subjects with stable coronary artery disease on statins were randomized to high-dose EPA and DHA (3.36 g daily) or no omega-3 for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Plasma phospholipid levels of EPA, DHA and total fatty acids were measured by gas chromatography mass spectrometry. The omega-3 fatty acid index was calculated as EPA+DHA/total fatty acid. RESULTS: Mean (SD) age was 62.9 (7.8) years; mean (SD) LDL-C level 78.6 (27.3) mg/dL and median triglyceride level 122 mg/dL. Subjects assigned to EPA and DHA had increased plasma EPA and DHA levels variably from 1.85% to 13.02%. Plasma omega-3 fatty acid index ≥4% prevented progression of fibrous, noncalcified, calcified and total plaque in nondiabetic subjects whereas those in the lowest quartile (<3.43%) had significant progression of fibrous, calcified and total plaque. No difference was observed in diabetic subjects. CONCLUSIONS: EPA and DHA added to statins prevented coronary plaque progression in nondiabetic subjects with mean LDL-C <80 mg/dL, when an omega-3 index ≥4% was achieved. Low omega-3 index <3.43% identified nondiabetic subjects at risk of coronary plaque progression despite statin therapy. These findings highlight the importance of measuring plasma levels of omega-3 fatty acids early and at trial conclusion. Targeting an omega-3 index ≥4% maximizes cardiovascular benefit.

Diastolic blood pressure predicts coronary plaque volume in patients with coronary artery disease.

BACKGROUND AND AIMS: Hypertension is associated with increased clinical and subclinical coronary artery disease (CAD); however, the relationship between blood pressure and coronary plaque volume is unclear. We examined the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on coronary artery plaque volume. METHODS: 285 subjects with stable CAD on statin therapy underwent coronary computed tomographic angiography to measure volume of fatty, fibrous, noncalcified, calcified and total coronary plaque. RESULTS: Mean (SD) age was 63.1 (7.7); mean (SD) LDL-C, 78.7 mg/dL (28.5). Compared to the highest DBP tertile (>76 mmHg), those in the lowest DBP tertile (≤68 mmHg) had lower volumes of fatty: 10.0 vs. 7.7 mm3/mm, (p trend = 0.042), fibrous: 19.6 vs. 13.8 mm3/mm (p trend = 0.011), non-calcified: 29.7 vs. 22.5 mm3/mm (p trend = 0.017) and total plaque: 37.8 vs. 25.1 mm3/mm (p trend = 0.010) whereas there was no relationship with SBP tertiles. Similarly, when examined as a continuous variable, higher DBP was a significant independent predictor of higher plaque volume after multivariate adjustment: for every 1 mmHg increase in DBP, fibrous plaque increased 0.128 mm3/mm (p = 0.022), noncalcified plaque increased 0.176 mm3/mm (p = 0.045), calcified plaque increased 0.096 mm3/mm (p = 0.001) and total plaque increased 0.249 mm3/mm (p = 0.019) whereas SBP ranging from 95 to 154 mmHg did not predict plaque volume. CONCLUSIONS: Level of DBP predicts coronary plaque with a DBP tertile ≤68 mmHg associated with the least amount of coronary plaque in subjects with LDL-C < 80 mg/dL.

The effect of eicosapentaenoic and docosahexaenoic acids on physical function, exercise, and joint replacement in patients with coronary artery disease: A secondary analysis of a randomized clinical trial.

BACKGROUND: Poor physical function impairs fitness and exercise and is associated with worse cardiovascular outcomes and all-cause mortality. Joint pain and stiffness limit physical function. OBJECTIVE: To determine if eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation improves physical function and exercise in coronary artery disease (CAD) patients. METHODS: A total of 291 subjects with stable CAD were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Change in pain, stiffness, and physical function was assessed by the Western Ontario and McMaster Universities Arthritis Index. Minutes of exercise per week were recorded, and musculoskeletal events were reported. RESULTS: Mean age (standard deviation) was 63.3 (7.6) years. In the intention-to-treat analysis, compared with controls, those on Lovaza had better physical function (mean difference, -11.0%, 95% confidence interval [CI] -18.5% to -3.5%, P = .004), better total Western Ontario and McMaster Universities Arthritis Index scores (mean difference, -9.8%, 95% CI -16.6% to -3.0%, P = .005), more exercise per week (135 minutes vs 197 minutes, respectively, P = .028), and less joint replacement (11 vs 1, respectively, P = .002). Pain and stiffness showed a trend toward significance (P = .06). The per-protocol analysis also showed less stiffness compared with controls (mean difference, -11.5%, 95% CI -22.9% to -0.1%, P = .048). CONCLUSION: High-dose EPA and DHA may benefit CAD patients by preserving physical function, increasing amount of exercise, and reducing joint replacement. EPA and DHA may be a safe preventative strategy against musculoskeletal symptoms in CAD patients.

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

BACKGROUND: Although statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume. METHODS AND RESULTS: A total of 285 subjects with stable coronary artery disease on statins were randomized to omega-3 ethyl-ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega-3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low-density lipoprotein cholesterol ≤80 mg/dL. In the intention-to-treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups (P=0.14) but approached significance in the per protocol analysis (P=0.07). When stratified by age in the intention-to-treat analysis, younger omega-3 subjects had significantly less progression of the primary endpoint, noncalcified plaque (P=0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega-3 ethyl-ester group (median % change [interquartile range], 5.0% [-5.7, 20.0] versus -0.1% [-12.3, 14.5], respectively; P=0.018). Among those on low-intensity statins, omega-3 ethyl-ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [-12.8, 9.0] versus 4.8% [-5.1, 19.0], respectively; P=0.032). In contrast, those on high-intensity statins had no difference in plaque change in either treatment arm. CONCLUSIONS: High-dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well-controlled low-density lipoprotein cholesterol levels. The benefit on low-intensity statin, but not high-intensity statin, suggests that statin intensity affects plaque volume. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727.

Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease.

BACKGROUND: Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. METHODS AND RESULTS: Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% (P<0.001) in diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase (P<0.001). Change in ACR was directly correlated with change in systolic blood pressure (r=0.394, P=0.01). CONCLUSIONS: EPA and DHA supplementation attenuated progression of albuminuria in subjects with type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727.

Ischemic stroke in a young adult with extremely elevated lipoprotein(a): A case report and review of literature.

Lipoprotein(a) [Lp(a)] is an apolipoprotein(a) molecule bound to 1 apolipoprotein B-100. Elevated levels of Lp(a) are thought to be an independent risk factor for atherosclerosis and to promote thrombosis through incompletely understood mechanisms. We report a 34-year-old man with an ischemic stroke in the setting of an extremely high Lp(a) level-212 mg/dL. He developed severe carotid artery stenosis over a 6-year period and had thrombus formation post-carotid endarterectomy. To our knowledge, this case is unique because the Lp(a) is the highest reported level in a patient without renal disease. Moreover, this is the first reported case of the youngest individual with a stroke presumably related to development of carotid plaque over a 6-year period. The thrombotic complication after endarterectomy may have been related to the prothrombotic properties of Lp(a). Of note, the Lp(a) level did not respond to atorvastatin but did decrease 15% after aspirin 325 mg was added although his Lp(a) levels were variable, and it is not clear that this was cause and effect. This case highlights the need to better understand the relation between Lp(a) and vascular disease and the need to screen family members for elevated Lp(a). We also review treatment options to lower Lp(a) and ongoing clinical trials of newer lipid-lowering drugs that can also lower Lp(a).

Parity, coronary heart disease and mortality in the old order Amish.

BACKGROUND AND AIMS: Prior data on the association between parity and mortality are limited by the presence of sociodemographic confounders including cultural norms of parity. Our objective was to determine the association between parity and mortality in the Amish, a socioeconomically homogenous group with large numbers of children per family. METHODS: We conducted a population-based cohort study among 518 Old Order Amish women enrolled in a cardiovascular awareness program. The mean length of follow-up for mortality was 13.52 years. We determined the adjusted associations between parity and obesity, prevalent coronary heart disease and mortality. RESULTS: The mean number of total births per woman was 6.7 ± 3.6 with a mode of 8. No significant association was observed between parity and all-cause mortality when adjusted for age (HR 1.00 per additional birth; 95% CI 0.96-1.05; p = 0.85) or in multivariate analysis (HR 1.00, 95% CI 0.95-1.05; p = 0.95). There was also no association of parity in age- or multivariable adjusted models with prevalent diabetes, hypertension or coronary heart disease. Despite the lack of effect of parity on mortality, a significant association of ten or more births was observed with higher body mass index (BMI) compared to the referent group of 8-9 total births. CONCLUSIONS: In a highly homogeneous population with high rates of parity, no association between overall mortality and parity was observed. Ten or more births were significantly associated with a higher BMI but not with overall mortality.

Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.

Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipid mediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animal models, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients. Those not taking Lovaza had an absence of aspirin-triggered resolvin D3 (AT-RvD3) and aspirin-triggered lipoxin B4 (AT-LXB4). Lovaza treatment restored AT-RvD3 and AT-LXB4 and gave levels of RvD6 and aspirin-triggered protectin D1 (AT-PD1) twice as high (resolvin E2 ∼5 fold) as well as lower prostaglandins. Principal component analysis indicated positive relationships for patients with CAD who were receiving Lovaza with increased AT-RvD3, RvD6, AT-PD1, and AT-LXB4 SPMs identified in Lovaza-treated patients with CAD enhanced ∼50% at 1 nM macrophage uptake of blood clots. These results indicate that patients with CAD have lower levels and/or absence of specific SPMs that were restored with Lovaza; these SPMs promote macrophage phagocytosis of blood clots. Together, they suggest that low vascular SPMs may enable progression of chronic vascular inflammation predisposing to coronary atherosclerosis and to thrombosis.-Elajami, T. K., Colas, R. A., Dalli, J., Chiang, N., Serhan, C. N., Welty, F. K. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.

Targeting inflammation in metabolic syndrome.

The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.

Resolution of NASH with weight loss documented by hepatic MRI.

A 57-year-old Asian woman with type 2 diabetes mellitus, hypertension, obesity, dyslipidaemia and history of breast cancer, was referred to the cardiovascular health and lipid centre for evaluation and management of dyslipidaemia and NASH (Non-alcoholic steatohepatitis) in 2010. She originally had a detailed work up at the liver clinic for elevated liver enzymes, with no associated symptoms. Initial hepatic MRI on 22 January 2007 showed diffuse fatty infiltration quantitated at 15%. We counselled her on lifestyle modifications, including dietary measures and exercise, geared toward weight loss. Over the next 2 years, she lost 24.5 lbs; repeat hepatic MRI on 22 December 2011 showed 6% hepatic fat, which is within the normal range. This case demonstrates the efficacy of significant weight loss in the improvement and resolution of NASH. We believe that this is the first case report documenting this through liver MRI.

Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status.

OBJECTIVE: Soy has been associated with lower risk of cardiovascular disease in Asian countries which consume daily soy. Our study examined whether production of equol, an estrogen metabolite, affected the ability of soy nuts to improve cardiovascular risk factors. MATERIALS/METHODS: Sixty postmenopausal women participated in a randomized, controlled, crossover trial of a Therapeutic Lifestyle Changes (TLC) diet alone and a TLC diet in which 0.5 cup of soy nuts (25 g of soy protein and 101 mg of aglycone isoflavones) replaced 25 g of nonsoy protein daily. Each diet was followed for 8 weeks at the end of which blood pressure (BP), lipid levels, adhesion molecules and inflammatory markers were measured. RESULTS: Women with MetS had significantly higher baseline body mass index (BMI), BP, triglycerides (TG), and soluble intercellular adhesion molecule (sICAM) than women without MetS. In women with MetS on the soy diet, significant reductions in diastolic BP (7.7%; P=0.02), TG (22.9%; P=0.02), C-reactive protein (CRP) (21.4%; P=0.01) and sICAM (7.3%; P=0.03) were noted among equol producers compared to levels on the TLC diet. No significant changes were noted in equol nonproducers. Similarly, in women without MetS, only equol producers had significant reductions in diastolic BP (3.3%, P=0.02) and CRP (30%, P=0.04). In contrast to women with MetS, TG and sICAM levels were not affected in women without MetS, a finding possibly related to lower baseline levels. CONCLUSIONS: Cardiovascular risk reduction with soy nuts is not uniform and may be greater among producers of equol.