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Mechanical circulatory support with durable continuous-flow ventricular assist devices has become an important therapeutic management strategy for patients with advanced heart failure. As more patients have received these devices and the duration of support per patient has increased, the postimplantation complications have become more apparent, and the need for approaches to manage these complications has become more compelling. Continuous-flow ventricular assist devices, including axial-flow and centrifugal-flow pumps, are the most commonly used mechanical circulatory support devices. Continuous-flow ventricular assist devices and the native heart have a constant physiological interplay dependent on pump speed that affects pressure-flow relationships and patient hemodynamics. A major postimplantation complication is cerebrovascular vascular accidents. The causes of cerebrovascular vascular accidents in ventricular assist device recipients may be related to hypertension, thromboembolic events, bleeding from anticoagulation, or some combination of these. The most readily identifiable and preventable cause is hypertension. Hypertension management in these patients has been hampered by the fact that it is difficult to accurately measure blood pressure because these ventricular assist devices have continuous flow and are often not pulsatile. Mean arterial pressures have to be identified by Doppler or oscillometric cuff and treated. Although guidelines for hypertension management after ventricular assist device implantation are based largely on expert consensus and conventional wisdom, the mainstay of treatment for hypertension includes guideline-directed medical therapy for heart failure with reduced ejection fraction because this may reduce adverse effects associated with hypertension and increase the likelihood of favorable ventricular remodeling. The use of systemic anticoagulation in ventricular assist device recipients may at a given blood pressure increase the risk of stroke.

Background Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention. Design and method This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.4% females and mean BMI 26.6 ± 3.7 SD. Data were collected through a screening campaign in rural area of Kirehe District, Eastern of Rwanda, with the objective to characterize and examine the prevalence of elevated blood pressure (BP) and other CVD risk factors. An adapted tool from the World Health Organization STEPwise Approach was used for data collection. Elevated BP was defined as ≥ 140/90 mm/Hg and elevated blood glucose as blood glucose ≥ 100 mg/dL after a 6-h fast. Results Of the sampled population, 21.2% (n = 910) had an elevated BP at screening; BP was elevated among individuals not previously known to have HTN in 18.7% (n = 752). Among individuals with a prior diagnosis of HTN, 62.2% (n = 158 of 254) BP was uncontrolled. Age, weight, smoking, alcohol history and waist circumference were associated with BP in both univariate analyses and multivariate analysis. Conclusion High rates of elevated BP identified through a health screening campaign in this Rwandan district were surprising given the rural characteristics of the district and relatively low population age. These data highlight the need to implement an adequate strategy for the prevention, diagnosis, and control of HTN that includes rural areas of Rwanda as part of a multicomponent strategy for CVD prevention.

Objective The extent to which infertility and pregnancy independently increase risk of diabetes and subclinical atherosclerosis is not known. Research Design And Methods We conducted a secondary analysis of Diabetes Prevention Program (DPP) and the DPP Outcomes Study over a 15-year period. We included women who answered questions about gravidity and infertility at baseline (n = 2085). Infertility was defined as > 1 year of unsuccessful attempts to conceive; thus, women could have histories of infertility as well as pregnancy. Risk of diabetes associated with gravidity and infertility was calculated using Cox proportional hazards models adjusting for age, race/ethnicity, treatment arm, body mass index, and pregnancy during the study. Among women who underwent assessment of coronary artery calcification (CAC) (n = 1337), odds of CAC were calculated using logistic regression models with similar covariates. Results Among premenopausal women (n = 1075), women with histories of pregnancy and infertility (n = 147; hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.30, 2.49) and women with histories of pregnancy without infertility (n = 736; HR 1.49; 95% CI 1.15, 1.93) had greater diabetes risk than nulligravid women without infertility (n = 173). Premenopausal nulligravid women with histories of infertility had a non-significant elevation in risk, although the number of these women was small (n = 19; HR 1.63; 95% CI 0.88, 3.03). Associations were not observed among postmenopausal women (n = 1010). No associations were observed between infertility or pregnancy with CAC. Conclusions Pregnancy, particularly combined with a history of infertility, confers increased risk of diabetes but not CAC among glucose-intolerant premenopausal women.

Subclinical markers of atherosclerosis, including CAC, are less favorable in adults with IGT. In previous adult studies, higher PA has been associated with lower CAC with findings varying by age and sex. PA and CAC were examined by age and sex in the diverse Diabetes Prevention Program Outcomes Study (DPPOS) cohort with IGT who were randomized at baseline to lifestyle intervention, metformin, or placebo groups for a mean of 3.2 years, and subsequently observed in DPPOS for follow-up. PA was measured via questionnaire (annually); accelerometry once at 11-13yrs and CAC Agatston score (AS) using chest computed tomography at 13-15 yrs from randomization. The relationship between PA and CAC was examined using Tobit regression models in 1434 participants with valid PA and CAC data (mean age 63±9.5 yrs; 70% female; 54% with diabetes) adjusted for treatment group, age, sex, race/ethnicity, lipid medication use, diabetes status, and cumulative metformin exposure; pairwise and three-way interactions were examined. Accelerometry-assessed median (IQR) daily step counts and moderate+ PA (MVPA) minutes were 5302 (3576, 7104) and 21 (9, 41), respectively. Median (IQR) AS was 9 (0, 151). In fully adjusted models, each 1000 steps /day was associated with lower CAC (p=0.024). Results were examined by sex and age subgroups (0.05). Similarly, significant inverse associations between MVPA minutes and CAC AS were found in women ( Suggested sex differences in the PA-CAC association in adults with initial glucose intolerance was found and should be investigated in other studies. Disclosure B. Rockette-wagner: None. E. Horton: None. M. A. Hoskin: None. U. N. Ibebuogu: None. M. Schlögl: None. R. B. Goldberg: None. D. Research group: None. A. Kriska: None. N. Younes: None. S. Edelstein: None. T. J. Orchard: None. M. Armstrong: None. A. L. Brown: Research Support; Self; Medtronic, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases. D. Dabelea: None. K. M. Gadde: Other Relationship; Self; AstraZeneca, Research Support; Self; BioKier, National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048489)

ImportanceHypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.ObjectiveTo study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool.DesignA cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training.SettingThree tertiary care hospitals in Rwanda.ParticipantsHealthcare professionals (n=223).Primary outcome(s) and measure(s)The COACH tool consists of 49 items with eight subscales: resources, community engagement, commitment to work, informal payment, leadership, work culture, monitoring services for action (5-point Likert Scale) and sources of knowledge (on a 0–1 scale). Four questions surveyed training on hypertension.ResultsResponders (n=223, 75% women; 56% aged 20–35 years) included nurses (n=142, 64%, midwives (n=42, 19%), primary care physicians (n=28, 13%) and physician specialists (n=11, 5%)). The subscales commitment to work, leadership, work culture and informal payment scored between 4.7 and 4.1 and the community engagement, monitoring services for action and organizational resources scored between 3.1 and 3.5. Sources of knowledge had a mean score of 0.6±0.3. While 73% reported having attended a didactic hypertension seminar in the past year, only 28% had received long-term training and 51% had ConclusionsThere is a need for increased and continuous training in Rwanda. Healthcare responders stated a commitment to work and reported supportive leadership, while acknowledging limited resources and no monitoring systems. The COACH tool provides contextual guidance to develop training strategies prior to the implementation of a sustainable hypertension care programme.

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as “proactive prevention.” This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a 2-by-2 matrix: high impact/high feasibility, high impact/ low feasibility, low impact/high feasibility, and low impact/low feasibility. We propose that high impact/high feasibility interventions are ready to be implemented (act), while high impact/low feasibility interventions require efforts to foster buy-in first. Low impact/high feasibility interventions need to be changed to improve their impact while low impact/low feasibility might be best re-designed in the context of limited resources. Using this framework, policy makers, public health experts, and other stakeholders can more effectively prioritize and leverage limited resources in an effort to slow or prevent the evolving global NCD crisis. Fil: Njuguna, Benson. Moi Teaching & Referral Hospital; Kenia Fil: Fletcher, Sara L.. State University of Oregon; Estados Unidos Fil: Akwanalo, Constantine. Moi Teaching & Referral Hospital; Kenia Fil: Asante, Kwaku Poku. Kintampo Health Research Centre; Ghana Fil: Baumann, Ana. Washington University in St. Louis; Estados Unidos Fil: Brown, Angela. Washington University in St. Louis; Estados Unidos Fil: Davila Roman, Victor G.. Washington University in St. Louis; Estados Unidos Fil: Dickhaus, Julia. New York University Grossman School of Medicine; Estados Unidos Fil: Fort, Meredith. Colorado School Of Public Health; Estados Unidos Fil: Iwelunmor, Juliet. Saint Louis University; Estados Unidos Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Mohan, Sailesh. Centre For Chronic Disease Control; India. Public Health Foundation Of India; India Fil: Mutabazi, Vincent. Regional Alliance For Sustainable Development; Ruanda Fil: Newsome, Brad. Center for Translation Research and Implementation Science; Estados Unidos Fil: Ogedegbe, Olugbenga. New York University Grossman School of Medicine; Estados Unidos Fil: Pastakia, Sonak D.. Purdue University College Of Pharmacy; Estados Unidos Fil: Peprah, Emmanuel K.. University of New York; Estados Unidos Fil: Plange Rhule, Jacob. Ghana College Of Physicians And Surgeons; Ghana Fil: Roth, Gregory. University of Washington; Estados Unidos Fil: Shrestha, Archana. Kathmandu University School Of Medical Sciences; Nepal Fil: Watkins, David A.. University of Washington; Estados Unidos Fil: Vedanthan, Rajesh. New York University Grossman School of Medicine; Estados Unidos

Background Hypertension (HTN) affects nearly 1 billion people globally and is a major cause of morbidity and mortality. In low- and middle-income countries (LMICs), HTN represents an unmet health care gap that can be addressed by strengthening national health care systems. The National Heart, Lung, and Blood Institute recently funded the T4 Translation Research Capacity Building Initiative in Low Income Countries (TREIN) program to build capacity in dissemination and implementation (D&I) research in HTN in LMICs. The Special Programme for Research and Training in Tropical Diseases (TDR) at the World Health Organization (WHO) recently developed a massive open online course (MOOC) to train in D&I. Herein, we report on the use of the TDR WHO MOOC in D&I for the TREIN program in Rwanda, assessing feasibility of the MOOC and D&I competencies after MOOC training. Methods Participants in one-group MOOC training completed pre- and post-training questionnaires to assess dissemination and implementation (D&I) competency outcomes and feasibility. D&I competencies were measured by use of a scale developed for a US-based training program, with the change in competency scores assessed by paired t test. Feasibility was measured by completion of homework and final project assignment and analyzed using descriptive statistics. Results Of the 92 trainees enrolled, 35 (38%) completed all MOOC components. D&I competency scores showed strong evidence of improvements from pre- to post-test. The full-scale average score improved by an average of 1.09 points, representing an effect size of 1.25 (CI 0.48-2.00); all four subscales also showed strong evidence of improvements. Trainees reported challenges to MOOC course completion that included technological issues (i.e., limited internet access) and competing demands (i.e., work, family). Conclusions In the context of LMIC training, the MOOC course was feasible and course completion showed improvement in D&I competency scores. While the program was designed with a focus on training for tropical diseases, there is potential for scalability to a wider audience of health care researchers, workers, administrators, and policymakers in LMIC interested in D&I research in non-communicable diseases.

Summary Background Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT02439749 . Findings From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding Medtronic.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and in low- and middle-income countries, and hypertension (HTN) is a major risk factor for CVD. Although effective evidence-based interventions for control of HTN in high-income countries exist, implementation of these in low- and middle-income countries has been challenging due to limited capacity and infrastructure for latephase translational research. In Rwanda, the 2015 STEPS NCD (STEPwise Approach to Surveillance of Noncommunicable Diseases) risk survey reported an overall prevalence of HTN of 15% (95% confidence interval [CI]: 13.8 to 16.3) for those ages 15 to 64 years; prevalence increased with increasing age to 39% (95% CI: 35.7 to 43.1) for those ages 55 to 64 years; CVD was the third most common cause of mortality (7%). Suboptimal infrastructure and capacity in Rwanda hinders research and community knowledge for HTN control.Objectives: To address the issue of suboptimal capacity to implement evidence-based interventions in HTN, this project was designed with the following objectives: 1) to develop a regional needs assessment of infrastructure for dissemination and implementation (D & I) strategies for HTN-CVD control; 2) to develop HTNCVD research capacity through creation of countrywide resources such as core research facilities and training in the fields of HTN-CVD, D & I, and biostatistics; and 3) to engage and train multiple stakeholders in D & I and HTN-CVD evidence-based interventions.Methods: A weeklong training program in HTN-CVD, biostatistics, and D & I was conducted in Rwanda in August 2018, and pre- and post-D & I training competency questionnaires were administered.Results: Questionnaire results show a statistically significant increase in D & I knowledge and skills as a result of training (full scale pre- to post-test scores: 2.12 ± 0.78 vs. 3.94 ± 0.42; p < 0.0001).Conclusions: Using principles of community engagement and train-the-trainer methods, we will continue to adapt guidelines and treatments for HTN-CVD developed in high-income countries to the context of Rwanda with the goal of establishing a sustainable platform to address the burden of disease from HTN-CVD.HighlightsImplementation research in LMIC has been challenging due to limited capacity.A training program was developed to support implementation research strategies in Rwanda.Implementation research training resulted in significant increases in knowledge and skills.

The SYMPLICITY HTN-3 trial, which randomized subjects to renal denervation (RDN) or sham control, was designed to evaluate the efficacy and safety of RDN for the treatment of resistant hypertension. Outcomes were previously reported. This retrospective analysis evaluated reasons for screen failure (SF) for randomization in the trial.SYMPLICITY HTN-3 enrolled subjects with office systolic blood pressure (SBP) ≥160 mmHg on stable and maximal doses of ≥3 antihypertensive medication classes. Blood pressure was measured during screening visit (SV) 1 and SV2 a minimum of 2 weeks later to ensure resistant hypertension and to exclude white-coat hypertension. We analyzed baseline characteristics and reasons for SF at each SV and changes in BP between SVs.Among 1,415 patients screened, 880 (62%) did not meet criteria for randomization. Compared with randomized patients, those in the SF cohort were more likely to be older (58.7 vs. 57.4 years, P=.029), current smokers (14.5% vs. 10.7%, P=.041), and prescribed fewer antihypertensive medications (4.7 vs. 5.1, P.001). The predominant reason for SF at SV2 was office SBP160 mmHg despite office SBP ≥160 mmHg at SV1.Screening patients with resistant hypertension on maximal doses of ≥3 antihypertensive drugs led to a high SF rate. Screen failures were most common at SV1 and were due to failing the office SBP entry criteria. Not meeting ambulatory SBP criteria at SV2 was a secondary reason for SF, often due to white-coat hypertension; thus, 24-hour ambulatory monitoring is important to validate resistant hypertension.

Highlights NCD represent a serious challenge globally, particularly in LMIC. Implementation research capacity building are critical to inform the prevention and control of NCD in LMIC. Sustainable evidence-based strategies can reduce mortality and prevent avoidable illness from NCD. Strategic change agents (i.e., key stakeholders, institutions, communities, health systems, patients, and families) should work collaboratively to make the necessary advancements to reducing the burden of NCD in LMIC.

Since the first International Society on Hypertension in Blacks consensus statement on the “Management of High Blood Pressure in African American” in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure–lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently 15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.

To investigate the correlations of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with echocardiographic measurements of left ventricular (LV) systolic and/or diastolic function.Plasma levels of NT-proBNP are increased in heart failure. The extent to which NT-proBNP levels increase in LV diastolic dysfunction has not been well characterized.Plasma NT-proBNP levels were measured in 191 consecutive, clinically stable, ambulatory patients. Echocardiography was used to determine LV systolic (LV ejection fraction [LVEF]) and diastolic function by mitral E wave to Doppler tissue early diastolic lateral annulus velocity ratio (E/Em). Patients with a history, physical findings, and/or echocardiographic evidence of cardiovascular disease (n = 148) were grouped as: (1) normal LV systolic function (LVEFor = 55%, n = 81); and (2) LV systolic dysfunction (LVEF55%, n = 67). They were compared to a group of healthy control subjects (n = 43). Multivariate regression analyses were used to determine significant correlations with plasma NT-proBNP levels.NT-proBNP levels correlated negatively with LVEF (P.001) and positively with E/Em (P = .001). Multivariate regression analysis demonstrated a significant correlation of NT-proBNP levels with LVEF (P.001) and E/Em (P = .03).In this clinically stable, ambulatory cohort of patients with cardiovascular disease and healthy control subjects, plasma NT-proBNP levels were significantly higher in those with LV systolic dysfunction and/or elevated filling pressures, independent of the effects of LV mass, renal function, and age. These results suggest that NT-proBNP levels may be a useful adjunct in the characterization of patients presenting with history and/or symptoms compatible with LV systolic and/or diastolic dysfunction.

A 2014 hypertension guideline raised goal systolic blood pressure (SBP) from 30% 0–1 health‐care visits per year) occurred in untreated black and white hypertensive patients without DM/CKD and BP ≥140/

Patient adherence to recommended therapy is a key factor in addressing the disparities in blood pressure control rates and hypertension-related complications between blacks and whites. Poor adherence to long-term therapy results in failure to achieve blood pressure targets, exacerbations of disease, increased hospitalizations and emergency department visits, adverse health outcomes, and increased preventable health care costs. Developing strategies to increase adherence, and ultimately improve blood pressure control rates and outcomes, requires an understanding of the complex interplay of the behavioral factors and belief systems that effect how patients interact with the health care system.

Background The pre-endoscopic Rockall Score (RS) and the Glasgow-Blatchford Scores (GBS) can help risk stratify patients with upper gastrointestinal bleed who are seen in the Emergency Department (ED). The RS and GBS have yet to be validated in a United States patient population for their ability to discriminate which ED patients with upper gastrointestinal bleed do not need endoscopic hemostasis. Objective We sought to determine whether patients who received a score of zero on either score (the lowest risk) in the ED still required upper endoscopic hemostasis during hospitalization. Methods Retrospective electronic medical record chart review was performed during a 3-year period (2007–2009) to identify patients with suspected upper gastrointestinal bleed by ED final diagnosis of gastrointestinal hemorrhage and related terms at a single urban academic ED. The RS and GBS were calculated from ED chart abstraction and the hospital records of admitted patients were queried for subsequent endoscopic hemostasis. Results Six hundred and ninety patients with gastrointestinal bleed were identified and 86% were admitted to the hospital. One hundred and twenty-two patients had an RS equal to zero; 67 (55%; 95% confidence interval [CI] 46–63%) of these patients were admitted to the hospital and 11 (16%; 95% CI 9–27%) received endoscopic hemostasis. Sixty-three patients had a GBS equal to zero; 15 (24%; 95% CI 15–36%) were admitted to the hospital and 2 (13%; 95% CI 4–38%) received endoscopic hemostasis. Conclusions Some patients who were identified as lowest risk by the GBS or RS still received endoscopic hemostasis during hospital admission. These clinical decision rules may be insufficiently sensitive to predict which patients do not require endoscopic hemostasis.

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss., Author Summary The study included 2,993 participants from the Diabetes Prevention Program, a randomized clinical trial of intensive lifestyle intervention, metformin treatment, and placebo control. We examined associations between 32 gene variants that have been reproducibly associated with dyslipidemia and concentrations of lipids and NMR lipoprotein particle sizes and numbers. We also examined whether genetic background influences a person's response to cardioprotective interventions on lipid levels. Our analysis, which focused on determining whether common genetic variants impact the effects of cardioprotective interventions on lipid and lipoprotein particle size, shows that in persons with a high genetic risk score the benefit of intensive lifestyle intervention on LDL and small LDL particle levels is substantially diminished; this information may be informative for the targeted prevention of dyslipidemia, as it suggests that genetics might help identify persons in whom lifestyle intervention is likely to be an effective treatment for elevated lipids and lipoproteins. The NMR subfraction analyses provide novel insight into the biology of dyslipidemia by illustrating how numerous genetic variants that have previously been associated with lipid levels also modulate NMR lipoprotein particle sizes and number. This information may be informative for the targeted prevention of cardiovascular disease.

The purpose of this report is to review available and emerging antihypertensive treatment options in light of current guidelines and evidence from large clinical trials. The published literature was reviewed for evidence regarding first-line options for antihypertensive agents, including thiazide-type diuretics, as monotherapy or as part of combination therapy. Current guidelines recommend using thiazide-type diuretics as first-line therapy alone or in combination with another agent. Other commonly used antihypertensive agents include calcium channel blockers, β-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and the direct renin inhibitor, aliskiren. These agents are associated with varying degrees of evidence that they may provide protection from cardiovascular or renal disease beyond that associated with blood pressure reduction. Thiazide diuretics are inexpensive and effective but may not be preferable to other classes of antihypertensives that reduce blood pressure to a similar extent with a better safety profile and superior reductions in cardiovascular event rates. However, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and direct renin inhibitors also show promise as initial monotherapy or as part of a combination therapy regimen. In patients requiring additional blood pressure reduction, add-on therapy with a diuretic could provide additional blood pressure-lowering efficacy.

Aim To characterize the extent to which metabolic syndrome criteria predict left ventricular (LV) structure and function. Methods and results Metabolic syndrome criteria were assessed in 607 adults with normal LV function. The cohort was grouped according to the number of criteria satisfied: (1) Absent (0 criteria, n = 110); (2) Pre-Metabolic Syndrome (1–2 criteria, n = 311); and (3) Metabolic Syndrome (≥3 criteria, n = 186). Echocardiography was used to assess LV structure (LV mass) and systolic (LVEF, Vs) and diastolic function, by pulse-wave Doppler (E/A ratio) and tissue Doppler imaging (Ve). LV volumes and LVEF were similar between groups. However, LV mass increased significantly and progressively (LVM/Ht2.7, in g/m2.7: 34.9 ± 6.7, 41.0 ± 9.5, 46.3 ± 11.0, P < 0.001); LV relaxation decreased progressively (Veglobal′, in cm/s: 13.5 ± 2.8, 12.1 ± 3.0, 10.5 ± 2.2, P < 0.001) from Absent to Pre-Metabolic Syndrome to Metabolic Syndrome groups, respectively. Multiple variable analyses showed that diastolic blood pressure, waist circumference, and triglyceride levels were independent predictors of Ve after adjustment for LV mass. Conclusion Patients with metabolic syndrome have LV diastolic dysfunction independent of LV mass. These functional abnormalities may partially explain the increased cardiovascular morbidity and mortality associated with metabolic syndrome.

Diastolic dysfunction, manifested by impaired left ventricular (LV) relaxation, is prevalent among individuals with metabolic disorders. The objective of this study was to evaluate the extent to which plasma triglyceride (TG) levels are related to LV diastolic function.A total of 424 subjects (age 49 +/- 12 years) had fasting plasma TG levels measured and underwent echocardiography for assessment of LV structure and function: LV ejection fraction and LV mass indexed to height (LVM/Ht(2.7)); transmitral inflow early diastolic peak velocity (E wave) and late diastolic peak velocity (A wave), and E wave to A wave ratio (E/A); deceleration time; and Doppler tissue imaging early diastolic myocardial velocity (EM), an index of LV relaxation.All subjects had normal LV ejection fraction, 48% had hypertension, 16% had increased LVM/Ht(2.7), 11% had type 2 diabetes mellitus, 37% were obese, and 27% had hypertriglyceridemia (TG150 mg/dL). Univariate analysis showed significant relationships between TG level and E/A, deceleration time, and Em (Por = .001 for all). After adjustment for potential confounders in multivariate models (eg, age, systolic blood pressure, and LVM/Ht(2.7)), TG levels remained predictive of E/A, deceleration time, and Em (Por = .05,.001, andor =.0001, respectively). Stepwise multivariate analysis showed that after age and body mass index, the TG level was the next most predictive variable of Em.Plasma TG levels show a strong relationship with impaired LV relaxation, an early marker of diastolic dysfunction in human beings. These findings support a hypothesis whereby elevated TG levels favor myocyte intracellular lipid accumulation, possibly leading to lipotoxic diastolic dysfunction.