March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular riskThe Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)

RESULTS The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin–ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan–Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin–ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.) abstr act

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1410489

Ezetimibe added to statin therapy after acute coronary syndromes

https://air.unimi.it/bitstream/2434/689390/2/main.pdf

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

Background Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain. Methods After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol–lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization). Results During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin–laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin–laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin–laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; Pandlt;0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; Pandlt;0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; Pandlt;0.001), musculoskeletal system (absolute excess, 0.7 percentage points; Pandlt;0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; Pandlt;0.001) and bleeding (absolute excess, 0.7 percentage points; Pandlt;0.001). Conclusions Among participants with atherosclerotic vascular disease, the addition of extended-release niacin–laropiprant to statin-based LDL cholesterol–lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.)

/pdf/effects-of-extended-release-niacin-with-laropiprant-in-high-37tig660zb.pdf

Effects of extended-release niacin with laropiprant in high-risk patients.

We examined associations of plasma concentrations of 25(OH)D and cause-specific mortality in a prospective study of older men living in the UK and included findings in meta-analyses of similar studies identified by a systematic search reporting on vascular and all-cause mortality. In a 13-year follow-up of 5409 men (mean baseline age 77 years), 1358 died from vascular and 1857 from non-vascular causes. Median season-adjusted baseline 25(OH)D concentration was 56 (interquartile range: 45-67) nmol/L. After adjustment for age and seasonality, higher concentrations of 25(OH)D were inversely and approximately linearly (log-log scale) associated with vascular and non-vascular mortality throughout the range 40-90 nmol/L. After additional adjustment for prior disease and cardiovascular risk factors, a doubling in 25(OH)D concentration was associated with 20% (95% confidence interval (CI): 9-30%) lower vascular and 23% (95% CI: 14-31%) lower non-vascular mortality. In meta-analyses of prospective studies, individuals in the top vs. bottom quarter of 25(OH)D concentrations had 21% (95% CI: 13-28%) lower vascular and 28% (95% CI: 24-32%) lower all-cause mortality.

Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths.

Summary
This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.

/pdf/optimum-dose-of-vitamin-d-for-disease-prevention-in-older-1xyuewhmnh.pdf

Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care.

Hypertension is a growing worldwide problem associated with an increased risk of cardiovascular morbidity and mortality. However, the rates of prevalence of hypertension are higher in some populations than others. Although ethnic and genetic factors have been implied in the past to explain this, the environmental influence and psychosocial factors may play a more important role than is widely accepted. Examining the non-genetic influences in future hypertension research may be necessary in order to clearly define the local blood pressure demographics and the global hypertensive disease burden.

/pdf/blood-pressure-demographics-nature-or-nurture-genes-or-23unatrxef.pdf

Blood pressure demographics: nature or nurture ... ... genes or environment?

https://www.internationaljournalofcardiology.com/article/S0167-5273(06)00286-5/pdf

Joseph Tomson

Papers

Effects of extended-release niacin with laropiprant in high-risk patients.

Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths.

Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care.

Blood pressure demographics: nature or nurture ... ... genes or environment?

Effects of omega-3 polyunsaturated fatty acids on metabolically active hormones in patients post-myocardial infarction