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Calcific Aortic Stenosis: A Review

Author/s: 
Catherine M Otto, David E Newby, Graham S Hillis

Importance: Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually.

Observations: Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher.

Conclusions: Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.

Keywords 
Valvular Heart Disease Cardiology aortic valve surgery Calcific Aortic Stenosis aortic stenosis

Transient ischemic attack and minor stroke: diagnosis, risk stratification and management

Author/s: 
Perry, J. J., Yadav, K., Syed, S., Shamy, M.

Patients with suspected cerebral ischemia should be urgently assessed to distinguish between transient ischemic attack (TIA), minor stroke or mimics such as migraine, seizure, vertigo or syncope.

The Canadian TIA Score can be used to determine risk for early subsequent stroke in patients with a suspected TIA or minor stroke.

All patients with TIA or minor stroke should undergo urgent electrocardiography and computed tomography of the head.

Clinicians should order early vascular imaging for patients at moderate or high risk of subsequent stroke; urgent revascularization should be considered if there is more than 50% arterial stenosis congruent with symptom presentation.

Clinicians should prescribe dual antiplatelet drugs for high-risk patients, single antiplatelet agents for low-risk patients or direct oral anticoagulants for patients with atrial fibrillation.

All patients with TIA or minor stroke should be counselled about modifiable lifestyle factors (including smoking cessation), be treated with statins and take steps toward optimizing blood pressure, including treatment with antihypertensive drugs, if necessary.

Keywords 
atrial fibrillation Brain Ischemia Cerebral Infarction Migraine Disorders electrocardiography

Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis

Garlic supplements have shown effectiveness in reducing blood pressure in hypertensive patients, similarly to first-line standard anti-hypertensive medications. Kyolic garlic has also shown promise in improving cardiovascular health by reducing arterial stiffness, elevated cholesterol levels and blood ‘stickiness’. In addition, the prebiotic properties in garlic increase gut microbial richness and diversity. This article systematically reviews previously published trials investigating the effects of garlic on blood pressure, and provides an updated meta-analysis of hypertensive participants. In addition, we summarise the findings of recent clinical trials investigating the effects of Kyolic aged garlic extract on arterial stiffness, and gut microbiota in hypertensive subjects. We searched online electronic databases, including PubMed and Google Scholar for randomised controlled trials (RCTs) published between 1955 and December, 2018 examining the effects of garlic on high blood pressure. The meta-analysis of 12 trials and 553 hypertensive participants confirmed that garlic supplements lower systolic blood pressure (SBP) by an average of 8.3±1.9 mmHg and diastolic blood pressure (DBP, n=8 trials, n=374 subjects) by 5.5±1.9 mmHg, similarly to standard anti-hypertensive medications. This reduction in blood pressure was associated with a 16–40% reduction in the risk of suffering from cardiovascular events. Additionally, this review summarises new evidence for the vitamin B12 status playing an important role in the responsiveness of blood pressure to garlic. Furthermore, Kyolic aged garlic extract significantly lowered central blood pressure, pulse pressure, pulse wave velocity and arterial stiffness, and improved the gut microbiota, evidenced by higher microbial richness and diversity, with a marked increase in the numbers of Lactobacillus and Clostridia species found following 3 months of supplementation. Thus, Kyolic aged garlic extract is considered to be highly tolerable with a high safety profile either as a stand-alone or adjunctive anti-hypertensive treatment, with multiple benefits for cardiovascular health.

Keywords 
aged garlic extract blood pressure hyptertension arterial stiffness gut microbiome

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

Author/s: 
Mackenzie, I. S., Rogers, A., Poulter, N. R., Williams, B., Brown, M. J., Webb, D. J., Ford, I., Rorie, D. A., Guthrie, G., Grieve, J. W. K., Pigazzani, F., Rothwell, P. M., Young, R., McConnachie, A., Struthers, A. D., Lang, C. C., MacDonald, T. M.

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the evening (2000-0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete.

Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9-5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62-0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65-0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83-1·10]; p=0·53). No safety concerns were identified.

Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.

Funding: British Heart Foundation.

Keywords 
Intention to Treat Analysis Antihypertensive Agents Cardiovascular Diseases Surveys and Questionnaires United Kingdom

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial

Author/s: 
Lean, Michael E.J., Leslie, Wilma S., Barnes, Alison C., Brosnahan, Naomi, Thom, George, McCombie, Louise, Peters, Carl, Zhyzhneuskaya, Sviatlana, Al-Mrabeh, Ahmad, Hollingsworth, Kieren G., Rodrigues, Angela M., Rehackova, Lucia, Adamson, Ashley J., Sniehotta, Falko F., Mathers, John C., Ross, Hazel M., McIlvenna, Yvonne, Stefanetti, Renae, Trenell, Michael, Welsh, Paul, Kean, Sharon, Ford, Ian, McConnachie, Alex, Sattar, Naveed, Taylor, Roy

BACKGROUND:

Type 2 diabetes is a chronic disorder that requires lifelong treatment. We aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes.

METHODS:

We did this open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in Scotland and the Tyneside region of England. Practices were randomly assigned (1:1), via a computer-generated list, to provide either a weight management programme (intervention) or best-practice care by guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700). Participants, carers, and research assistants who collected outcome data were aware of group allocation; however, allocation was concealed from the study statistician. We recruited individuals aged 20-65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27-45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825-853 kcal/day formula diet for 3-5 months), stepped food reintroduction (2-8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months. These outcomes were analysed hierarchically. This trial is registered with the ISRCTN registry, number 03267836.

FINDINGS:

Between July 25, 2014, and Aug 5, 2017, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8-49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0-5 kg weight loss, 19 (34%) of 56 participants with 5-10 kg loss, 16 (57%) of 28 participants with 10-15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by 10·0 kg (SD 8·0) in the intervention group and 1·0 kg (3·7) in the control group (adjusted difference -8·8 kg, 95% CI -10·3 to -7·3; p<0·0001). Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points (SD 21·3) in the intervention group, and decreased by 2·9 points (15·5) in the control group (adjusted difference 6·4 points, 95% CI 2·5-10·3; p=0·0012). Nine serious adverse events were reported by seven (4%) of 157 participants in the intervention group and two were reported by two (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. No serious adverse events led to withdrawal from the study.

INTERPRETATION:

Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care.

Keywords 
diet diabetes type 2 diabetes

Yoga as Antihypertensive Lifestyle Therapy: A Systematic Review and Meta-analysis

Author/s: 
Wu, Yin, Johnson, Blair T., Acabchuk, Rebecca L., Chen, Shiqi, Lewis, Holly K., Livingston, Jill, Park, Crystal L., Pescatello, Linda S.

OBJECTIVE:

To investigate the efficacy of yoga as antihypertensive lifestyle therapy and identify moderators that account for variability in the blood pressure (BP) response to yoga.

METHODS:

We systematically searched 6 electronic databases from inception through June 4, 2018, for articles published in English language journals on trials of yoga interventions that involved adult participants, reported preintervention and postintervention BP, and had a nonexercise/nondiet control group. Our search yielded 49 qualifying controlled trials (56 interventions). We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analysis following random-effects assumptions, and (3) generated additive models that represented the largest possible clinically relevant BP reductions.

RESULTS:

On average, the 3517 trial participants were middle-aged (49.2±19.5 years), overweight (27.9±3.6 kg/m2) adults with high BP (systolic BP, 129.3±13.3 mm Hg; diastolic BP, 80.7±8.4 mm Hg). Yoga was practiced 4.8±3.4 sessions per week for 59.2±25.0 minutes per session for 13.2±7.5 weeks. On average, yoga elicited moderate reductions in systolic BP (weighted mean effect size, -0.47; 95% CI, -0.62-0.32, -5.0 mm Hg) and diastolic BP (weighted mean effect size, -0.47; 95% CI, -0.61 to -0.32; -3.9 mm Hg) compared with controls (P<.001 for both systolic BP and diastolic BP). Controlling for publication bias and methodological study quality, when yoga was practiced 3 sessions per week among samples with hypertension, yoga interventions that included breathing techniques and meditation/mental relaxation elicited BP reductions of 11/6 mm Hg compared with those that did not (ie, 6/3 mm Hg).

CONCLUSION:

Our results indicate that yoga is a viable antihypertensive lifestyle therapy that produces the greatest BP benefits when breathing techniques and meditation/mental relaxation are included.

Keywords 
yoga hypertension blood pressure mindfulness meditation
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