Cardiovascular Journal of Africa: Vol 29 No 5 (September/October 2018)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018

AFRICA

321

et al.

Endothelial disruptive proinflammatory effects of nicotine and

e-cigarette vapour exposures.

Am J Physiol Lung Cell Mol Physiol

2015;

309

(2): L175–L187.

43. Lee J, Luria A, Rhodes C, Raghu H, Lingampalli N, Sharpe O,

et al.

Nicotine drives neutrophil extracellular traps formation and acceler-

ates collagen-induced arthritis.

Rheumatology

2017;

(4): 644–653. doi:

10.1093/rheumatology/kew449.

44. Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B,

et al.

Chronic electronic cigarette exposure in mice induces features of

COPD in a nicotine-dependent manner.

Thorax

2016;

(12): 1119-1129.

doi: 10.1136/thoraxjnl-2015-208039.

45. Feldman C, Anderson R. Cigarette smoking and mechanisms of suscepti-

bility to infections of the respiratory tract and other organ systems.

J Infect

2013;

(3): 169–184.

46. Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a

proinflammatory mediator of atherosclerosis.

Arterioscler Thromb Vasc

Biol

2004;

(12): 2227–2236.

47. Schrottmaier WC, Kral JB, Zeitlinger M, Salzmann M, Jilma B, Assinger

Platelet activation at the onset of human endotoxemia is undetectable

in vivo. Platelets

2016;

(5): 479–483.

48. Stavropoulos-Kalinoglou A, Metsios GS, Panoulas VF, Douglas KM,

Nevill AM, Jamurtas AZ,

et al.

Cigarette smoking associates with body

weight and muscle mass of patients with rheumatoid arthritis: a cross-

sectional, observational study.

Arthritis Res Ther

2008;

(3): R59.

49. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P,

et al.

The effects of tumour necrosis factor inhibitors, methotrexate, non-

steroidal anti-inflammatory drugs and corticosteroids on cardiovascular

events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a system-

atic review and meta-analysis.

Ann Rheum Dis

2015;

(3): 480–489.

50. Shen J, Shang Q, Tam LS. Targeting inflammation in the prevention of

cardiovascular disease in patients with inflammatory arthritis.

Transl Res

2016;

167

(1): 138–151.

51. Ridker PM. How common is residual inflammatory risk?

Circ Res

2017;

120

: 617–619. Doi: 10.1161/CIRCRESAHA.116.310527.

52. McPherson JA, Barringhaus KG, Bishop GG, Sanders JM, Rieger JM,

Hesselbacher SE,

et al

. Adenosine A(2A) receptor stimulation reduces

inflammation and neointimal growth in a murine carotid ligation model.

Arterioscler Thromb Vasc Biol

2001;

(5): 791–796.

53. Bulgarelli A, Martins Dias AA, Caramelli B, Maranhão RC. Treatment

with methotrexate inhibits atherogenesis in cholesterol-fed rabbits.

Cardiovasc Pharmacol

2012;

(4): 308–314.

54. Ridker PM. Testing the inflammatory hypothesis of atherothrombosis:

scientific rationale for the cardiovascular inflammation reduction trial

(CIRT).

J Thromb Haemost

2009;

(suppl 1): 332–339.

55. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1

inhibition and

the prevention of recurrent cardiovascular events: rationale and design

of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study

(CANTOS).

Am Heart J

2011;

162

(4): 597–605.

Mortality outcomes of original ASCOT trial reported

In patients with hypertension, the long-term cardiovascular

and all-cause mortality effects of different blood pressure-

lowering regimens and lipid-lowering treatment are not well

documented, particularly in clinical trial settings. Professor

Peter Sever at the National Heart and Lung Institute,

Imperial College London writes in The Lancet that the

Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

Legacy Study reports mortality outcomes after 16 years of

follow up of the UK participants in the original ASCOT

trial.

ASCOT was a multicentre randomised trial with a 2 × 2

factorial design. UK-based patients with hypertension were

followed up for all-cause and cardiovascular mortality for

a median of 15.7 years (IQR 9.7–16.4 years). At baseline,

all patients enrolled into the blood pressure-lowering arm

(BPLA) of ASCOT were randomly assigned to receive

either amlodipine-based or atenolol-based blood pressure-

lowering treatment. Of these patients, those who had

total cholesterol of 6.5 mmol/l or lower and no previous

lipid-lowering treatment underwent further randomisation

to receive either atorvastatin or placebo as part of the

lipid-lowering arm (LLA) of ASCOT. The remaining

patients formed the non-LLA group. A team of two

physicians independently adjudicated all causes of death.

Of 8 580 UK-based patients in ASCOT, 3 282 (38.3%) died,

including 1 640 (38.4%) of 4 275 assigned to atenolol-based

treatment and 1 642 (38.1%) of 4 305 assigned to amlodipine-

based treatment; 1 768 of the 4 605 patients in the LLA died,

including 903 (39.5%) of 2 288 assigned placebo and 865

(37.3%) of 2317 assigned atorvastatin. Of all deaths, 1 210

(36.9%) were from cardiovascular-related causes.

Among patients in the BPLA, there was no overall

difference in all-cause mortality between treatments [adjusted

hazard ratio (HR) 0.90, 95% CI: 0.81–1.01,

= 0.0776],

although significantly fewer deaths from stroke (adjusted

HR 0.71, 95% CI: 0.53–0.97,

= 0.0305) occurred in the

amlodipine-based treatment group than in the atenolol-based

treatment group.

There was no interaction between treatment allocation in

the BPLA and in the LLA. However, in the 3 975 patients

in the non-LLA group, there were fewer cardiovascular

deaths (adjusted HR 0.79, 95% CI: 0.67–0.93,

= 0.0046)

among those assigned to amlodipine-based treatment

compared with atenolol-based treatment (

= 0.022 for

the test for interaction between the two blood pressure

treatments and allocation to LLA or not). In the LLA,

significantly fewer cardiovascular deaths (HR 0.85, 95%

CI: 0.72–0.99,

= 0.0395) occurred among patients

assigned to statin than among those assigned placebo.

Our findings show the long-term beneficial effects on

mortality of antihypertensive treatment with a calcium

channel blocker-based treatment regimen and lipid-lowering

with a statin: patients on amlodipine-based treatment had

fewer stroke deaths and patients on atorvastatin had fewer

cardiovascular deaths more than 10 years after trial closure.

Overall, the ASCOT Legacy study supports the notion that

interventions for blood pressure and cholesterol are associated

with long-term benefits on cardiovascular outcomes.

Source:

Medical Brief 2018