An intensive phenotyping study to enable the future examination of genetic influences on hypertension-associated cardiovascular disease

Stanton, Alice; Fitzgerald, D; Hughes, Alun D.; Mayet, Jamil; O’Brien, Eoin; Nr, Poulter; Sever, PS; Shields, Denis C.; Thom, Simon; Trial, Anglo-Scandinavian Cardiac Outcomes

doi:10.1038/sj.jhh.1001089

Cited by 12 publications

(9 citation statements)

References 52 publications

(34 reference statements)

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“…Similarly, change in LA volume did not correlate with the change in E/e′ (r=−0.08; P=0. 17). Transmitral E/A ratio, E/e′, and e′/a′ were correlated at both time points as were the changes in these 3 variables between the 2 phases.…”

Section: Diastolic Function and La Sizementioning

confidence: 86%

“…17 In brief, ASCOT was a randomized clinical trial of BP-lowering therapy in 19 257 men and women aged 40 to 79 years with hypertension. Hypertension was defined as either untreated (systolic BP ≥160 mm Hg and diastolic BP ≥100 mm Hg at screening and randomization) or inadequately treated hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg at randomization).…”

Section: Patientsmentioning

confidence: 99%

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Long-Term Antihypertensive Treatment Fails to Improve E/e′ Despite Regression of Left Ventricular Mass

et al. 2014

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Abstract-Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the shortterm, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine±perindopril-based or an atenolol±bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (≈1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5-116.8; atenolol: 122.9-117.5; P<0.001 for both). Conversely, tissue Doppler diastolic indices did not change in the amlodipine±perindopril-based regimen (E/e′, 7.5-7.6 cm/s; P=not significant), but deteriorated in the atenolol±bendroflumethiazide-based regimen (E/e′, 8.0-8.5 cm/s; P<0.01). Despite regression of left ventricular hypertrophy, there was no associated improvement in diastolic function. In fact, long-term treatment with atenolol±bendroflumethiazide resulted in a progressive deterioration in E/e′. This may be a factor contributing to the previously described worse clinical outcome in patients treated with atenolol± Methods PatientsThe population, methods, and response rate for the ASCOT study are described in detail elsewhere. 17 In brief, ASCOT was a randomized clinical trial of BP-lowering therapy in 19 257 men and women aged 40 to 79 years with hypertension. Hypertension was defined as either untreated (systolic BP ≥160 mm Hg and diastolic BP ≥100 mm Hg at screening and randomization) or inadequately treated hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg at randomization). As well as hypertension the patients required ≥3 prespecified cardiovascular risk factors from previously identified LVH on echocardiography or electrocardiography, other specified electrocardiography abnormalities, type 2 diabetes mellitus, peripheral vascular disease, previous transient ischemic attacks or stroke, male sex, age ≥55 years, microalbuminuria/proteinuria, smoking, plasma total cholesterol/high-density lipoprotein ratio ≥6, and family history of ischemic heart disease in a first-degree relative (males aged <55 years, females aged <60 years). Patients with known ischemic heart disease or heart failure were excluded. The patients were then randomized to either atenolol±bendroflumethiazide-K (atenolol±bendroflumethiazide-based regimen) or amlodipine±perindopril (amlodipine±p...

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Section: Diastolic Function and La Sizementioning

confidence: 86%

Section: Patientsmentioning

confidence: 99%

Long-Term Antihypertensive Treatment Fails to Improve E/e′ Despite Regression of Left Ventricular Mass

et al. 2014

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“…ASCOT is a double-blind randomised 2x2 factorial study of blood-pressure-lowering and lipid-lowering treatment (16–18). A total of 14,412 patients (aged 40-79 years) were randomized between 1998 and 2000 using a computer-generated optimum allocation mechanism blinded for any person involved in the undertaking of the study.…”

Section: Methodsmentioning

confidence: 99%

Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes

et al. 2016

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MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-α-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids. Proteomics analysis of livers from antagomiR-122–treated mice revealed novel regulators of hepatic lipid metabolism that are responsive to miR-122 inhibition. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT, n = 155), 12-month atorvastatin reduced circulating miR-122. A similar response to atorvastatin was observed in mice and cultured murine hepatocytes. Over up to 15 years of follow-up in the Bruneck Study, multivariable adjusted risk ratios per one-SD higher log miR-122 were 1.60 (95% CI 1.30–1.96; P < 0.001) for metabolic syndrome and 1.37 (1.03–1.82; P = 0.021) for type 2 diabetes. In conclusion, circulating miR-122 is strongly associated with the risk of developing metabolic syndrome and type 2 diabetes in the general population.

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“…The population, methods, and response rate for the ASCOT study are described in detail elsewhere (15). In brief, the ASCOT study was a clinical trial of blood pressure (BP)-lowering regimens in 19,342 men and women, age 40 to 79 years, with hypertension.…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Antihypertensive Treatment on Left Ventricular Diastolic Function

Tapp

Sharp

Stanton

et al. 2010

Journal of the American College of Cardiology

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An intensive phenotyping study to enable the future examination of genetic influences on hypertension-associated cardiovascular disease

Cited by 12 publications

References 52 publications

Long-Term Antihypertensive Treatment Fails to Improve E/e′ Despite Regression of Left Ventricular Mass

Long-Term Antihypertensive Treatment Fails to Improve E/e′ Despite Regression of Left Ventricular Mass

Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes

Differential Effects of Antihypertensive Treatment on Left Ventricular Diastolic Function

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