Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data.

BACKGROUND: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population. METHODS: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5-25.0 kg/m2; 25.0-30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival. RESULTS: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity. CONCLUSIONS: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

Hypertensive Exposure Markers by MRI in Relation to Cerebral Small Vessel Disease and Cognitive Impairment.

OBJECTIVES: This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health. BACKGROUND: Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by pulse wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio. METHODS: A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 ± 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly. RESULTS: Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment. CONCLUSIONS: The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical blood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD.

Cerebral cortical microinfarcts: A novel MRI marker of vascular brain injury in patients with heart failure.

BACKGROUND: Patients with heart failure (HF) are at risk for vascular brain injury. Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of vascular brain injury. This study aims to determine the occurrence of CMIs in patient with HF and their clinical correlates, including haemodynamic status. METHODS: From the Heart-Brain Study, a multicenter prospective cohort study, 154 patients with clinically stable HF without concurrent atrial fibrillation (mean age 69.5 ± 10.1, 32% female) and 124 reference participants without HF (mean age 65.6 ± 7.4, 47% females) were evaluated for CMIs on 3 T MRI. CMI presence in HF was tested for associations with vascular risk profile, cardiac function and history, MRI markers of vascular brain injury and cognitive profile. RESULTS: CMI occurrence was higher in patient with HF (17%) than reference participants (7%); after correction for age and sex OR 2.5 [95% CI 1.1-6.0] p = .032; after additional correction for vascular risk factors OR 2.7 [1.0-7.1] p = .052. In patients with HF, CMI presence was associated with office hypertension (OR 2.7 [1.2-6.5] p = .021) and a lower cardiac index (B = -0.29 [-0.55--0.04] p = .023 independent of vascular risk factors), but not with cause or duration of HF. Presence of CMIs was not associated with cognitive performance in patients with HF. CONCLUSIONS: CMIs are a common occurrence in patients with HF and related to an adverse vascular risk factor profile and severity of cardiac dysfunction. CMIs thus represent a novel marker of vascular brain injury in these patients.