Complex relationship of obesity and obesity paradox in heart failure – higher risk of developing heart failure and better outcomes in established heart failure

Figures & data

Table 1. Selected studies on obesity and obesity paradox on heart failure and its outcomes.

Study	Study type	Sample size	Mean age (years)	Follow-up (years)	Type of heart failure	Outcome (CI)-HF risk or incidence/mortality
I. Selected studies on heart failure risk or heart failure incidence
Voulgari et al. (2011) (26)	Prospective cohort study	550	Without HF 55 ± 9, With HF 59 ± 8	6 years	Both HFpEF and HFrEF	HF risk: Increased with normal weight with METS HR 2.33, 95% CI 1.25–4.36 Decreased in overweight without METS HR 1.12, 95% CI 0.35–1.33 Decreased in obese without METS HR 0.41, 95% CI 0.10–1.31
Morkedal et al. (2014) (27)	Population based prospective cohort study	61,299	BMI <25 Healthy 44.3 ± 16.4, Unhealthy 60.1 ± 16.9 BMI 25–29.9 Healthy 48.0 ± 15.6, Unhealthy 56.7± 16.0 BMI >30 Healthy 50.6 ± 16.5, Unhealthy 55.2 ± 15.9	12 years	Not specified	HF risk: Metabolically healthy obese 1.7 (95% CI 1.3–2.9) Metabolically unhealthy obese 1.7 (95% CI 1.4–2.2)
Aune et al. (2016) (28)	Meta-analysis	6,47,388	Not mentioned in the study, but varying age groups	5–20 years	Different types of HF	HF Incidence  - RR for a 5-unit increase in BMI 1.41 (95% CI 1.34–1.47)- RR for a 10 cm increase in waist circumference, 1.29 (95% CI 1.21–1.37)- RR for a 0.1 increment in waist–hip ratio, 1.28, 95% CI 1.12–1.47) HF mortality RR for a 5-unit increase in BMI 1.26 (95% CI 0.85–1.87)
II. Selected studies on heart failure mortality in established heart failure
Orepoulos et al. (2008) (88)	Meta-analysis	28,209	Normal – 69 years Overweight – 67 years Obese – 62 years Underweight – 68 years	2.8 years	Different types of HF	Overweight was associated with lower all-cause mortality (RR 0.84, 95% CI 0.79–0.90) and CV mortality (RR 0.81, 95% CI 0.72–0.92). Obesity was associated with lower all-cause mortality (RR 0.67, 95% CI 0.62–0.73) and CV mortality (RR 0.60, 95% CI 0.53–0.69)
Sharma et al. (2015) (28)	Meta-analysis	22,807	BMI <20–70.6, BMI 20–24.9–67.7, BMI 25–29.9–66.2, BMI 30–34.9–63.1, BMI >35–64.3	2.85 years	Different types of HF	Low BMI (<20 kg/m^2) Increase in total mortality – RR 1.27, 95% CI 1.17–1.37 and CV mortality – RR 1.20, 95% CI 1.01–1.43 Overweight Decreased risk for CV mortality, RR 0.79, 95% CI 0.70–0.90
Lavie et al. (2013) (29)	Prospective cohort	2066	Low FIT BMI 18.5–24.9, 60 ± 14 BMI 25.0–29.9, 59 ± 13, BMI >30, 55 ± 13. High FIT BMI 18.5–24.9, 55 ± 17 BMI 25.0–29.9, 57 ± 14, BMI >30, 54 ± 13	5 years	Systolic HF	Obesity paradox persists in the low fit group (log rank 11.7, p = 0.003), but not in the high fit group (log rank 1.72, p = 0.42)
Khalid et al. (2014) (ARIC study) (30)	Prospective cohort study	1487	67 ± 6	10 years	Different types of heart failure	Pre-morbid BMI was associated with improved survival after HF in over weight (HR 0.77; 95% CI 0.62–0.96) and obesity (HR 0.75; 95% CI 0.61–0.91) when compared with normal BMI
Clark et al. (2011) (31)	Prospective cohort	344	53.3 ± 13.1	2 years	Systolic HF	Normal waist circumference when compared with high waist circumference was associated with higher all-cause mortality (RR 2.76, 95% CI 1.34–5.71)
Clark et al. (2015) (32)	Prospective cohort	1675	52.2 ± 11.6	2 years	Systolic HF	In low PKVO2, obese patients had decreased risk of death when compared with normal BMI (HR 0.64, 95% CI 9.44–0.91, p = 0.01)
Kamiya et al. (2016) (33)	Prospective cohort	570	67.4 ± 14.0	1.5 years	Different types of heart failure	BMI (HR 0.68, 95% CI 0.49–0.93, p = 0.016), waist circumference (HR 0.76, 95% CI 0.58–0.99, p = 0.044) and mid upper arm circumference (HR 0.52, 95% CI 0.39–0.72, p < 0.001) were all inversely associated with all-cause mortality

Figure 1. Mechanisms contributing to HF and mortality in obesity and obesity paradox.

Table 2. Traditional and new markers of obesity.

Traditional markers	New markers
Advantages: simple to assess, provide a snap shot of different measurements. Limitations: does not differentiate between the different components of body weight like muscle mass, fat, water, and skeletal weight.	Advantages: use special formulas, devices, or equipment. Help to determine the lean to fat ratio of the body weight. Some measure like visceral adiposity index could be an indicator of early metabolic risk.
1. Body weight	1. Body fat% calculation
2. BMI	2. Visceral adiposity index
3. Waist circumference	3. Body composition analysis
4. Waist–hip ratio	4. Sarcopenic status assessment

Table 3. Types (phenotypes) of obesity.

1. Obesity based on BMI	Obesity defined based on BMI≥ 30 kg/m^2.
2. Sarcopenic obesity	Obesity based on muscle mass index and muscle strength.
3. Metabolically normal/abnormal obesity	Obesity with or without abnormal metabolic profile/metabolic syndrome, with or lack of metabolic abnormalities like dyslipidemia, diabetes mellitus and hypertension.
4. Obesity with high or low cardiorespiratory fitness	Obesity with high or low habitual physical activity.
5. Obesity with malnutrition	Obesity associated with deficiencies of micronutrients or markers of malnutrition.

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