Cardiovascular Risk Factors Are Associated With Future Cancer

BACKGROUND The extent to which co-occurrence of cardiovascular disease (CVD) and cancer is due to shared risk factors or other mechanisms is unknown. OBJECTIVES This study investigated the association of standard CVD risk factors, CVD biomarkers, pre-existing CVD, and ideal cardiovascular (CV) health metrics with the development of future cancer. METHODS This study prospectively followed Framingham Heart Study and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants free of cancer at baseline and ascertained histology-proven cancer. This study assessed the association of baseline CV risk factors, 10-year atherosclerotic (ASCVD) risk score, established CVD biomarkers, prevalent CVD, and the American Heart Association (AHA) Life's Simple 7 CV health score with incident cancer using multivariable Cox models. Analyses of interim CVD events with incident cancer used time-dependent covariates. RESULTS Among 20,305 participants (mean age 50 +/- 14 years; 54% women), 2,548 incident cancer cases occurred over a median follow-up of 15.0 years (quartile 1 to 3: 13.3 to 15.0 years). Traditional CVD risk factors, including age, sex, and smoking status, were independently associated with cancer (p < 0.001 for all). Estimated 10-year ASCVD risk was also associated with future cancer (hazard ratio [HR]: 1.16 per 5% increase in risk; 95% confidence interval [CI] 1.14 to 1.17; p < 0.001). The study found that natriuretic peptides (tertile 3 vs. tertite 1; HR: 1.40; 95% 0:1.03 to 1.91; p 0.035) were associated with incident cancer but not high-sensitivity troponin (p 0.47). Prevalent CVD and the development of interim CV events were not associated with higher risk of subsequent cancer. However, ideal CV health was associated with tower future cancer risk (HR: 0.95 per 1-point increase in the AHA health score; 95% CI: 0.92 to 0.99; p = 0.009). CONCLUSIONS CVD risk, as captured by traditional CVD risk factors, 10-year ASCVD risk score, and natriuretic peptide concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a lower risk of future cancer. These data suggest that the association between CVD and future cancer is attributable to shared risk factors. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Cardiovascular disease related circulating biomarkers and cancer incidence and mortality:is there an association?

Aims Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. Methods and results We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rat

Age dependent associations of risk factors with heart failure:pooled population based cohort study

OBJECTIVE: To assess age differences in risk factors for incident heart failure in the general population. DESIGN: Pooled population based cohort study. SETTING: Framingham Heart Study, Prevention of Renal and Vascular End-stage Disease Study, and Multi-Ethnic Study of Atherosclerosis. PARTICIPANTS: 24 675 participants without a history of heart failure stratified by age into young (<55 years; n=11 599), middle aged (55-64 years; n=5587), old (65-74 years; n=5190), and elderly (≥75 years; n=2299) individuals. MAIN OUTCOME MEASURE: Incident heart failure. RESULTS: Over a median follow-up of 12.7 years, 138/11 599 (1%), 293/5587 (5%), 538/5190 (10%), and 412/2299 (18%) of young, middle aged, old, and elderly participants, respectively, developed heart failure. In young participants, 32% (n=44) of heart failure cases were classified as heart failure with preserved ejection fraction compared with 43% (n=179) in elderly participants. Risk factors including hypertension, diabetes, current smoking history, and previous myocardial infarction conferred greater relative risk in younger compared with older participants (P for interaction <0.05 for all). For example, hypertension was associated with a threefold increase in risk of future heart failure in young participants (hazard ratio 3.02, 95% confidence interval 2.10 to 4.34; P<0.001) compared with a 1.4-fold risk in elderly participants (1.43, 1.13 to 1.81; P=0.003). The absolute risk for developing heart failure was lower in younger than in older participants with and without risk factors. Importantly, known risk factors explained a greater proportion of overall population attributable risk for heart failure in young participants (75% v 53% in elderly participants), with better model performance (C index 0.79 v 0.64). Similarly, the population attributable risks of obesity (21% v 13%), hypertension (35% v 23%), diabetes (14% v 7%), and current smoking (32% v 1%) were higher in young compared with elderly participants. CONCLUSIONS: Despite a lower incidence and absolute risk of heart failure among younger compared with older people, the stronger association and greater attributable risk of modifiable risk factors among young participants highlight the importance of preventive efforts across the adult life course

Association of Cardiometabolic Disease With Cancer in the Community

BACKGROUND: Obesity and cardiometabolic dysfunction have been associated with cancer risk and severity. Underlying mechanisms remain unclear. OBJECTIVES: The aim of this study was to examine associations of obesity and related cardiometabolic traits with incident cancer. METHODS: FHS (Framingham Heart Study) and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants without prevalent cancer were studied, examining associations of obesity, body mass index (BMI), waist circumference, visceral adipose tissue (VAT) and subcutaneous adipose tissue depots, and C-reactive protein (CRP) with future cancer in Cox models. RESULTS: Among 20,667 participants (mean age 50 years, 53% women), 2,619 cancer events were observed over a median follow-up duration of 15 years. Obesity was associated with increased risk for future gastrointestinal (HR: 1.30; 95% CI: 1.05-1.60), gynecologic (HR: 1.62; 95% CI: 1.08-2.45), and breast (HR: 1.32; 95% CI: 1.05-1.66) cancer and lower risk for lung cancer (HR: 0.62; 95% CI: 0.44-0.87). Similarly, waist circumference was associated with increased risk for overall, gastrointestinal, and gynecologic but not lung cancer. VAT but not subcutaneous adipose tissue was associated with risk for overall cancer (HR: 1.22; 95% CI: 1.05-1.43), lung cancer (HR: 1.92; 95% CI: 1.01-3.66), and melanoma (HR: 1.56; 95% CI: 1.02-2.38) independent of BMI. Last, higher CRP levels were associated with higher risk for overall, colorectal, and lung cancer (P < 0.05 for all). CONCLUSIONS: Obesity and abdominal adiposity are associated with future risk for specific cancers (eg, gastrointestinal, gynecologic). Although obesity was associated with lower risk for lung cancer, greater VAT and CRP were associated with higher lung cancer risk after adjusting for BMI

Galectin-3 inhibition with modified citrus pectin in hypertension

We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry.

BackgroundMen are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known.Study design and methodsWe examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression.ResultsInitial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, pConclusionsIn a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection

Galectin-3 inhibition with modified citrus pectin in hypertension

We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure Risk in Women

Objective: Greater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear. Methods: We examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n = 12,635 participants in the FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major cardiovascular disease, myocardia infarction and stroke. Results: Among n = 3931 FHS participants (mean age 48 ± 13 years), higher numbers of live births were associated with worse left ventricular fractional shortening (multivariable β -1.11 (0.31); P = 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics, including global circumferential strain and longitudinal and radial dyssynchrony (P < 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥ 5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19–3.12; P = 0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37–0.91; P = 0.02). Conclusions: Greater numbers of live births are associated with worse cardiac structure and function. There was no association with overall HF, but a higher number of live births was associated with greater risk for incident HFrEF

Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy

The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells. Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF