Long-term outcomes from the UK Biobank on the impact of coffee on cardiovascular disease, arrhythmias, and mortality: Does the future hold coffee prescriptions?

Abstract

Introduction: Coffee is a popular beverage and the most used psychostimulant worldwide. Habitual coffee consumption has been linked to a growing list of health benefits; however, coffee consumption has been a source of longstanding debate. Recent observational studies have challenged the misconception of caffeine and reported the safety and beneficial effects of coffee intake on a range of cardiovascular (CV) conditions, including coronary artery disease, arrhythmias, heart failure, and stroke, leading to a decreased risk of CVD, all-cause and CVD mortality, and being associated with favorable CV outcomes. However, the mechanisms underlying the protective effects of caffeine remain speculative, and there is a lack of dedicated studies aimed at addressing the impact of different coffee subtypes on clinical outcomes such as CVD, arrhythmia, and mortality. Study and Results: The study included 449,563 UK Biobank participants, free of cardiovascular problems at enrollment (median age 58 years; 55.3% females). The median follow-up time was 12.5 years. Drinking 4 to 5 cups/day of ground (HR 0.83; 95% CI [0.76-0.91]; P < .0001) or 2 to 3 cups/day of instant (HR, 0.88; 95% CI [0.85-0.92]; P < .0001) coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia, including AF. Habitual coffee intake of up to 5 cups/day was associated with significant reductions in the risk of incident CVD, CHD (HR 0.89, CI [0.86-0.91], P < 0.0001), CCF (HR 0.83, CI [0.79-0.87], P < 0.0001), and ischemic stroke (HR 0.84, CI [0.78-0.90], P < 0.0001). Coffee consumption led to significant reductions in all-cause mortality (HR 0.86, CI [0.83-0.89], P < 0.0001) and CV mortality (HR 0.82, CI [0.74-0.90], P < 0.0001). Consumption of ground coffee at all levels significantly reduced the risk of all-cause and CV mortality. There was no significant difference in the incidence of CVD among all intake categories or across all coffee subtypes.

Lessons learned: The results from the UK Biobank indicate that mild-to-moderate consumption of all types of coffee is linked to improved CV outcomes and a lower risk of cardiovascular disease and death, with caffeinated coffee significantly reducing the risk of arrhythmias, including AF. Daily coffee intake should not be discouraged by physicians, even in the presence of a newly developed cardiovascular disease. Whether coffee will be prescribed in the future to prevent CVD and improve cardiovascular health depends on further evaluation of the physiological mechanisms and elucidation of the specific protective effects of coffee consumption.

Figure 1.. The main compounds of coffee: caffeine, chlorogenic acids, and other phenolics, and their anti-inflammatory and antioxidant effects.

Figure 2.. Summary of all major effects of coffee constituents on glucose and lipid metabolism, blood pressure, and waist circumference.

Coffee contains many biologically active substances, including caffeine, chlorogenic acids (CGAs), and diterpenes as cafestol and kahweol, which exert different metabolic effects. Regarding glucose metabolism, caffeine effect insulin release, predominantly, increasing b-cells secretion and reducing their damage. At the same time, CGAs have different effects on glucose absorption and insulin sensitivity by inhibiting salivary and pancreatic a-amylase, a-1,4-glucosidase, and glucose-6-phosphatase secretion of incretins and by inducing the translocation of GLUT-4, responsible for glucose uptake by peripheral tissues. The acute hypertensive effect of coffee is mainly mediated by caffeine, stimulating sympathetic activation with vasoconstriction, increased aortic stiffness, and cardiac automatism, while in the long-term exposure, CGAs reduce oxidative stress by improving endothelial function and the bioavailability of nitric oxide, resulting in a reduction in blood pressure following chronic coffee intake. Regarding the effect of coffee consumption on waist circumference, caffeine stimulates the sympathetic nervous system increasing resting metabolic rate and energy expenditure, and promotes cellular thermogenesis and lipolysis. Simultaneously, CGAs act to suppress the accumulation of hepatic triglycerides via down-regulation of genes associated with adipogenesis and up-regulation of genes involved in fatty acid oxidation. Finally, about lipid metabolism, caffeine and CGAs have been shown to suppress the activity of enzymes for lipid synthesis, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase, and to increase fatty acid b-oxidation by stimulating carnitine palmitoyltransferase and by activating PPAR-a in the liver and adipose tissues. Meanwhile, CGAs alone can control lipogenesis by down-regulating sterol regulatory element-binding protein (SREBP)-1C. Cafestol and kahweol have been shown to increase blood cholesterol levels by inhibiting bile acid synthesis acting on farnesoid X receptors. Therefore, habitual coffee consumption has been associated with a reduction in the risk of diabetes, hypertension, abdominal obesity, a reduction in triglycerides levels, and increased HDL cholesterol levels, resulting in a reduction in the risk of metabolic syndrome overall.

Figure 3.. Physiological effects of habitual caffeine consumption on the cardiovascular system. Adapted from.

Figure 4.. The impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality: long-term outcomes from the UK Biobank.