Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60–65 versus <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50–2.01]), hypertension (8 studies; 2.87 [2.09–3.93]), diabetes (9 studies; 3.20 [2.26–4.53]), and CVD (10 studies; 4.97 [3.76–6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19.

Background Individuals on dialysis have a high risk of infection, but risk of infection in earlier stages of chronic kidney disease (CKD) has not been comprehensively described. Study Design Observational cohort study. Setting & Participants 9,697 participants (aged 53–75 years) in the Atherosclerosis Risk in Communities (ARIC) Study. The participants were followed up from 1996–1998 through 2011. Predictors Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) Outcomes Risk of hospitalization with infection, and death during or within 30-days of hospitalization with infection. Results During follow-up (median, 13.6 years), there were 2,701 incident hospitalizations with infection (incidence rate, 23.6 per 1,000 person-years) and 523 infection-related deaths. In multivariable analysis, the HRs of incident hospitalization with infection as compared to eGFR ≥90 ml/min/1.73 m2 were 2.55 (95% CI, 1.43–4.55), 1.48 (95% CI, 1.28–1.71), and 1.07 (95% CI, 0.98–1.16) for eGFR 15–29, 30–59, and 60–89 ml/min/1.73 m2, respectively. Corresponding HRs were 3.76 (95% CI, 1.48–9.58), 1.62 (95% CI, 1.20–2.19), and 0.99 (95% CI, 0.80–1.21) for infection-related death. Compared to ACR <10 mg/g, the HRs of incident hospitalization with infection were 2.30 (95% CI, 1.81–2.91), 1.56 (95% CI, 1.36–1.78), and 1.34 (95% CI, 1.20–1.50) for ACR ≥300, 30–299, and 10–29 mg/g, respectively. Corresponding HRs were 3.44 (95% CI, 2.28–5.19), 1.57 (95% CI, 1.18–2.09), and 1.39 (95% CI, 1.09–1.78) for infection-related death. Results were consistent when separately assessing risk for pneumonia, kidney and urinary tract infections, blood stream infections, and cellulitis, and when taking into account recurrent episodes of infection. Limitations Outcome ascertainment relied on diagnostic codes at time of discharge. Conclusions Increasing provider awareness of CKD as a risk factor for infection is needed to reduce infection-related morbidity and mortality.

Infectious disease is recognized as an important complication among patients with end-stage renal disease, contributing to excess morbidity and health care costs. However, recent epidemiological studies have revealed that even mild to moderate stages of chronic kidney disease (CKD) substantially increase risk of infection. Regarding underlying mechanisms, evidence suggests various aspects of altered immune response in patients with CKD including impaired function of T cells, B cells and neutrophil. Multiple conditions surrounding CKD, such as older age, diabetes, and cardiovascular disease are important contributors in the increased susceptibility to infection in this population. In addition, several mechanisms impairing immune function have been hypothesized including accumulated uremic toxins, increased oxidative stress, endothelial dysfunction, low-grade inflammation, and mineral and bone disorders. In terms of prevention strategies, influenza and pneumococcal vaccines are most feasible and important. Nevertheless, the extent of vaccine utilization in CKD has not been well documented. In addition, antibody response to vaccination may be reduced in CKD patients, and thus a vaccine delivery strategy (e.g., dose and frequency) may need to be optimized among patients with CKD. Through this review, we demonstrate that infection is a major but underrecognized complication of CKD. As CKD is recognized as a serious public health issue, dedicated research is needed to better characterize the burden of infectious disease associated with CKD, understand the pathophysiology of infection in patients with CKD, and develop effective strategies to prevent infection and its sequela in this high risk population.

Background Acute infections are known cardiovascular disease ( CVD ) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in‐ and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings. A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14‐day odds ratio [ OR ]=12.83 [5.74, 28.68], 30‐day OR =8.39 [4.92, 14.31], 42‐day OR =6.24 [4.02, 9.67], and 90‐day OR =4.48 [3.18, 6.33]) and outpatient infections (14‐day OR =3.29 [2.50, 4.32], 30‐day OR =2.69 [2.14, 3.37], 42‐day OR =2.45 [1.97, 3.05], and 90‐day OR =1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods ( P <0.05). Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant ( P <0.10) for the 42‐ and 90‐day time periods. Conclusions In‐ and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis.

Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 is uncertain, in part, because of potential confounding by age and sex.Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19).Using random-effects models, we pooled relative risk (RR) estimates and conducted metaregression analyses.Results: Of the 373 publications identified in our search, 15 papers met our inclusion criteria, with 51,845 COVID-19 patients including 9,066 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 vs. <50 years. Two studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors significantly associated with severe COVID-19 were male sex (14 studies; pooled RR=1.70, [95%CI 1.52-1.89]), hypertension (10 studies; 2.74 [2.12-3.54]), diabetes (11 studies; 2.81 [2.01-3.93]), and CVD (9 studies; 3.58 [2.06-6.21]). RR for male sex was likely to be independent of age. Meta-regression analyses were suggestive of confounding by age for the other three factors. Only two studies reported multivariable analysis, with one showing non-significant association for CVD and the other demonstrating adjusted RR ~2 for hypertension and diabetes. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19.Conclusions: In addition to older age and male sex, hypertension, diabetes, and CVD were associated in univariate analyses with severe COVID-19. Although there is still uncertainty

Individuals with even mild to moderate CKD warrant clinical attention regarding the risk of hospitalization with GI bleeding.

This region-representative health care study finds an excess community-acquired infections incidence in individuals with mild to severe CKD. Lower respiratory tract infection, urinary tract infection, and sepsis are major infections in CKD.

BackgroundReduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin‐to‐creatinine ratio (ACR) individually increase risk of cardiovascular disease (CVD). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels.Methods and ResultsUsing 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996–1998, we explored the cross‐sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12 g/dL in women) and 7.2% had high hemoglobin (≥16 g/dL in men and ≥15 g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59–2.82) for eGFR 30 to 59 compared with ≥90 mL/min per 1.73 m2 and 1.45 (1.07–1.95) for ACR ≥30 compared with <10 mg/g. ACR ≥30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12–2.19] compared with <10 mg/g). During follow‐up, there were 1069 incident CVDs among 5098 CVD‐free participants at baseline. In multivariable Cox models, lower eGFR, higher ACR, and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia (P‐for‐interaction, 0.072). There was no hemoglobin‐ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin (P‐for‐interaction, 0.074).ConclusionsKidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.