The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis

BackgroundWhether 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. MethodsWe 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. ResultsOf 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 vs. <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. ConclusionsDespite 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 used to inform objective decisions on COVID-19 testing, clinical management, and workforce planning.

The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES@#The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population.@*METHODS@#We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models.@*RESULTS@#A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased.@*CONCLUSION@#A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES: The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population. METHODS: We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models. RESULTS: A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased. CONCLUSION: A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

The Relationship Between Serum Lipids and Depression

OBJECTIVE: Low cholesterol is associated with depression among western countries. The objective of this study was to examine the relationship between cholesterol and depression in Korean population with low levels of serum cholesterol. METHODS: The data of about 740,000 individuals, aged 30-64 years at entry in the Korean Cancer Prevention Study, were used. Total cholesterol levels were measured in 1992. Depression was measured using the modified DSM-IV (Diagnostic Criteria of Major Depressive Episode in Diagnostic and Statistical Manual of Mental Disorders-IV) scale. Total cholesterol was classified into four groups (quartile). Odds Ratios of low level of cholesterol were evaluated using multi-variable logistic models. RESULTS: The prevalence of major depression was 7.7% in men and 10.4% in women. After adjustment for various confounding variables, an inverse association was detected between cholesterol levels and depression intensity among men and women. The odds ratio (95% confidence interval) of the lowest quartile of cholesterol was 1.16 (1.13-1.20) on major depression compared with the highest quartile of cholesterol in men. The corresponding odds ratio among women was 1.09 (1.04-1.15). The strongest association among 9 items of depression was found at "decreased appetite and lost weight" in both men (OR=1.68) and women (OR=1.43). CONCLUSION: Low cholesterol is associated with major depression in men and women. Further studies are necessary to evaluate the cross-validation, to explore the biological mechanism, and to identify the clinical implication.

Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study

BACKGROUND: Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. METHODS: A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. RESULTS: Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. CONCLUSION: A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.