Smoking timing, genetic susceptibility and the risk of incident type 2 diabetes: A cohort study from the UK Biobank.

AIM: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. MATERIALS AND METHODS: A total of 294 815 participants without diabetes from the UK Biobank, including non-smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. RESULTS: During a median follow-up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non-smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend < .001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17-1.81) for more than 2 hours, 1.51 (1.21-1.87) for 1-2 hours, 1.58 (1.34-1.85) for 30-60 minutes, 1.86 (1.57-2.21) for 5-15 minutes and 2.01 (1.60-2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52-2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P-interaction = .51). CONCLUSIONS: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D.

Degree of joint risk factor control and hazard of mortality in diabetes patients: a matched cohort study in UK Biobank.

BACKGROUND: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. METHODS: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. RESULTS: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41-0.62), 74% (HR 0.26, 95% CI 0.16-0.43) and 38% (HR 0.62, 95% CI 0.44-0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. CONCLUSIONS: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality.

Degree of Risk Factor Control and Incident Cardiovascular Diseases in Patients With Hypertension.

OBJECTIVE: To investigate whether joint risk factor control could reduce the excess risk of cardiovascular disease (CVD) in patients with hypertension. PATIENTS AND METHODS: A total of 75,293 patients with diagnosed hypertension from the UK Biobank study were included, matched with 256,619 nonhypertensive controls, and followed up until May 31, 2021. Seven risk factors were measured to define joint risk factor control, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. RESULTS: Among hypertensive patients, 14% to 24% lower risks of CVD outcomes were associated with each additional risk factor control. In the Cox proportional hazards models, adjusted hazard ratios for patients with 6 or more risk factor controls compared with patients having 2 or less risk factor controls were 0.49 (95% CI, 0.45 to 0.55) for CVD, 0.51 (95% CI, 0.45 to 0.57) for coronary heart disease, 0.48 (95% CI, 0.38 to 0.60) for stroke, and 0.34 (95% CI, 0.26 to 0.44) for CVD mortality. The excess risks of CVD outcomes in patients with hypertension were diminished to nonsignificant or even lower compared with controls if achieving 6 or more risk factor controls. Men experienced stronger protective associations of joint risk factor control on risks of CVD than women (P<.001 for interaction). CONCLUSION: The joint risk factor control is associated with lower risks of CVD, and a high degree of risk factor control may considerably attenuate the excess risk of CVD among patients with hypertension.

Self-Reported Frequency of Adding Salt to Food and Risk of Incident Chronic Kidney Disease.

Importance: The self-reported frequency of adding salt to foods could reflect a person's long-term salt taste preference, and salt intake has been associated with increased risk of cardiovascular diseases (CVD). Whether self-reported adding of salt to foods is associated with increased risk of chronic kidney disease (CKD) remains unknown. Objective: To prospectively examine the association of self-reported frequency of adding salt to foods with incident CKD risk in a general population of adults. Design, Setting, and Participants: This population-based cohort study evaluated UK Biobank participants aged 37 to 73 years who were free of CKD at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Data were analyzed from October 2022 to April 2023. Exposure: Self-reported frequency of adding salt to foods, categorized into never or rarely, sometimes, usually, and always. Main Outcome and Measure: Incident CKD cases were defined by diagnostic codes. Hazard ratios (HRs) and 95% CIs were calculated by using Cox proportional hazards models. Models were adjusted for several potential confounders including age, sex, race and ethnicity, Townsend Deprivation Index, estimated glomerular filtration rate (eGFR), body mass index, (BMI), smoking status, alcohol drinking status, regular physical activity, high cholesterol, diabetes, CVD, hypertension, infectious disease, immune disease, and nephrotoxic drugs use at baseline. Results: Within a cohort of 465 288 individuals (mean [SD] age 56.32 [8.08] years; 255 102 female participants [54.83%]; 210 186 male participants [45.17%]), participants with higher self-reported frequency of adding salt to foods were more likely to have a higher BMI, higher Townsend Deprivation Index score, and diminished baseline eGFR compared with those who reported a lower frequency of adding salt to foods. Participants who added salt to their foods were also more likely than those who did not add salt to their foods to be current smokers and have diabetes or CVD at baseline. During a median (IQR) follow-up of 11.8 (1.4) years, 22 031 incident events of CKD were documented. Higher self-reported frequency of adding salt to foods was significantly associated with a higher CKD risk after adjustment for covariates. Compared with those who reported never or rarely adding salt to foods, those who reported sometimes adding salt to food (adjusted HR [aHR], 1.04; 95% CI, 1.00-1.07), those who reported usually adding salt to food (aHR, 1.07; 95% CI, 1.02-1.11), and those who reported always adding salt to food (aHR, 1.11; 95% CI, 1.05-1.18) had an increased risk of CKD (P for trend < .001). In addition, eGFR, BMI, and physical activity significantly modified the associations, which were more pronounced among participants with a higher eGFR, lower BMI, or lower level of physical activity. Conclusions and Relevance: In this cohort study of 465 288 individuals, a higher self-reported frequency of adding salt to foods was associated with a higher risk of CKD in the general population. These findings suggest that reducing the frequency of adding salt to foods at the table might be a valuable strategy to lower CKD risk in the general population.

Dietary Sodium Intake and Risk of Incident Type 2 Diabetes.

OBJECTIVE: To fill the knowledge gap of the relation between long-term dietary sodium intake and type 2 diabetes (T2D), we evaluate the association between the frequency of adding salt to foods, a surrogate marker for evaluating the long-term sodium intake, and incident T2D risk. METHODS: A total of 402,982 participants from UK Biobank (March 13, 2006 - October 10, 2010) who were free of diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline, and had completed information on adding salt were analyzed in this study. RESULTS: During a median of 11.9 years of follow-up, 13,120 incident cases of T2D were documented. Compared with participants who "never/rarely" added salt to foods, the adjusted HRs were 1.11 (95% CI, 1.06 to 1.15), 1.18 (95% CI, 1.12 to 1.24), and 1.28 (95% CI, 1.20 to 1.37) across the groups of "sometimes," "usually," and "always," respectively (P-trend<.001). We did not find significant interactions between the frequency of adding salt to foods and baseline hypertension status and other covariates on the risk of incident T2D. The observed positive association was partly mediated by body mass index, waist to hip ratio, and C-reactive protein, with a significant mediation effect of 33.8%, 39.9%, and 8.6%, respectively. The significant mediation effect of body mass index was largely driven by the body fat mass rather than the body fat-free mass. CONCLUSION: Our findings for the first time indicate that higher frequency of adding salt to foods, a surrogate marker for a person's long-term salt taste preference and intake, is associated with a higher T2D risk.

DNA Methylation at ABCG1 and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial.

OBJECTIVE: To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight loss interventions with long-term changes in adiposity and body fat distribution. RESEARCH DESIGN AND METHODS: The current study included overweight/obese participants from the POUNDS Lost trial. Blood levels of regional DNA methylation at ABCG1 were profiled by high-resolution methylC-capture sequencing at baseline among 673 participants, of whom 598 were followed up at 6 months and 543 at 2 years. Two-year changes in adiposity and computed tomography-measured body fat distribution were calculated. RESULTS: Regional DNA methylation at ABCG1 showed significantly different associations with long-term changes in body weight and waist circumference at 6 months and 2 years in dietary interventions varying in protein intake (interaction P < 0.05 for all). Among participants assigned to an average-protein (15%) diet, lower baseline regional DNA methylation at ABCG1 was associated with greater reductions in body weight and waist circumference at 6 months and 2 years, whereas opposite associations were found among those assigned to a high-protein (25%) diet. Similar interaction patterns were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (interaction P < 0.05 for all). CONCLUSIONS: Baseline DNA methylation at ABCG1 interacted with dietary protein intake on long-term decreases in adiposity and body fat distribution. Participants with lower methylation at ABCG1 benefitted more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.

DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressure in Response to Weight-Loss Diets in the POUNDS Lost Trial.

BACKGROUND: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. METHODS: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. We defined the regional DNAm levels as the average methylation level of 5'-cytosine-phosphate-guanine-3' within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793), respectively. Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. RESULTS: The regional DNAm at LINC00319, showed significantly different associations with 2-year changes in systolic blood pressure and diastolic blood pressure among participants assigned to low- or high-fat diets (P for interaction<0.05 for all). In response to the low-fat diet, per SD higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in systolic blood pressure (ß, -1.481; P=0.020) and diastolic blood pressure (ß, -1.096; P=0.009). Three trajectories of changes in systolic blood pressure or diastolic blood pressure were identified, and participants with higher regional DNAm at LINC00319 were more likely to experience and maintain decreased systolic blood pressure and diastolic blood pressure (odds ratio of being in decrease-stable versus stable [95% CI], 1.542 [1.146-2.076] and 1.463 [1.125-1.902]). CONCLUSIONS: Our findings suggest that DNAm could be a metabolic memory bridging early and later life, and an indicator of more benefits from eating a low-fat weight-loss diet.

Degree of Joint Risk Factor Control and Incident Heart Failure in Hypertensive Patients.

BACKGROUND: Heart failure (HF) is a major complication in patients with hypertension. OBJECTIVES: This study aimed to investigate the extent to which joint risk factor control could attenuate hypertension-related excess risk of HF. METHODS: The study included a total of 75,293 participants with diagnosed hypertension from the UK Biobank and matched with 256,619 nonhypertensive control subjects, followed up until May 31, 2021. The degree of joint risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of HF. RESULTS: Among hypertensive patients, joint risk factor control showed an association with a stepwise reduction of incident HF risk. Each additional risk factor control was related to a 20% lower risk, and the optimal risk factor control (controlling ≥6 risk factors) was associated with a 62% lower risk (HR: 0.38; 95% CI: 0.31-0.45). In addition, the study found that the hypertension-related excess risk of HF among participants jointly controlling ≥6 risk factors were even lower than in nonhypertensive control subjects (HR: 0.79; 95% CI: 0.67-0.94). The protective associations of joint risk factor control and risk of incident HF were broadly stronger among men than women and among medication users than nonusers (P for interaction < 0.05). CONCLUSIONS: The joint risk factor control is associated with a lower risk of incident HF in an accumulative and sex-specific manner. Optimal risk factor control may eliminate hypertension-related excess risk of HF.

DNA Methylation Near CPT1A and Changes in Triglyceride-rich Lipoproteins in Response to Weight-loss Diet Interventions.

CONTEXT: Carnitine palmitoyltransferase-1A, encoded by the CPT1A gene, plays a key role in the oxidation of long-chain fatty acids in the mitochondria and may be important in triglyceride metabolism. Previous work has shown that high fat intake was negatively associated with CPT1A methylation and positively associated with CPT1A expression. OBJECTIVE: We aim to investigate the association of DNA methylation (DNAm) at the CPT1A gene with reductions in triglycerides and triglyceride-rich lipoproteins (TRLs) in response to weight-loss diet interventions. METHODS: The current study included 538 White participants, who were randomly assigned to 1 of 4 diets varying in macronutrient components. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 triglyceride-related DNAm sites. RESULTS: Dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss. Among participants assigned to a low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years (P = .01), compared with those assigned to a high-fat diet (P = .64) (P interaction = .018). Further investigation on lipids and apolipoproteins in very low-density lipoprotein (VLDL) revealed similar interaction patterns for 2-year changes in VLDL-triglycerides, VLDL-cholesterol, and VLDL-apolipoprotein B (P interaction = .009, .002, and .016, respectively), but not for VLDL-apoC-III (P interaction = .36). CONCLUSION: Participants with a higher regional DNAm level at CPT1A benefit more in long-term improvement in triglycerides, particularly in the TRLs and related apolipoproteins when consuming a low-fat weight-loss diet.

Echocardiography-Based Cardiac Structure Parameters for the Long-term Risk of End-Stage Kidney Disease in Black Individuals: The Atherosclerosis Risk in Communities Study.

OBJECTIVE: To assess whether echocardiographic parameters of left ventricular (LV) structure and function relate to the long-term risk of incident end-stage kidney disease (ESKD). PATIENTS AND METHODS: We conducted a prospective cohort study analyzing 2137 Black participants from the Jackson site of the Atherosclerosis Risk in Communities Study from January 1, 1993, through July 31, 2017. Echocardiographic parameters of LV structure and function were obtained from 1993 to 1995. The primary outcome incident ESKD was identified through the linkage to the United States Renal Data System. Cox proportional hazards models were used to estimate the hazard ratios (HRs) according to each echocardiographic parameter. RESULTS: There were 117 incident ESKD cases during a median follow-up of 22.2 (interquartile range, 15.0-23.3) years. Multivariable Cox models revealed that a higher LV mass index was significantly associated with the risk of ESKD (HR, 2.38; 95% CI, 1.21 to 4.68 for highest vs lowest quartile, P = 0.012). The HRs were significant and even higher for LV posterior wall thickness, with slightly higher HRs when their measures in end-systole (HR for highest vs lowest quartile, 4.38; 95% CI, 1.94 to 9.92, P < 0.001) vs end-diastole (HR, 3.50; 95% CI, 1.53 to 8.01, P = 0.003) were used. The associations were not significant for LV function parameters. CONCLUSION: In Black individuals residing in the community, echocardiographic parameters of LV structure, including LV wall thickness, were robustly associated with the risk of subsequently incident ESKD. These results have potential implications for novel prevention and management strategies for persons with abnormal LV structure.

Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996-1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018-2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34-2.47), CAC (aOR, 1.40; 95% CI, 1.08-1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07-1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06-1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05-1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Simplified hypertension screening approaches with low misclassification and high efficiency in the United States, Nepal, and India.

Standard triplicate blood pressure (BP) measurements pose time barriers to hypertension screening, especially in resource-limited settings. We assessed the implications of simplified approaches using fewer measurements with adults (≥18 years old) not using anti-hypertensive medications from the US National Health and Nutrition Examination Survey 1999-2016 (n = 30 614), and two datasets from May Measurement Month 2017-2018 (n = 14 795 for Nepal and n = 6 771 for India). We evaluated the proportion of misclassification of hypertension when employing the following simplified approaches: using only 1st BP, only 2nd BP, 2nd if 1st BP in a given range (otherwise using 1st), and average of 1st and 2nd BP. Hypertension was defined as average of 2nd and 3rd systolic BP ≥140 and/or diastolic BP ≥90 mm Hg. Using only the 1st BP, the proportion of missed hypertension ranged from 8.2%-12.1% and overidentified hypertension from 4.3%-9.1%. Using only 2nd BP reduced the misclassification considerably (corresponding estimates, 4.9%-6.4% for missed hypertension and 2.0%-4.4% for overidentified hypertension) but needed 2nd BP in all participants. Using 2nd BP if 1st BP ≥130/80 demonstrated similar estimates of missed hypertension (3.8%-8.1%) and overidentified hypertension (2.0%-3.9%), but only required a 2nd BP in 33.8%-59.8% of participants. In conclusion, a simplified approach utilizing 1st BP supplemented by 2nd BP in some individuals has low misclassification rates and requires approximately half of the total number of measurements compared to the standard approach, and thus can facilitate screening in resource-constrained settings.

Cardiovascular Disease and Coronavirus Disease 2019: Epidemiology, Management, and Prevention.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has become a global pandemic associated with significant morbidity and mortality. This review summarizes findings up to date on the relationship between cardiovascular disease (CVD) and COVID-19. RECENT FINDINGS: Preexisting CVD is a common condition among patients with COVID-19 and is associated with increased disease severity and mortality. Conversely, COVID-19 has various clinical manifestations on cardiovascular system, including thrombotic events and cardiac dysfunction. The pandemic has impacted healthcare utilization among patients with CVD, which may have led to potential delay in access to the healthcare system during acute events not directly COVID-19-related. SUMMARY: While COVID-19 vaccine is being developed and distributed, controlling CVD risk factors and adherence to recommendations of existing immunization (e.g., influenza vaccine) are key in protecting the health of individuals with CVD during the COVID-19 pandemic. Further research is needed to understand the epidemiological and pathophysiological basis for the interaction between CVD and COVID-19.

Conventional and Novel Lipid Measures and Risk of Peripheral Artery Disease.

OBJECTIVE: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. CONCLUSIONS: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.

The Relationship of COVID-19 Severity with Cardiovascular Disease and Its Traditional Risk Factors: A Systematic Review and Meta-Analysis.

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.

Cardiorespiratory responses to fine particles during ambient PM2.5 pollution waves: Findings from a randomized crossover trial in young healthy adults.

BACKGROUND: PM2.5 pollution waves (PPWs) are severe air pollution events with extremely high-level concentration of ambient PM2.5. PPWs, such as haze days, were suggested to be associated with increased cardiopulmonary mortality and morbidity. However, the biological mechanism response to ambient PM2.5 during PPWs is still unclear. METHODS: A randomized crossover trial was conducted on 29 healthy young adults. Repeated health measurements were performed before, during and after two typical PPWs under filtered and sham indoor air purification, with a washout interval of at least 2 weeks. Health parameters including blood pressure (BP), pulmonary function, fractional exhaled nitric oxide (FeNO) and circulating biomarkers which reflect platelet activation, blood coagulation and systematic oxidative stress were measured. RESULTS: Ambient PM2.5 levels elevated apparently during PPWs. Under sham purification, significant increase in FeNO and soluble P-selectin (sP-selectin) and decreases in pulmonary function were observed from pre-PPWs period to during-PPWs period. The changes in health biomarkers as mentioned above became attenuated and insignificant under filtered condition. For instance, sP-selectin increased by 12.0% (95% CI: 3.8%, 20.8%) during-PPWs periods compared with pre-PPWs periods under sham purification, while non-significant change was observed under filtered condition. Significant associations between time-weighted personal PM2.5 exposure and increased levels of health biomarkers including FeNO, sP-selectin, oxidized low-density lipoprotein (ox-LDL) and 8-isoprostane (8-isoPGF2α) were found. CONCLUSION: PPWs could affect cardiopulmonary health through systematic oxidative stress, platelet activation and respiratory inflammation in healthy adults, and short-term indoor air purification could alleviate the adverse cardiopulmonary effects.

Brachial-Ankle Pulse Wave Velocity is Associated with the Risk of New Carotid Plaque Formation: Data from a Chinese Community-based Cohort.

Artery stiffness is an independent marker for atherosclerotic cardiovascular diseases. However, whether the brachial-ankle pulse wave velocity (ba-PWV) is related to new carotid plaque formation is unresolved. This study aimed to investigate the association between baseline ba-PWV and new carotid plaque formation in a Chinese community-based population without carotid plaques at baseline. This study population consisted of a total of 738 participants from an atherosclerosis cohort in Beijing, China. After a mean 2.3-year follow-up, the incidence of carotid plaques were 21.2% and 36.5% in the groups with ba-PWV < 1,400 cm/s and ≥1,400 cm/s, respectively. Compared with baseline ba-PWV < 1,400 cm/s group, ba-PWV ≥ 1,400 cm/s group was significantly associated with the incidence of new carotid plaque formation (odds ratio [OR] = 2.14, 95% CI: 1.50-3.03, P < 0.01), even after adjusting for common risk factors (OR = 1.52, 95% CI: 1.02-2.25, P = 0.04). Furthermore, there was a strong relationship between baseline ba-PWV and carotid plaque formation in subjects with ba-PWV < 1,400 cm/s, but no such relationship was found in subjects with baseline ba-PWV ≥ 1,400 cm/s. In conclusion, this study suggests that baseline ba-PWV is independently associated with the risk of carotid plaque formation in a Chinese community-based population.

Joint Effect of Non-invasive Central Systolic Blood Pressure and Peripheral Systolic Blood Pressure on Incident Hypertension in a Chinese Community-based Population.

Central blood pressure level is not always consistent with peripheral blood pressure level, and especially their joint effect on incident hypertension is not well established. A total of 1607 non-hypertensive subjects from an atherosclerosis cohort in Beijing, China were included. Central systolic blood pressure (cSBP) was obtained using Omron HEM-9000AI machine and peripheral systolic blood pressure (pSBP) was measured using Omron HEM-7117 electronic sphygmomanometer, separately. Hypertension was defined as BP ≥ 140/90 mmHg or self-reported hypertension or taking any antihypertension drugs at the follow-up survey. After a median follow-up of 2.3 years, incident hypertension was 13.1%. Every 1 standard deviation increase of cSBP and pSBP was associated with 1.98 (95%CI: 1.69-2.33) and 2.84 (95%CI: 2.30-3.52) times of incident hypertension after adjustment for confounders. Moreover, hypertension risk in single pSBP ≥ 120 mmHg group, single cSBP ≥ 120 mmHg group, and both pSBP and cSBP ≥ 120 mmHg group was 2.83 (95%CI: 0.98-8.16), 3.28 (95%CI: 1.24-8.70), and 11.47 (95%CI: 4.97-26.46) times higher than both pSBP and cSBP < 120 mmHg group, respectively. The joint effect of cSBP and pSBP is superior to either cSBP or pSBP to predict incident hypertension in a Chinese community-based population. Screening of central blood pressure should be considered in non-hypertensive population for the purpose of primary intervention, especially for subjects with pSBP ≥ 120 mmHg.