Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.

AIM: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, 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 CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (pinteraction = 0.017, 0.033 and 0.014, respectively). CONCLUSION: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

Smoking timing, genetic susceptibility, and the risk of incident atrial fibrillation: a large prospective cohort study.

AIMS: Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with risk of incident AF, and test the modification effect of genetic susceptibility. METHODS AND RESULTS: A total of 305,627 participants with detailed information for time from waking to first cigarette were enrolled from UK Biobank database. Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. Weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13,410 AF cases were documented. Compared to non-smokers, time from waking to the first cigarette showed gradient inverse associations with risk of incident AF (P-trend <0.001). The adjusted hazard ratio related to smoking timing was 1.13 (95% CI: 0.96-1.34) for >120 minutes, 1.20 (95% CI: 1.01-1.42) for 61-120 minutes, 1.34 (95% CI: 1.19-1.51) for 30-60 minutes, 1.43 (95% CI: 1.26-1.63) for 5-15 minutes, and 1.49 (95% CI: 1.24-1.63) for <5 minutes, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF. CONCLUSIONS: Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF.

Our study aimed to analyze the relationship between the time from waking to the first cigarette and incidence of AF, and the modification role of genetic susceptibility.Shorter time from waking to the first cigarette was related to elevated risk of incident atrial fibrillation.Genetic susceptibility to atrial fibrillation strengthened the gradient inverse association of time from waking to the first cigarette with incidence of AF.

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 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.

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.

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.