Hazard Ratios For Cardiovascular Disease Mortality Research Articles

Polygenic risk score for blood pressure and lifestyle factors with overall and CVD mortality: a prospective cohort study in a Japanese population.

Although previous polygenic risk score (PRS) studies for cardiovascular disease (CVD) focused on incidence, few studies addressed CVD mortality and quantified risks by environmental exposures in different genetic liability groups. This prospective study aimed to examine the associations of blood pressure PRS with all-cause and CVD mortality and to quantify the attributable risk by modifiable lifestyles across different PRS strata. 9,296 participants in the Japan Multi-Institutional Collaborative Cohort Study without hypertension at baseline were analyzed in this analysis. PRS for systolic blood pressure and diastolic blood pressure (PRSSBP and PRSDBP) were developed using publicly available Biobank Japan GWAS summary statistics. CVD-related mortality was defined by the International Classification of Diseases 10th version (I00-I99). Cox-proportional hazard model was used to examine associations of PRSs and lifestyle variables (smoking, drinking, and dietary sodium intake) with mortality. During a median 12.6-year follow-up period, we observed 273 all-cause and 41 CVD mortality cases. Compared to the middle PRS group (20-80th percentile), adjusted hazard ratios for CVD mortality at the top PRS group ( > 90th percentile) were 3.67 for PRSSBP and 2.92 for PRSDBP. Attributable risks of CVD mortality by modifiable lifestyles were higher in the high PRS group ( > 80th percentile) compared with the low PRS group (0-80th percentile). In summary, blood pressure PRS is associated with CVD mortality in the general Japanese population. Our study implies that integrating PRS with lifestyle could contribute to identify target populations for lifestyle intervention even though improvement of discriminatory ability by PRS alone is limited.

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

ObjectiveAlthough blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia.MethodsThis analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used.ResultsDuring the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis.ConclusionsThis study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Trends in All-Cause, Cardiovascular, and Noncardiovascular Mortality Among US Adults With Hypertension.

Death certificate data indicate that hypertension may have increased as a contributing cause of death among US adults. Hypertension is not commonly recorded on death certificates although it contributes to a substantial proportion of cardiovascular disease (CVD) deaths. We estimated changes in all-cause, CVD, and non-CVD mortality over 5 years of follow-up among 4 cohorts of US adults with hypertension using mortality follow-up data from National Health and Nutrition Examination Survey III in 1988 to 1994, and National Health and Nutrition Examination Survey cycles from 1999 to 2000 through 2015 to 2016 (n=20 927). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or antihypertensive medication use. Participants were grouped according to the date of their National Health and Nutrition Examination Survey study visit (1988-1994, 1999-2004, 2005-2010, 2011-2016). There were 2646, 1048, and 1598 all-cause, CVD, and non-CVD deaths, respectively. After age, gender, and race/ethnicity adjustment and compared with the 1988 to 1994 cohort, the hazard ratio of all-cause mortality was 0.88 (95% CI, 0.76-1.01) for the 1999 to 2004 cohort, 0.82 (95% CI, 0.70-0.95) for the 2005 to 2010 cohort, and 0.89 (95% CI, 0.75-1.05) for the 2011 to 2016 cohort (P trend=0.123). The age, gender, and race/ethnicity-adjusted hazard ratios for CVD mortality compared with the 1988 to 1994 cohort were 0.74 (95% CI, 0.60-0.90) for the 1999 to 2004 cohort, 0.61 (95% CI, 0.50-0.74) for the 2005 to 2010 cohort, and 0.57 (95% CI, 0.44-0.74) for the 2011 to 2016 cohort (P trend <0.001). There was no evidence of a change in CVD mortality between the 2005 to 2010 and 2011 to 2016 cohorts (P=0.661). Noncardiovascular mortality did not decline over the study period (P trend=0.145). The decline in CVD mortality among US adults with hypertension stalled after 2005 to 2010.

Prevalence of prediabetes and risk of CVD mortality in individuals with prediabetes alone or plus hypertension in Northeast China: insight from a population based cohort study

BackgroundTo evaluate the current prevalence of prediabetes in northeast China, and further determine the association between prediabetes alone or coexistent with hypertension and cardiovascular disease (CVD) mortality.MethodsIn the prospective study, 15,557 participants without diabetes among aged ≥40 years in northeast China, were followed for a median of 5.5 years. Following the American Diabetes Association, prediabetes was defined as fasting plasma glucose (FPG) range of 5.6-6.9 mmol/L or glycated hemoglobin (HbA1c) range of 5.7-6.4% in people without diabetes.ResultsThe prevalence of prediabetes was 44.3% among population aged ≥40 years in northeast China. Prediabetes alone did not promote risk of CVD mortality. However, when the subgroups were stratified by hypertension, the CVD mortality risk in prediabetes plus hypertension subjects increased significantly compared with population without prediabetes and hypertension. Multivariate-adjusted hazard ratios for CVD mortality in prediabetes subgroups plus hypertension were 2.28 (95% CI: 1.50, 3.47) for those diagnosed by FPG < 5.6 mmol/L & HbA1c 5.7-6.4%, 2.18 (95% CI: 1.53, 3.10) for those diagnosed by FPG 5.6-6.0 mmol/L & HbA1c < 6.5% and 2.35 (95% CI: 1.65, 3.35) for those diagnosed by FPG 6.1-6.9 & HbA1c < 6.5% compared with the reference group. Moreover, the percentage of hypertension in prediabetes subjects was high (60.4%), but the awareness, treatment and control rates were far from satisfactory (45.3, 35.1 and 4.8%, respectively).ConclusionsThe prevalence of prediabetes remains high in northeast China, and the CVD mortality was elevated significantly in prediabetes coexistent with hypertension. Considering the high percentage and low control rate of hypertension in prediabetes, strategies focused on HbA1c screening, FPG lowering and blood pressure management should be emphasized in northeast China.

Hypertension in the first blood pressure reading and the risk of cardiovascular disease mortality in the general population: findings from the prospective KORA study.

The risk of cardiovascular disease (CVD) mortality in individuals with an alerting reaction, assessed by hypertension in the first blood pressure (BP) reading but normal BP in further readings, remains unknown in the general population. In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1 years (SD ± 12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7 years (SD ± 7.05 years; max: 32 years; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32 cases/10 000 person-years), but lower than hypertension (118 cases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P = 0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P = 0.06]. The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals.

Associations between dietary pesticide residue mixture exposure and mortality in a population-based prospective cohort of men and women

BackgroundThere is a concern that pesticide residues, regularly detected in foods, might pose a health risk to the consumer, but epidemiological evidence is limited. We assessed the associations between dietary exposure to a mixture of pesticide residues and mortality. MethodsFood consumption was assessed in 68,844 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men, 45–83 years at baseline (1997). Concentrations of pesticide residues detected in foods on the Swedish market (1996–1998), mainly fruits and vegetables, were obtained via monitoring programs. To assess mixture effects, we summed per food item the ratios of each single pesticide mean residue concentration divided by its acceptable daily intake to create for each participant a Dietary Pesticide Hazard Index (adjusted for energy intake and expressed per kilogram of body weight). Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 %CI). ResultsDuring 15 years of follow-up (1998–2014), a total of 16,527 deaths occurred, of which 6,238 were caused by cardiovascular disease (CVD) and 5,364 by cancer. Comparing extreme quintiles of Dietary Pesticide Hazard Index, the highest category was inversely associated with CVD mortality HR, 0.82 (95 % CI, 0.75–0.90) and with cancer mortality HR 0.82 (95 % CI 0.75–0.91). In analyses stratified by high/low Dietary Pesticide Hazard Index, similar inverse associations were observed by increasing fruit and vegetable consumption. ConclusionsWe observed no indications that dietary exposure to pesticide residue mixtures was associated with increased mortality, nor any clear indications that the benefits of fruit and vegetable consumption on mortality was compromised. Yet, our results need to be interpreted with caution.

Diet quality and long-term cardiovascular mortality after myocardial infarction in the Alpha Omega Cohort

Abstract Introduction A healthy diet is important for the prevention and treatment of cardiovascular disease (CVD). The Dutch Health Council recently defined dietary guidelines for patients with atherosclerotic CVD (ASCVD), which we investigated in relation to long-term mortality after myocardial infarction (MI). Purpose We developed the Dutch Healthy Diet index for CVD patients (DHD-CVD index) and examined its relation with mortality in post-MI patients. Methods We included 4,365 patients of the Dutch Alpha Omega Cohort (60-80 y, 80% male) with a MI &amp;lt;10 y prior to study enrolment. Dietary intake was assessed at baseline (2002-2006), using a validated 203-item food frequency questionnaire. To create the DHD-CVD index, the existing 2015 Dutch Healthy Diet index was adapted using the 2023 Dutch dietary guidelines for ASCVD patients (scale from 0 to maximal adherence [0-150]). Patients were followed for cause-specific mortality through December 2018. Hazard Ratios (HRs) across quartiles of the DHD-CVD-index (ref = Q1, i.e. low overall diet quality) and per 1-SD increment in score were estimated using Cox proportional hazard models. Associations were adjusted for age, sex, total energy intake, smoking, education and physical activity. Results were additionally stratified for sex, obesity and diabetes. Results Of the cohort, 17% smoked, 21% had diabetes and &amp;gt;90% used statins or other CVD drugs. During a follow-up of 48,660 person-years, 2,048 deaths occurred of which 911 were due to CVD. The mean DHD-CVD score was 78.9 (SD 13) points. High diet quality (Q4) was associated with a 29% lower risk of CVD mortality compared to low diet quality (HR: 0.71, 95% CI: 0.56, 0.84), with an HR of 0.88 (95% CI: 0.82, 0.94) per 1-SD. For all-cause mortality, we observed a 14% lower risk for high vs. low diet quality (HR: 0.86, 95% CI: 0.76, 0.98), with an HR of 0.94 (95% CI: 0.90, 0.98) per 1-SD. HRs did not essentially differ between male of female patients, or between obese and non-obese patients. HRs for CVD mortality were stronger in non-diabetic patients (HR: 0.86, 95% CI: 0.79, 0.93; per 1-SD), and no longer statistically significant in patients with diabetes (HR: 0.97, 95% CI: 0.84, 1.11; per 1-SD). Conclusion A high diet quality, measured with the DHD-CVD index, was associated with a lower risk of CVD and all-cause mortality after MI in Dutch patients. Adherence to dietary guidelines for CVD patients should be considered on top of medication use.

Associations of composite dietary antioxidant index with cardiovascular disease mortality among patients with type 2 diabetes

To investigate the associations of composite dietary antioxidant index (CDAI) with risk of cardiovascular disease (CVD) mortality among individuals with type 2 diabetes (T2D). This prospective cohort study included 7551 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2018. Death statistics were gathered by connecting the cohort database to the National Death Index through December 31, 2019. Multivariable Cox proportional hazards regression models were utilized to calculate hazard ratios and 95% CIs for the relationship of CDAI with risks of CVD and all-cause mortality. Three multivariable models were built. Restricted cubic spline analyses were utilized to explore the nonlinear association of CDAI with CVD mortality, and nonlinearity was tested by the likelihood ratio test. This cohort study included data from 7551 participants with T2D (mean [SE] age, 61.4 (0.2) years; 3811 male [weighted, 50.5%] and 3740 female [weighted, 49.5%]; median CDAI level, − 2.19 [IQR, − 2.19 ~ − 0.22]). A total of 2227 all-cause deaths and 746 CVD deaths were identified during an average of 98 months of follow-up. Nonlinear associations were observed for CDAI (P < 0.05 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the first quartile of CDAI levels (< − 2.19), the hazard ratios for CVD mortality were 0.47 (95% CI 0.30–0.75) for participants in the highest CDAI level quartile. This cohort study found that higher CDAI levels were significantly associated with lower risk of CVD mortality among individuals with T2D.

The effect of total cholesterol/high-density lipoprotein cholesterol ratio on mortality risk in the general population.

The relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and all-cause and cardiovascular mortality has not been elucidated. Herein, we intend to probe the effect of the TC/HDL-C ratio on all-cause and cardiovascular mortality in the general population. From the 1999-2014 National Health and Nutrition Examination Surveys (NHANES), a total of 32,405 health participants aged ≥18 years were included. The TC/HDL-C levels were divided into five groups: Q1: <2.86, Q2: 2.86-3.46, Q3: 3.46-4.12, Q4: 4.12-5.07, Q5: >5.07. Multivariate Cox regression models were used to explore the relationship between the TC/HDL-C ratio and cardiovascular and all-cause mortality. Two-piecewise linear regression models and restricted cubic spline regression were used to explore nonlinear and irregularly shaped relationships. Kaplan-Meier survival curve and subgroup analyses were conducted. The population comprised 15,675 men and 16,730 women with a mean age of 43 years. During a median follow-up of 98 months (8.1 years), 2,859 mortality cases were recorded. The TC/HDL-C ratio and all-cause mortality showed a nonlinear association after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause mortality were particularly positively related to the level of TC/HDL-C ratio in the higher range >5.07 and in the lower range <2.86 (HR 1.26; 95% CI 1.10, 1.45; HR 1.18; 95% CI 1.00, 1.38, respectively), although the HRs of cardiovascular disease mortality showed no difference among the five groups. In the two-piecewise linear regression model, a TC/HDL-C ratio range of ≥4.22 was positively correlated with cardiovascular mortality (HR 1.13; 95% CI 1.02, 1.25). In the subgroup analysis, a nonlinear association between TC/HDL-C and all-cause mortality was found in those aged <65 years, men, and the no lipid drug treatment population. A nonlinear association between the TC/HDL-C ratio and all-cause mortality was found, indicating that a too-low or too-high TC/HDL-C ratio might increase all-cause mortality. However, for cardiovascular mortality, it does not seem so. The cutoff value was 4.22. The individuals had higher cardiovascular mortality with a TC/HDL-C ratio >4.22.

The synergistic effect of depression and moderate chronic kidney disease on the all-cause and cardiovascular disease mortality among adults: a retrospective cohort study

BackgroundThe relationship between the coexistence of depression and moderate chronic kidney disease (CKD) and mortality is unclear. We aimed to investigate whether there is a synergistic effect of depression and moderate CKD on the all-cause and cardiovascular disease (CVD) mortality among adults.MethodsWe studied 24,412 participants from the National Health and Nutrition Examination Survey 2005–2014 with a mortality follow-up assessment in 2015. Four groups were created based on depression and CKD status: Group 1, no depression and no CKD; Group 2, depression present and no CKD; Group 3: no depression and CKD present; Group 4: depression present and CKD present. Moderate CKD was defined as an estimated glomerular filtration rate of 15–59 mL/min/1.73 m2 (Stage 3–4) or one-time urine albumin-to-creatinine ratio ≥ 30 mg/g. Depression was defined as the 9-item Patient Health Questionnaire score of 10 or more. Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratios (HRs) of death for Group 4 with other groups.ResultsOver a mean follow-up of 5.8 years, 1783 deaths were documented, including 338 deaths from CVD. The HR for all-cause mortality in Group 4 was 3.62 (95% CI: 2.69–4.87), 2.99 (1.92–4.66), and 1.75 (1.29–2.37) when compared with Group 1, 2, and 3, respectively. The HR for CVD mortality in Group 4 was 3.89 (1.68–9.00), 1.90 (0.86–4.21), and 1.97 (1.17–3.32) when compared with Group 1, 2, and 3, respectively.ConclusionsThere might be a synergistic effect of depression and moderate CKD on all-cause mortality. Moreover, depression might increase the risk of CVD mortality in individuals with moderate CKD.

Long-term cardiovascular mortality in women with twin pregnancies by lifetime reproductive history.

Women with one lifetime singleton pregnancy have increased risk of cardiovascular disease (CVD) mortality compared with women who continue reproduction particularly if the pregnancy had complications. Women with twins have higher risk of pregnancy complications, but CVD mortality risk in women with twin pregnancies has not been fully described. We estimated risk of long-term CVD mortality in women with naturally conceived twins compared to women with singleton pregnancies, accounting for lifetime number of pregnancies and pregnancy complications. Using linked data from the Medical Birth Registry of Norway and the Norwegian Cause of Death Registry, we identified 974,892 women with first pregnancy registered between 1967 and 2013, followed to 2020. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for maternal CVD mortality were estimated by Cox regression for various reproductive history (exposure categories): (1) Only one twin pregnancy, (2) Only one singleton pregnancy, (3) Only two singleton pregnancies, (4) A first twin pregnancy and continued reproduction, (5) A first singleton pregnancy and twins in later reproduction and (6) Three singleton pregnancies (the referent group). Exposure categories were also stratified by pregnancy complications (pre-eclampsia, preterm delivery or perinatal loss). Women with one lifetime pregnancy, twin or singleton, had increased risk of CVD mortality (adjusted hazard [HR] 1.72, 95% confidence interval [CI] 1.21, 2.43 and aHR 1.92, 95% CI 1.78, 2.07, respectively), compared with the referent of three singleton pregnancies. The hazard ratios for CVD mortality among women with one lifetime pregnancy with any complication were 2.36 (95% CI 1.49, 3.71) and 3.56 (95% CI 3.12, 4.06) for twins and singletons, respectively. Women with only one pregnancy, twin or singleton, had increased long-term CVD mortality, however highest in women with singletons. In addition, twin mothers who continued reproduction had similar CVD mortality compared to women with three singleton pregnancies.

Associations of Dietary Fats with All-Cause Mortality and Cardiovascular Disease Mortality among Patients with Cardiometabolic Disease.

Previous studies have shown distinct associations between specific dietary fats and mortality. However, evidence on specific dietary fats and mortality among patients with cardiometabolic disease (CMD) remains unclear. The aim of this study was to estimate the association between consumption of specific fatty acids and survival of patients with CMD and examine whether cardiometabolic biomarkers can mediate the above effects. The study included 8537 participants with CMD, from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Cox proportional hazards regression, restricted cubic spline regression, and isocaloric substitution models were used to estimate the associations of dietary fats with all-cause mortality and cardiovascular disease (CVD) mortality among participants with CMD. Mediation analysis was performed to assess the potential mediating roles of cardiometabolic biomarkers. During a median follow-up of 10.3 years (0–27.1 years), 3506 all-cause deaths and 882 CVD deaths occurred. The hazard ratios (HRs) of all-cause mortality among patients with CMD were 0.85 (95% confidence interval (CI), 95% CI, 0.73–0.99; p trend = 0.03) for ω-6 polyunsaturated fatty acids (ω-6 PUFA), 0.86 (95% CI, 0.75–1.00; p trend = 0.05) for linoleic acid (LA), and 0.86 (95% CI, 0.75–0.98; p trend = 0.03) for docosapentaenoic acid (DPA). Isocalorically replacing energy from SFA with PUFA and LA were associated with 8% and 4% lower all-cause mortality respectively. The HRs of CVD mortality among CMD patients comparing extreme tertiles of specific dietary fats were 0.60 (95% CI, 0.48–0.75; p trend = 0.002) for eicosapentaenoic acid (EPA), and 0.64 (95% CI, 0.48–0.85; p trend = 0.002) for DPA and above effects were mediated by levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), and high density lipoprotein cholesterol (HDL). Restricted cubic splines showed significant negative nonlinear associations between above specific dietary fats and mortality. These results suggest that intakes of ω-6 PUFA, LA, and DPA or replacing SFA with PUFA or LA might be associated with lower all-cause mortality for patients with CMD. Consumption of EPA and DPA could potentially reduce cardiovascular death for patients with CMD, and their effects might be regulated by cardiometabolic biomarkers indirectly. More precise and representative studies are further needed to validate our findings.

Serum total indoxyl sulfate levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study

BackgroundThe association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD).MethodsA prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the “X-tile” program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality.ResultsDuring a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01–1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10–2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable.ConclusionThe serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.

Associations of Serum Folate and Vitamin B12 Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes

The associations of serum folate and vitamin B12 levels with cardiovascular outcomes among patients with type 2 diabetes (T2D) remain unclear. To investigate the associations of serum folate and vitamin B12 levels with risk of cardiovascular disease (CVD) mortality among individuals with T2D. This prospective cohort study included 8067 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2014 and NHANES III (1988-1994). American Diabetes Association criteria were used to define T2D. Data were analyzed between October 1, 2020, and April 1, 2021. Serum folate and vitamin B12 levels. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of serum folate and vitamin B12 levels with risks of CVD and all-cause mortality. Two multivariable models were constructed. Restricted cubic spline analyses were used to examine the nonlinear association of serum folate levels and vitamin B12 levels with CVD mortality, and nonlinearity was assessed using the likelihood ratio test. This cohort study included data from 7700 participants in the folate analysis (mean [SE] age, 57.8 [0.3] years; 3882 men [weighted, 50.5%]; median serum folate level, 12.1 ng/mL [IQR, 7.1-19.5 ng/mL]) and 4860 participants for the vitamin B12 analysis (mean [SE] age, 57.8 [0.3] years; 2390 men [weighted, 50.7%]; median serum vitamin B12 level, 506.1 pg/mL [IQR, 369.1-703.5 pg/mL]). During 72 031 person-years of follow-up, 799 CVD deaths were documented for the folate analysis, and during 43 855 person-years of follow-up, 467 CVD deaths were reported for the vitamin B12 analysis. Nonlinear associations were observed for serum levels of folate (P = .04 for nonlinearity) and vitamin B12 (P = .04 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the second quartile of serum folate levels (7.1-12.1 ng/mL), the hazard ratios for CVD mortality were 1.43 (95% CI, 1.04-1.98) for participants in the lowest serum folate level quartile (<7.1 ng/mL) and 1.03 (95% CI, 0.74-1.44) for participants in the highest quartile (≥19.5 ng/mL). In addition, compared with participants in the second quartile of serum vitamin B12 levels (369.1-506.0 pg/mL), the hazard ratios for CVD mortality were 1.74 (95% CI, 1.20-2.52) for participants in the lowest quartile (<369.1 pg/mL) and 2.32 (95% CI, 1.60-3.35) for participants in the highest quartile (≥703.5 pg/mL). Similar patterns of association were observed for all-cause mortality (nonlinearity: P = .01 for folate and P = .02 for vitamin B12). This cohort study found that both low and high serum levels of vitamin B12 as well as low serum levels of folate were significantly associated with higher risk of CVD mortality among individuals with T2D.

Fresh fruit consumption, physical activity, and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study

Background and aimsWe explored the associations among fruit consumption, physical activity, and their dose–response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. Methods and resultsWe prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21–94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose–response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64–0.88), CVD mortality (HR 0.69, 0.51–0.94) and stroke mortality (HR 0.57, 0.36–0.89), but not with heart disease mortality (HR 0.93, 0.56–1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37–0.53) for all-cause mortality, 0.46 (0.33–0.64) for CVD mortality, 0.46 (0.29–0.74) for stroke mortality and 0.51 (0.29–0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. ConclusionsFruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.

Serum Uric Acid Revealed a U-Shaped Relationship With All-Cause Mortality and Cardiovascular Mortality in High Atherosclerosis Risk Patients: The ASSURE Study.

Background: Previous studies have demonstrated an association between hyperuricemia and cardiovascular disease (CVD). The Framingham study confirmed that patients with high atherosclerotic risks (HARs) had worse prognoses. However, after adjusting for confounding factors, the association between serum uric acid (SUA) and all-cause mortality and cardiovascular mortality remains unclear, especially for HAR patients.Objective: The aim of this study was to reveal the relationship of SUA with all-cause and cardiovascular mortality in HAR patients.Methods: This multicenter cohort study enrolled 3,047 participants, and the follow-up was 68.85 ± 11.37 months. Factors related to cardiovascular and all-cause mortality were tested by multivariate Cox regression analysis. Restricted cubic splines (RCSs) with knots were used to explore the shape of the dose–response relationship with SUA and the hazard ratio (HR) of all-cause and CVD mortality. SUA transformed by RCS was added to the Cox regression model as an independent variable, and all-cause and CVD mortality scores were calculated. Survival receiver operating characteristic curves were produced using a regression model predicting the score.Results: SUA demonstrated a “U-shaped” relationship with all-cause and cardiovascular mortality. SUA predicted all-cause and CVD mortality, with cutoff values of values of >370.5 μmol/L for males and >327.65 μmol/L for females and <180.5 μmol/L for males and <165.7 μmol/L for females, respectively. The survival ROC curve indicated that SUA is able to predict all-cause and CVD mortality, with areas under the curve of 0.702 and 0.711, respectively. The HRs of all-cause mortality (male and female) with hyperuricemia and hypouricemia were 2.08 and 2.01 and 2.04 and 1.98, respectively, and the HRs of CVD mortality (male and female) were 2.09 and 1.79, and 2.02 and 1.89, respectively.Conclusion: Abnormal SUA levels were significant and independent risk factors for all-cause and CVD mortality. Hyperuricemia and hypouricemia increased mortality in both males and females. Routine SUA evaluation and intensive management are needed for HAR patients.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03616769.

A nonlinear association of total cholesterol with all-cause and cause-specific mortality

BackgroundThe link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality.MethodsAll data analyzed were obtained from the National Health and Nutrition Examination Survey 1999–2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan–Meier survival curve and subgroup analyses were conducted.ResultsThe sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18–65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group.ConclusionsA nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project

BackgroundChronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.MethodsThe present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality.ResultsThe overall prevalence of CKD stage 3–5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts.ConclusionCKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution.

COMPARISON OF A FRAILTY INDEX WITH CARDIOVASCULAR RISK SCORES IN PREDICTING CARDIOVASCULAR DISEASE MORTALITY

We compared the predictive and discriminative ability of frailty with traditional cardiovascular risk scores to estimate 10-year cardiovascular disease (CVD) mortality risk. Individuals aged 20-79 years old from the National Health and Nutrition Examination Survey who were free from CVD were included (n= 32,066). A 33-item frailty index (FI) which excluded CVD and diabetes-related variables was calculated. We calculated the Framingham Disease Risk (FDR) Hard Coronary Heart Disease and General CVD risk scores, the American Heart Association/American College of Cardiology (AHA/ACC) atherosclerotic cardiovascular disease risk equation, and the European Systematic Coronary Risk Estimation tool. A total of 322 individuals died (1.0%) from CVD. There was a low correlation between the FI and CVD risk scores (spearman’s r= 0.19-0.33; p<0.0001) and a weak to strong correlation between CVD risk scores (spearman’s r=0.19-0.88; p<0.0001). The competing-risks hazard ratio for CVD mortality for every 1% increase in the FI was 1.040 (95% CI: 1.032-1.048; p<0.0001) in an age and sex-adjusted model. The FI was independently predictive of CVD mortality when the other CVD risk scores were added to the model. The area under the receiving operating characteristic (ROC) curve was 0.800 (95% CI: 0.789-0.808; p<0.0001) for the FI. ROC values for the CVD risk scores ranged from 0.710 (95% CI: 0.700-0.721; p<0.0001) for the AHA/ACC risk score to 0.779 (95% CI: 0.770-0.789; p<0.0001) for the FDR General CVD risk score. An FI calculated with non-CVD and diabetes variables can predict 10-year CVD mortality risk independently of traditional CVD risk scores.