Higher Risk Of Cardiovascular Disease Death Research Articles

Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study

BackgroundHigher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes.MethodsA total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes.ResultsFractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20–6.22).ConclusionsElevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.

Cholesterol paradox in the community-living old adults: is higher better?

To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Pregnancy complications in last pregnancy and mothers’ long-term cardiovascular mortality: does the relation differ from that of complications in first pregnancy? A population-based study

BackgroundWomen who experience complications in first pregnancy are at increased risk of cardiovascular disease (CVD) later in life. Little corresponding knowledge is available for complications in later pregnancies. Therefore, we assessed complications (preeclampsia, preterm birth, and offspring small for gestational age) in first and last pregnancies and the risk of long-term maternal CVD death, taking women´s complete reproduction into account.Data and methodsWe linked data from the Medical Birth Registry of Norway to the national Cause of Death Registry. We followed women whose first birth took place during 1967–2013, from the date of their last birth until death, or December 31st 2020, whichever occurred first. We analysed risk of CVD death until 69 years of age according to any complications in last pregnancy. Using Cox regression analysis, we adjusted for maternal age at first birth and level of education.ResultsWomen with any complications in their last or first pregnancy were at higher risk of CVD death than mothers with two-lifetime births and no pregnancy complications (reference). For example, the adjusted hazard ratio (aHR) for women with four births and any complications only in the last pregnancy was 2.85 (95% CI, 1.93–4.20). If a complication occurred in the first pregnancy only, the aHR was 1.74 (1.24–2.45). Corresponding hazard ratios for women with two births were 1.82 (CI, 1.59–2.08) and 1.41 (1.26–1.58), respectively.ConclusionsThe risk for CVD death was higher among mothers with complications only in their last pregnancy compared to women with no complications, and also higher compared to mothers with a complication only in their first pregnancy.

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study.

Background and aim: For a long time, aspirin has been recommended for the prevention of cardiovascular disease (CVD). However, results of long-term effects of aspirin use on the risk of CVD and all-cause death as well as cause-specific mortality are not consistent. This study aims to investigate the relationship between low- or high-dose preventive aspirin use and the risk of death from all-cause, CVD, and cancer among US adults aged 40years and older. Methods: A prospective cohort study was conducted by utilizing four cycles of the National Health and Nutrition Examination Survey (NHANES) and linked 2019 mortality files. Cox proportional hazard models accounting for multiple covariates were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for the associations between low- or high-dose aspirin use and risk of death. Results: A total of 10,854 individuals (5,364 men and 5,490 women) were enrolled in the study. During a median follow-up of 4.8years, 924 death events including 294 CVD death and 223 cancer death were documented. We found no evidence that taking low-dose aspirin decreased the chance of dying from any cause (HR: 0.92, 95% CI: 0.79-1.06), CVD (HR: 1.03, 95% CI: 0.79-1.33), or cancer (HR: 0.80, 95% CI: 0.60-1.08). High-dose aspirin users had a higher risk of CVD death compared to participants who had never used aspirin (HR: 1.63, 95% CI: 1.11-2.41). Conclusion: Using low-dose aspirin has no effect on the risk of death from any causes, whereas taking high doses of aspirin increases the risk of CVD death.

Risk of Cardiovascular Disease Death in Older Malignant Melanoma Patients: A Population-Based Study.

Simple SummaryStudies have shown that the risk of cardiovascular disease (CVD) death is significantly increased in older (65 or older) malignant melanoma (MM) patients. Proportion of death, standardized mortality ratio (SMR) and cumulative mortality were used to compare the differences in mortality between MM and CVD in older MM patients. Our study revealed older MM patients died from diseases other than primary cancer, and CVD was the leading cause. MM patients had a 1.98-fold higher risk of CVD death than the general population, which signals the importance of prevention and treatment of cardiovascular disease in patients with MM.Noncancer deaths account for a large proportion of deaths in patients with malignant melanoma (MM), but the risk of cardiovascular disease (CVD) death in older MM patients remains unclear. This study aimed to estimate the risk of CVD death in older MM patients. Data on older MM patients were obtained in the Surveillance, Epidemiology, and End Results database. Risk of CVD death was calculated by standardized mortality rates (SMRs), cumulative mortality and proportion of different causes of death. MM patients had a higher risk of CVD death than general populations (SMR = 1.98; 95% CI 1.93–2.03, p < 0.001). CVD death was more common in MM patients who were diagnosed at age 85 or older, had a localized stage, were white, had surgical treatment, had a primary head/neck/upper limb site and had a low-grade and superficial spreading/lentigo malignant pathologic type. Cumulative CVD mortality was more common than primary cancer in all older age groups, male or female, and patients with localized-stage disease. Other than primary cancer, CVD was the main cause of death in older patients diagnosed with MM. Our findings highlight CVD death is an important competing event of deaths in older MM patients, and more attention should be paid to reducing CVD death to improve survival.

Α higher ratio of serum uric acid to serum creatinine could predict the risk of total and cause specific mortality- insight from a US national survey

IntroductionThe link between serum uric acid to serum creatinine ratio (SUA/SCr) and mortality has not been studied yet. MethodsWe prospectively evaluated the association between SUA/SCr and risk of total and cause specific [cardiovascular disease (CVD) and cancer] mortality by applying on the National Health and Nutrition Examination Surveys (NHANES, 1999–2010). Vital status through December 31, 2011 was ascertained. Adjusted Cox proportional hazard regression models were performed to determine the links between SUA/SCr and mortality. ResultsOverall, 20,209 individuals were included (mean age = 47.5 years, 48.9% men) and 3523 deaths occurred during the 76.4 months of follow-up. In a fully adjusted model, individuals in the fourth (Q4) and third (Q3) quartile of SUA/SCr had a 44 and 35% greater risk of total mortality [risk ratio (RR): 1.44 (95% confidence interval, 95%CI: 1.05–1.98) and 1.35 (1.10–1.66), respectively], as well as a 69 and 47% higher risk of CVD death [RR: 1.69 (1.09–2.62) and 1.47 (1.14–1.89), respectively] compared with the lowest (Q1) quartile. With regard to SUA/SCr and cancer mortality, a significant association was found only between participants in Q4 and those in Q1 [RR: 1.12 (1.06–1.19)] in the partially adjusted model, whereas this relationship became non-significant after further adjustments [RR: 1.15 (0.96–1.39)]. ConclusionsThis is the first time that SUA/SCr has been associated with total and cause specific mortality in a large, representative sample of US adults. Further studies are needed to confirm these findings and establish their clinical implications.

Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease.

The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort. The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non-HDL-C with CVD mortality were tested with Cox proportional hazards models. In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1-1.7), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1), respectively. In multivariable-adjusted models using non-HDL-C <130 mg/dL as the reference, non-HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non-HDL-C with CVD mortality. In a low 10-year risk cohort with long-term follow-up, LDL-C and non-HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms.

Menopause Characteristics, Total Reproductive Years, and Risk of Cardiovascular Disease Among Chinese Women.

Previous studies, mostly of Western women, have reported inconsistent findings on the association of menopause characteristics (status, age, and time since menopause) and total reproductive years with risk of cardiovascular disease (CVD). The China Kadoorie Biobank recruited 302 632 women in 2004 to 2008 from 10 regions across China. During 9-year follow-up, 19 393 incident cases of stroke, 18 611 of ischemic heart disease, and 4978 CVD deaths occurred. Cox regression yielded adjusted hazard ratios relating each menopause characteristic and total reproductive years to CVD risk. Among 274 233 women with no prior CVD at baseline, 134 010 were naturally postmenopausal women (mean [SD] age at menopause of 48.6 [4.0] years and total reproductive years 32.7 [4.4]). Compared with premenopausal women, naturally peri- or postmenopausal women were at a higher risk of either fatal or nonfatal CVD. Among women who had had menopause, inverse associations were observed between age at menopause and risks of CVD mortality, incident ischemic heart disease, stroke, and subtypes of stroke, with 1.5% higher risk of CVD death (P<0.001), 0.7% for incident ischemic heart disease (P=0.002), and 0.5% for incident stroke (P=0.02) for every 1 year lower age at menopause. Compared with women who had menopause at age 48 to 50 years, lower age at menopause (ie, <43 years) was associated with 14% higher risk of CVD death and 6% higher risks of both incident ischemic heart disease and stroke. Higher risks of both fatal and nonfatal CVD were also found in women with 5 to 10, 10 to 15, 15 to 20, or >20 years since menopause compared with <5 years since menopause. Total reproductive years were inversely associated with risks of both fatal and nonfatal CVD, with 1.4% lower risk of CVD death per additional reproductive year (P<0.001). Women with younger age at menopause, longer time since menopause, or fewer total reproductive years had a higher risk of CVD.

Abstract 11655: Long Term Cardiovascular Mortality After Radiotherapy for Breast Cancer: A Meta-Analysis

Introduction: Cardiovascular disease (CVD) is a late complication of radiotherapy (RT); the mean cardiac dose from irradiation of a left-sided breast cancer is much higher than that for a right-sided breast cancer. However, there is limited knowledge regarding the long-term risk of RT on CVD mortality. This study sought to investigate the use of RT for breast cancer and its association with CVD mortality, in the context of the laterality of breast cancer. Hypothesis: Long term cardiac mortalty with left-sided breast cancer radiotherapy is much higher than that for a right-sided breast cancer. Methods: Databases were searched from their inception through December 2013. Studies reporting CVD mortality with left versus right sided breast RT were included. Two authors reviewed the studies, abstracted the data and checked for accuracy, quality and strength of evidence. The outcome of interest was CVD mortality. We calculated summary risk ratio (RR) and 95% confidence intervals (CI) with the random effects model. Results: The analysis included 289,109 patients from 13 observational studies. Women, who had received RT for left-sided breast cancer, had a higher risk of CVD death than those who received RT for a right-sided breast cancer (RR 1.12, 95% CI: 1.07 to 1.18). Difference in CVD mortality between left versus right breast RT was more apparent after 15 years of follow up (RR 1.23, 95% CI: 1.08 to 1.41). Conclusions: Mortality from CVD with left sided RT was significantly higher compared to right sided RT for breast cancer; this difference was more apparent after at least 15 years of follow up.

Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus

The prognostic utility of the ankle-brachial index (ABI) may be hampered in persons with diabetes due to peripheral arterial stiffening in the ankles. Stiffening of toe arteries occurs infrequently in diabetes. We aimed to determine the nature of the relationship of the toe-brachial index (TBI) and ABI with cardiovascular disease (CVD) mortality and to determine whether the associations are modified in individuals with diabetes. Individuals with clinically suspected atherosclerotic peripheral arterial disease who underwent ABI and TBI measurements in a vascular laboratory were monitored longitudinally for CVD mortality. Among 469 participants (89% men), the mean age was 68 ± 9 years, and 36% had diabetes. The mean ABI was 0.83 ± 0.28 and the mean TBI was 0.60 ± 0.24. During median 7.0 years of follow-up, there were 158 CVD deaths. The association of the ABI categories with CVD deaths differed in diabetic vs nondiabetic participants (P = .002 for interaction). In contrast, the association of the TBI categories with CVD deaths was similar, irrespective of diabetes status (P = .17 for interaction). Among diabetic patients, a U-shaped relationship was observed between ABI categories and CVD death: those with low (<0.90) and high (>1.30) ABIs were both at higher risk than those with normal ABIs (range, 0.90-1.30). In nondiabetic patients, association of ABI categories with CVD death was linear, such that those with an ABI >1.30 were at the lowest risk, whereas those with an ABI <0.90 were at higher risk. In contrast, the association of TBI categories with CVD death was linear irrespective of diabetes status. High TBI categories consistently predicted low risk, whereas risk was higher with progressively lower TBI categories. Among diabetic individuals with clinically suspected peripheral arterial disease, those with low and high ABIs are both at higher risk of CVD death. In contrast, a linear relationship was observed between TBI categories and CVD death irrespective of diabetes status. These findings suggest that stiffened ankle arteries may limit the predictive value of the ABI in individuals with diabetes, a limitation that may be overcome by measurement of the TBI.

Exercise Blood Pressure and Future Cardiovascular Death in Asymptomatic Individuals

Individuals with exaggerated exercise blood pressure (BP) tend to develop future hypertension. It is controversial whether they have higher risk of death from cardiovascular disease (CVD). A total of 6578 asymptomatic Lipid Research Clinics Prevalence Study participants (45% women; mean age, 46 years; 74% with untreated baseline BP <140/90 mm Hg [nonhypertensive]) performing submaximal Bruce treadmill tests were followed for 20 years (385 CVD deaths occurred). Systolic and diastolic BP at rest, Bruce stage 2, and maximal BP during exercise were significantly associated with CVD death. When we compared multivariate hazard ratios and 95% confidence intervals per 10/5-mm Hg BP increments, the association was strongest for rest BP (systolic, 1.21 [1.14 to 1.27]; diastolic, 1.20 [1.14 to 1.26]), then Bruce stage 2 BP (systolic, 1.09 [1.04 to 1.14]; diastolic, 1.09 [1.05 to 1.13]), then maximal exercise BP (systolic, 1.06 [1.01 to 1.10]; diastolic, 1.04 [1.01 to 1.08]). Overall, exercise BP was not significant after adjustment for rest BP. However, hypertension status modified the risk associated with exercise BP (P(interaction)=0.03). Among nonhypertensives, whether they had normal BP (<120/80 mm Hg) or prehypertension, Bruce stage 2 BP >180/90 versus < or =180/90 mm Hg carried increased risk independent of rest BP and risk factors (adjusted hazard ratio for systolic, 1.96 [1.40 to 2.74], P<0.001; diastolic, 1.48 [1.06 to 2.06], P=0.02) and added predictive value (net reclassification improvement, systolic, 12.0% [-0.1% to 24.2%]; diastolic, 9.9% [-0.3% to 20.0%]; relative integrated discrimination improvement, 14.3% and 12.0%, respectively). In asymptomatic individuals, elevated exercise BP carried higher risk of CVD death but became nonsignificant after accounting for rest BP. However, Bruce stage 2 BP >180/90 mm Hg identified nonhypertensive individuals at higher risk of CVD death.