Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems

DNA is subjected to many endogenous and exogenous damages. All organisms have developed a complex network of DNA repair mechanisms. A variety of different DNA repair pathways have been reported: direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and recombination repair pathways. Recent studies of the fundamental mechanisms for DNA repair processes have revealed a complexity beyond that initially expected, with inter- and intrapathway complementation as well as functional interactions between proteins involved in repair pathways. In this paper we give a broad overview of the whole DNA repair system and focus on the molecular basis of the repair machineries, particularly in Thermus thermophilus HB8

Age-Dependent Association Between Modifiable Risk Factors and Incident Cardiovascular Disease

BACKGROUND: There have been limited data examining the age-dependent relationship of wide-range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age-related associations between modifiable risk factors and the incidence of CVD. METHODS AND RESULTS: We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age cat-egory. Over a mean follow-up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years. CONCLUSIONS: The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.</p

Association of Cardiovascular Health Metrics With Risk of Transition to Hypertension in Non-Hypertensive Young Adults

BACKGROUND The risk of developing hypertension in young adults and its relationship to modifiable lifestyle factors are unclear. We aimed to examine the association of cardiovascular health (CVH) metrics with the risk of hypertension. METHODS We analyzed 66,876 participants aged 20-39 years, with available blood pressure (BP) data for 5 consecutive years, who had normal or elevated BP at the initial health check-up, enrolled in the JMDC Claims Database. Ideal CVH metrics included nonsmoking, body mass inde

Reduction in blood pressure for elevated blood pressure/stage 1 hypertension according to the American College of Cardiology/American Heart Association guideline and cardiovascular outcomes

Aims Few studies have examined the relationship of blood pressure (BP) change in adults with elevated BP or stage 1 hypertension according to the American College of Cardiology (ACC)/American Heart Association (AHA) guideline with cardiovascular outcomes. We sought to identify the effect of BP change among individuals with elevated BP or stage 1 hypertension on incident heart failure (HF) and other cardiovascular diseases (CVDs). Methods We conducted a retrospective cohort study including 616 483 individuals (median age 46 years, 73.7% men) with elevated and results BP or stage 1 hypertension based on the ACC/AHA BP guideline. Participants were categorized using BP classification at one-year as normal BP (n = 173 558), elevated BP/stage 1 hypertension (n = 367 454), or stage 2 hypertension (n = 75 471). The primary outcome was HF, and the secondary outcomes included (separately) myocardial infarction (MI), angina pectoris (AP), and stroke. Over a mean follow-up of 1097 ± 908 days, 10 544 HFs, 1317 MIs, 11 070 APs, and 5198 strokes were recorded. Compared with elevated BP/stage 1 hypertension at one-year, normal BP at one-year was associated with a lower risk of developing HF [hazard ratio (HR): 0.89, 95% CI:0.85–0.94], whereas stage 2 hypertension at one-year was associated with an elevated risk of developing HF (HR:1.43, 95% CI:1.36–1.51). This association was also present in other cardiovascular outcomes including MI, AP, and stroke. The relationship was consistent in all subgroups stratified by age, sex, baseline BP category, and overweight/obesity. Conclusion A one-year decline in BP was associated with the lower risk of HF, MI, AP, and stroke, suggesting the importance of lowering BP in individuals with elevated BP or stage 1 hypertension according to the ACC/AHA guideline to prevent the risk of developing CVD.</p